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1. Introduction 1
Who should use this documentation 2
What can simulation engines do? 2
Energy minimization 2
Molecular dynamics 3
Other forcefield-based calculations 3
What are forcefields and simulation engines? 4
Using this guide 5
Additional information 6
Typographical conventions 7
2. Forcefields 9
The potential energy surface 10
Empirical fit to the potential energy surface 11
The forcefield 12
The energy expression 16
Forcefields supported by MSI forcefield engines 19
Main types of forcefields 20
Advantages of having several forcefields 23
Primary uses of each MSI forcefield 24
Second-generation forcefields accurate for many properties 26
CFF91, PCFF, CFF, COMPASS—consistent forcefields 28
MMFF93, the Merck molecular forcefield 34
Rule-based forcefields broadly applicable to the periodic table
35
ESFF, extensible systematic forcefield 36
UFF, universal forcefield 42
VALBOND 44
Dreiding forcefield 51
Classical forcefields 53
AMBER forcefield 53
CHARMm forcefield 56
CVFF, consistent valence forcefield 57
Special-purpose forcefields 61
Glass forcefield 62
MSXX forcefield for polyvinylidene fluoride 64
Zeolite forcefields 65
Forcefields for sorption on zeolites 67
Forcefields for Cerius2•Morphology module 67
Archived and untested forcefields 68
4. Minimization 153
General minimization process 155
Specific minimization example 155
Line search 157
Minimization algorithms 160
Steepest descents 161
Conjugate gradient 164
Newton–Raphson methods 166
General methodology for minimization 173
Minimizations with MSI simulation engines 174
When to use different algorithms 176
Convergence criteria 178
Significance of minimum-energy structure 180
Energy and gradient calculation 181
Vibrational calculation 182
Application of minimization to vibrational theory 183
Vibrational frequencies 185
General methodology for vibrational calculations 187
A. References 273
Energy minimization
Typical uses of energy minimization include:
♦ Optimizing initial geometries of models constructed in a
molecular modeling program such as Cerius2™ or Insight®.
♦ Repairing poor geometries occurring at splice points during
homology building of protein structures.
♦ Mapping the energy barriers for geometric distortions and con-
formational transitions using “torsion forcing” to obtain Ram-
achandran-type contour plots for proteins or RIS statistical
weights for polymers.
Molecular dynamics
Typical uses of molecular dynamics include:
♦ Searching the conformational space of alternative amino acid
sidechains in site-specific mutation studies.
♦ Identifying likely conformational states for highly flexible
polymers or for flexible regions of macromolecules such as pro-
tein loops.
♦ Producing sets of 3D structures consistent with distance and
torsion constraints deduced from NMR experiments (simu-
lated annealing).
♦ Calculating free energies of binding, including solvation and
entropy effects.
♦ Probing the locations, conformations, and motions of mole-
cules on catalyst surfaces.
♦ Running diffusion calculations.
Additional information
Available documentation Guides are available for every simulation engine and modeling
program that MSI provides, including these:
♦ MSI Forcefield Engines: CDiscover.
♦ Cerius2 Forcefield Engines: OFF.
♦ MSI Forcefield Engines: FDiscover.
♦ MSI Forcefield Engines: CHARMm.
♦ Cerius2 Modeling Environment.
♦ Insight II.
♦ QUANTA documentation set.
On-screen help In addition to the task-oriented documentation for each simula-
tion engine, on-screen help is available within the Cerius2, Insight,
and QUANTA environments. Please see the documentation for the
specific program for how to access the help.
Supplemental documen- Additional information on using the Cerius2, Insight, and
tation QUANTA interfaces, including building models and writing
scripts for automated running, is contained in their respective
guides. Technical information that is mainly of use to program-
mers and system administrators is contained in installation/
administration guides. Supplemental information that may be of
general interest (including additional information on the elec-
tronic documentation) is contained in release notes.
MSI’s website The URL for the documentation and customer support areas of
MSI’s website are :
http://www.msi.com/doc/
http://www.msi.com/support/
Information relevant to forcefields, simulation engines, and mod-
eling programs can be found.
Typographical conventions
Unless otherwise noted in the text, Forcefield-Based Simulations uses
these typographical conventions:
♦ Terms introduced for the first time are presented in italic type.
For example:
Instructions are given to the software via control panels.
♦ Keywords in the interface are presented in bold type. In addi-
tion, slashes (/) are used to separate a menu item from a sub-
menu item. For example:
Select the View/Colors… menu item means to click the View
menu item, drag the cursor down the pulldown menu that
appears, and release the mouse button over the Colors… item.
♦ Words you type or enter are presented in bold type. For exam-
ple:
Enter 0.001 in the Convergence entry box.
♦ UNIX command dialog and file samples are represented in a
typewriter font. For example, the following illustrates a line
in a .grf file:
CERIUS Grapher File
In this example, the name of the file from which data are read
in replaces input_file.
Related information Preparing the Energy Expression and the Model presents information
on how the functional forms of forcefields are used for real simu-
lations. You need to read it to optimize how you set up your sim-
ulation. The general procedure for forcefield-based calculations is
outlined under Using forcefields.
The atom types defined for each forcefield are listed under Force-
field Terms and Atom Types. Illustrations of various types of cross
terms are also included.
The files that specify the forcefields are described in the separate
documentation for each simulation engine.
2
dV d R
– = m 2 Eq. 4
dR dt
Molecular dynamics and The solution of Eq. 4 using an empirical fit to the potential energy
mechanics surface E(R) is called molecular dynamics. Molecular mechanics
ignores the time evolution of the system and instead focuses on
finding particular geometries and their associated energies or
other static properties. This includes finding equilibrium struc-
tures, transition states, relative energies, and harmonic vibrational
frequencies.
The forcefield
Components of a force- The forcefield contains the necessary building blocks for the calcu-
field lations of energy and force:
♦ A list of atom types.
♦ A list of atomic charges (if not included in the atom-type infor-
mation).
♦ Atom-typing rules.
♦ Functional forms for the components of the energy expression.
♦ Parameters for the function terms.
♦ For some forcefields, rules for generating parameters that have
not been explicitly defined.
♦ For some forcefields, a defined way of assigning functional
forms and parameters.
This total “package” for the empirical fit to the potential energy
surface is the forcefield.
Coordinates, terms, func- The forcefields commonly used for describing molecules employ a
tional forms combination of internal coordinates and terms (bond distances, bond
angles, torsions, etc.), to describe part of the potential energy sur-
face due to interactions between bonded atoms, and nonbond terms
to describe the van der Waals and electrostatic (etc.) interactions
between atoms. The functional forms range from simple quadratic
forms to Morse functions, Fourier expansions, Lennard–Jones
potentials, etc.
3.0 3.0
0.0 0.0
-2 2 -2 2
Figure 1. Energy and probability of a mechanical and quantum particle
in a harmonic energy well
The energy is indicated by the heavy lines and probability by the thin lines. The
total energy of the system is indicated by the pale horizontal line. The classical
(mechanical) probability is highest when the particle reaches it maximum
potential energy (zero velocity) and drops to zero between these points. The
quantum mechanical probability is highest where the potential energy is low-
est, and there is a finite probability that the particle can be found outside the
classical limits (pale vertical lines).
and use, see Preparing the Energy Expression and the Model in this
documentation set and also the documentation for the particular
simulation engine.
Example energy expres- As a simple example of a complete energy expression, consider the
sion for water following equation, which might be used to describe the potential
energy surface of a water model:
0 2 0 2 0 2
V ( R ) = K oh ( b – b oh ) + K oh ( b′ – b oh ) + K hoh ( θ – θ hoh ) Eq. 7
where Koh, b0oh, Khoh, and θ0hoh are parameters of the forcefield, b is
the current bond length of one O–H bond, b′ is the length of the
other O–H bond, and θ is the H–O–H angle.
In this example, the forcefield defines:
♦ The coordinates to be used (bond lengths and angles).
♦ The functional form (a simple quadratic in both types of coor-
dinates).
♦ The parameters (the force constants Koh and Khoh, as well as the
reference values b0oh and θ0hoh).
The reference O–H bond length and reference H–O–H angle are
the values for an ideal O–H bond and H–O–H angle at zero
energy, which is not necessarily the same as their equilibrium
values in a real water molecule.
Example forcefield func- Eq. 7 is an example of an energy expression as set up for a simple
tion molecule. Eq. 8 is an example of the corresponding general,
summed forcefield function:
V(R) =
∑ D [1 – exp(–a(b – b )) ] + ∑ H ( θ – θ ) + ∑ H [ 1 + s cos ( nφ) ]
b 0
2
θ 0
2
φ
b θ φ
+
∑H χ + ∑∑F
χ
2
bb′ ( b – b 0 ) ( b′ – b′ 0 ) +
∑∑F θθ′ ( θ – θ 0 ) ( θ′ – θ′ 0 )
χ b b′ θ θ′
+
∑∑F bθ ( b – b0 ) ( θ – θ0 ) +
∑∑F θθ′φ ( θ – θ 0 ) ( θ′ – θ′ 0 ) cos φ
b θ θ θ′
∑∑ ∑∑
A ij B ij q i q j
+ F χχ′ χχ′ + ------- – ------ + ---------
r ij12 r ij6 r ij
χ χ′ i j>i
Eq. 8
The first four terms in this equation are sums that reflect the
energy needed to stretch bonds (b), bend angles (θ) away from
their reference values, rotate torsion angles (φ) by twisting atoms
about the bond axis that determines the torsion angle, and distort
planar atoms out of the plane formed by the atoms they are
bonded to (χ). The next five terms are cross terms that account for
interactions between the four types of internal coordinates. The
final term represents the nonbond interactions as a sum of repul-
sive and attractive Lennard–Jones terms as well as Coulombic
terms, all of which are a function of the distance rij between atom
pairs. The forcefield defines the functional form of each term in
this equation as well as the parameters such as Db, α, and b0. The
forcefield also defines internal coordinates such as b, θ, φ, and χ as
a function of the Cartesian atomic coordinates, although this is not
explicit in Eq. 8.
We should note that the energy expression in Eq. 8 is cast in a gen-
eral form. The true energy expression for a specific model includes
information about the coordinates that are included in each sum.
For example, it is common to exclude interactions between bonded
and 1–3 atoms in the summation representing the nonbond inter-
actions. Thus, a true energy expression might actually use a list of
allowed interactions rather than the full summation implied in
Eq. 8.
Forcefield Docu-
Type and use of forcefield name Simulation engine Forcefield filename(s) mented
Second-generation, CFF91 Discover; OFFa cff91.frc; cff91_950_ here
general-purpose 1.01
CFF95b Discover; OFF cff95.frc; cff95_950_ here
1.01
CFF Discover, OFF cff.frc; cff1.01 here
MMFF93 CHARMmc mmff_setup.STR here
2nd-generation, poly- PCFF, COM- Discover; OFF pcff.frc; pcff_300_1.01, here
mers PASS, compass.frc;
COMPASS COMPASS1.0,
982 compass98.frc;
Compass98.01
Rule-based, broadly ESFF Discoverd esff.frc here
applicable, general- Universal OFF UNIVERSAL1.02 here
purpose UFF-VAL- OFF UFF_VALBOND1.01 here
BOND
Dreiding OFF DREIDING2.21 here
Classical, general-pur- AMBER Discover, OFFe amber.frc here
pose (biochemistry) CHARMm CHARMmf here
CVFF Discover; OFF cvff.frc; cvff_950_1.01g here
Forcefield Docu-
Type and use of forcefield name Simulation engine Forcefield filename(s) mented
Special-purpose:
Inorganic oxide glasses Glass OFF glassff_1.01, glassff_ here
2.01
Morphology module of Lifson OFF morph_lifson1.11 here
Cerius2 Momany OFF morph_momany1.1 here
Scheraga OFF morph_scheraga1.1 here
Williams OFF morph_williams1.01 here
Polyvinylidene fluoride MSXX OFF msxx_1.01 here
polymers
Zeolites BKS OFF bks1.01 here
Burchart OFF burchart1.01 here
Burchart– OFF burchart1.01- here
Dreiding DREIDING2.21
Burchart– OFF burchart1.01- here
Universal UNIVERSAL1.02
CVFF_aug Discover; OFF cvff_300_1.01 here
Zeolite sorption Yashonath OFF sor_yashonath1.01 here
Demontis OFF sor_demontis1.01 here
Pickett OFF sor_pickett1.01 here
Watanabe– OFF watanabe-austin1.01 here
Austin
Older, archived, misc. several Discover; OFF gifts/*, archive/* here
Untested, misc. several OFF untested/ here
a
OFF = the Open Force Field module of Cerius2.
b
Marketed as an add-on forcefield, not present in Discover or OFF by default.
cCHARMm as run through the Cerius2•MMFF module, not in QUANTA or standard
CHARMm.
d 2
In CDiscover, not FDiscover; in other words, in the Cerius •Discover and the Insight•Discover_3 modules,
not the Insight•Discover module.
eIn the Insight•Discover_3 and the Insight•Discover modules but not the Cerius2•Discover module. An
older version of AMBER is accessible through the Cerius2•OFF module.
fCHARMm is both the name of a forcefield and the name of a simulation engine that handles the
CHARMm forcefield.
g
CVFF differs slightly in versions 3.0.0 and 95.0 of Insight II— both versions are included in Cerius2•OFF.
tively, you can click the Show information action button in the
Load Force Field control panel.
Additional information about forcefields included with Insight
4.0.0 can be obtained with the Forcefield/FF_Info parameter
block, which is accessed through the Builder and other modules.
(It is not included in Insight 97.0.)
Functional form
All the CFF forcefields (CFF91, CFF, PCFF, COMPASS) have the
same functional form, differing mainly in the range of functional
groups to which they were parameterized (and therefore, having
slightly different parameter values). These differences can be
examined by using the forcefield editing capabilities of Cerius2
and Insight or in the forcefield files. Atom equivalences for assign-
ment of parameters to atom types may also differ, as may some
combination rules for nonbond terms (see Preparing the Energy
Expression and the Model for explanation of these processes, which
occur during forcefield setup).
The analytic expressions used to represent the energy surface are
shown in Eq. 9. Both anharmonic diagonal terms and many cross-
terms are necessary for a good fit to a variety of structures and rel-
ative energies, as well as to vibrational frequencies.
The CFF forcefields employ quartic polynomials for bond stretch-
ing (Term 1) and angle bending (Term 2) and a three-term Fourier
expansion for torsions (Term 3). The out-of-plane (also called
inversion) coordinate (Term 4) is defined according to Wilson et al.
(1980). All the crossterms up through third order that have been
found to be important (Terms 5–11) are also included—this gives
a forcefield equivalent to the best used in a formate anion test case
(Maple et al. 1990). Term 12 is the Coulombic interaction between
the atomic charges, and Term 13 represents the van der Waals
interactions, using an inverse 9th-power term for the repulsive part
rather than the more customary 12th-power term.
No explicit special atom types are used for carbons in strained
three- and four-membered rings. The quartic angle potential, com-
bined with crossterms, enables accurate description of normal
Note
Because the Wilson out-of-plane definition is used in the CFF
family of forcefields, results calculated with CDiscover,
FDiscover, and Cerius2•OFF should agree exactly.
Eq. 9
∑ [K (b – b ) + K (b – b ) + K (b – b ) ]
2 0
2
3 0
3
4 0
4
b (1)
2(θ – θ0 ) 2 + H3 ( θ – θ0 ) 3 + H 4 ( θ – θ0 ) 4
(2)
(3)
χχ
2 +
∑∑F bb′ ( b – b 0 ) ( b′ – b′0 ) +
∑∑F θθ′ ( θ – θ 0 ) ( θ′ – θ
b b′ (5) θ θ′ (6)
∑F bθ ( b – b0 ) ( θ – θ0 ) +
∑ ∑ (b – b )[ V cos φ + V cos 2φ + V
0 1 2
θ (7) b φ (8)
φ (9)
φ (10)
∑∑ ∑ ∑
q i qj A ij B ij
K φθθ′ cos φ ( θ – θ 0 ) ( θ′ – θ′0 ) + --------- + ------ – ------
εr ij r ij9 r ij6
θ θ′ i>j i>j
(11) (12) (13)
CFF91 forcefield
Applicability CFF91 is useful for hydrocarbons, proteins, protein–ligand interac-
tions. For small models it can be used to predict: gas-phase geom-
etries, vibrational frequencies, conformational energies, torsion
barriers, crystal structures; for liquids: cohesive energy densities;
for crystals: lattice parameters, rms atomic coordinates, sublima-
tion energies; for macromolecules: protein crystal structures.
It has been parameterized explicitly (based on quantum mechan-
ics calculations and molecular simulations, see Parameterization)
for acetals, acids, alcohols, alkanes, alkenes, amides, amines, aro-
matics, esters, and ethers (Maple 1994a, Hwang 1994).
The functional form of CFF91 is exactly as shown in Eq. 9.
Atom types CFF91 has parameters for functional groups that consist of H, Na,
Ca, C, Si, N, P, O, S, F, Cl, Br, I, and/or Ar. The atom types of the
CFF91 forcefield are listed in Table 27.
Partial charges The bond increment section of the .frc file for CFF91 enables partial
charges to be determined whenever the Discover program or the
Cerius2•OFF module is able to assign automatic atom types.
CFF forcefield
Applicability CFF (formerly CFF95) was parameterized for additional func-
tional groups beyond CFF91 (Maple et al. 1994a, b, Hwang et al.
1994, Hagler & Ewig 1994). It is recommended for all life sciences
applications and for organic polymers such as polycarbonates and
polysaccharides.
Almost all types of computations within Insight or Cerius2 life sci-
ence modules may be performed using CFF. These include inter-
molecular and intramolecular energies and forces, optimization of
model structures, and molecular dynamics simulations. CFF is not
currently implemented for relative free-energy perturbations or
for applications in the Docking module of Insight.
Atom types The atom types of the CFF forcefield are listed in the separate doc-
umentation for CFF (below).
Additional information Additional information on CFF, which is sold as a separately
licensed product, is contained in the MSI Forcefields:CFF book
(published separately by MSI).
∑E + ∑E + ∑E
E MMFF = b ij a ijk ba ijk Eq. 10
+
∑E + ∑E + ∑E + ∑E
oop t vdW q
Where:
E Quartic bond stretching term.
bij
E Cubic angle bending term (cosine when the refer-
aijk ence angle is ≅180°).
E Stretch–bend crossterm.
baijk
E Term for out-of-plane motion at tri-coordinate cen-
oopijk;l ters, using the Wilson definition of the out-of-
plane angle.
E Torsion twisting term.
tijkl
E Buffered 14–7 van der Waals interaction term.
vdWij
E Buffered Coulombic term for electrostatic interac-
qij tions. Use of a distance-dependent dielectric
“constant” is supported.
Derivation
ESFF was derived using a mixture of DFT calculations on dressed
atoms to obtain polarizabilities, gas-phase and crystal structures,
etc. The training set included primarily organic and organometal-
lic compounds and a few inorganic compounds. The focus was on
crystal structures and sublimation energies. The training set
included models containing each element in the first 6 periods up
to lead (Z = 82) (except for the inert gases), Sr, Y, Tc, La, and the lan-
thinides (except for Yb).
Parameters and charges are generated on-the-fly, based on the
model configuration, the local environment, and the derived rules.
Functional form
Valence energy The analytic energy expressions for the ESFF forcefield are pro-
vided in Eq. 11. Only diagonal terms are included.
Bond energy The bond energy is represented by a Morse functional form, where
the bond dissociation energy D, the reference bond length r0, and
the anharmonicity parameters are needed. In constructing these
parameters from atomic parameters, the forcefield utilizes not
only the atom types and bond orders, but also considers whether
the bond is endo or exo to 3-, 4-, or 5-membered rings.
The rules themselves depend on the electronegativity, hardness,
and ionization of the atoms as well as atomic anharmonicities and
the covalent radii and well depths. The latter quantities are fit
parameters, and the former three are calculated.
∑
0 2
( –α ( rb – rb ) )
E pot = Db 1 – e
b K (1)
∑
---------------
a 0 2
- ( cos θ a – cos θ a )
0
sin θ a
2
(normal)
a
∑
2K a ( cos θ a + 1 ) (linear)
a
+
∑
θ (perpendicular)
K a a cos2 θ a
a
(equatorial)
∑
2K a ( – β ( r 13 – ρ a ) )
--------- ( 1 – cos ( nθ a ) ) + 2K a
n2 (2)
a
sin2 θ 1 sin2 θ 2 sinn θ 1 sin2 θ 2
∑
+ - cos [ nτ ]
Dτ -------------------------------- + sign -------------------------------
sin2 θ 1 sin2 θ 2
0 0 0
sinn θ 1 sinn θ 2
0
τ
(3)
∑ D χ + ∑ --------------------------- r ∑r
Ai Bj + Aj Bi B i B j q i qj
+ o
2 - – 3 ---------- + ---------
6
r 9
nb nb nb
o (4) nb (5) nb (6)
Eq. 11
Angle types The ESFF angle types are classified according to ring, symmetry,
and π-bonding information into five groups:
♦ The normal class includes unconstrained angles as well as those
associated with 3-, 4-, and 5-membered rings. The ring angles
are further classified based on whether one (exo) or both bonds
(endo) are in the ring. Additionally, angles with only central
atoms in a ring are also differentiated.
♦ The linear class includes angles with central atoms having sp
hybridization, as well as angles between two axial ligands in a
metal complex.
Nonbond energy
Partial charges The charges are determined by minimizing the electrostatic energy
with respect to the charges under the constraint that the sum of the
charges is equal to the net charge on the molecule. This is equiva-
lent to equalization of electronegativities.
Derivation The derivation of the rule begins with the following equation for
the electrostatic energy:
∑ ∑
qi q j
E0 + χ q + 1
- η q 2 + Eq. 12
E =
i i i --
2 i i
B ---------
R ij
i i>j
λ – χ i – ∆χ i
q i = ---------------------------- Eq. 13
ηi
( B i ∼ α i2 ⋅ IP ) Eq. 14
a′ b′n eff
α = ------ + ------------- Eq. 15
IP IP
B i ∼ εR 6 Eq. 16
where ε is a well depth, the following forms are deduced for the
rules for van der Waals parameters:
Rules for van der Waals b ⋅ n eff 1/3
a
parameters R i = ------------------ + ------------------ and ε i = c ( IP ) Eq. 17
( IP ) 1 / 3 ( IP ) 1 / 3
The van der Waals parameters are affected by the charge of the
atom.
Modification for metal In ESFF we found it sufficient to modify the ionization potential
atoms (IP) of metal atoms according to their formal charge and hardness:
IP = ( IP ) 0 + qη i Eq. 18
Treatment of nonmetals and for nonmetals to account for the partial charges when calculat-
ing the effective number of electrons.
Atom types The Universal forcefield’s atom types are denoted by an element
name of one or two characters followed by up to three other char-
acters:
♦ The first two characters are the element symbol (for example,
N_ for nitrogen or Ti for titanium).
♦ The third character (if present) represents the hybridization
state or geometry (for example, 1 = linear, 2 = trigonal, R = an
atom involved in resonance, 3 = tetrahedral, 4 = square planar,
5 = trigonal bipyramidal, 6 = octahedral).
♦ The fourth and fifth characters (if present) indicate characteris-
tics such as the oxidation state (for example, Rh6+3 represents
octahedral rhodium in the +3 formal oxidation state; H_ _ _b
indicates a diborane bridging hydrogen type; and O_3_z is a
framework oxygen type suitable for zeolites).
Coverage of the periodic UFF has full coverage of the periodic table. UFF is moderately
table accurate for predicting geometries and conformational energy dif-
ferences of organic molecules, main-group inorganics, and metal
complexes. It is recommended for organometallic systems and
other systems for which other forcefields do not have parameters.
Parameterization The Universal forcefield includes a parameter generator that calcu-
lates forcefield parameters by combining atomic parameters.
Thus, forcefield parameters for any combination of atom types can
be generated as required.
The atomic parameters are combined using a prescribed set of
equations (rules) that generate forcefield parameters for bond,
angle, torsion, inversion (i.e., out-of-plane), and van der Waals and
Coulombic energy terms. For further details, including the gener-
ator equations, see Rappé et al. (1992).
Dummy atoms are used in π-complexation and are associated with
explicit parameters.
Important
To obtain correct results when using UFF, calculate fractional
bond orders after atom typing the structure and before setting
up the energy expression. Cerius2 does this correctly by default,
and you need not worry about it unless you change the default
behavior.
Charges in the Universal The Universal forcefield was developed in conjunction with the
forcefield charge equilibration (Rappé & Goddard 1991) method. Therefore
this method of electrostatic charge calculation is highly recom-
mended for use with the Universal forcefield. For more on the
charge equilibration calculation, see the documentation supplied
with Cerius2•OFF).
Versions UNIVERSAL1.02 is the most up-to-date, and recommended, ver-
sion of the UFF. It includes full bond-order correction. (UFF 1.02
differs from UFF 1.01 in that some explicit torsion parameters were
corrected and one of the oxygen atom-typing rules was modified.)
UFF-VALBOND is UFF with a different function to calculate the
angle energy, so most things which are true for UFF, are true for
UFF-VALBOND.
The burchart1.01–UNIVERSAL1.02 forcefield combines UFF with
the Burchart forcefield. See burchart1.01-UNIVERSAL1.02 for more
information.
VALBOND
Introduction
Most molecular mechanics methods attempt to describe accurate
potential energy surfaces by using a variant of the general valence
forcefield, and a large number of parameters. These simple force-
fields are not accurate outside the proximity of the energetic min-
ima and often are difficult to apply to the different shapes and
higher coordination numbers of transition metal complexes.
In the VALBOND formalism, hybrid orbital strength functions are
used as the basis for a molecular expression of molecular shapes.
These functions are suitable for accurately describing the energet-
ics of distorted bond angles not only around the energy minimum,
but also for very large distortions.
The combination of these functions with simple valence bond
ideas leads to a simple scheme for predicting molecular shapes.
Structures and vibrational frequencies calculated by the VAL-
BOND method agree well with experimental data for a variety of
molecules from the main group of the periodic table.
Validation
Although the original VALBOND was developed for use with the
CHARMM forcefield (Brooks et al., 1983), the table below shows
that the quality of the new UFF-VALBOND forcefield is compara-
ble to the original, and similar to popular forcefields.
Table 4
Ref- Cal-
Molecule Item Calc Ref Diff Exp Exp Exp
Ethane H-C-H 108.7 108.3 0.4 107.5 0.8 1.2
Ethane C-C-H 110.2 110.6 -0.4 111.2 -0.6 -1.0
Propane C-C-C 112.9 112.0 0.9 112.0 0.0 0.9
Propane H-C-H 107.6 107.2 0.4 107.8 -0.6 -0.2
Butane C-C-C 112.9 112.0 0.9 113.3 -1.3 -0.4
Isobutane C-C-C 111.3 110.7 0.6 110.8 -0.1 0.5
Cyclopentane C2-C1-C5 104.4 103.7 0.7 103.0 0.7 1.4
Cyclopentane C1-C2-C3 106.0 104.9 1.1 104.2 0.7 1.8
Cyclopentane C2-C3-C4 106.8 106.4 0.4 105.9 0.5 0.9
Cyclohexane C-C-C 111.9 110.7 1.2 111.4 -0.7 0.5
Cyclohexane H-C-H 107.4 107.7 -0.3 107.5 0.2 -0.1
Methyl-Cyclo- C-C-C(exo) 111.5 110.9 0.6 112.1 -1.2 -0.6
hexane
Norbornane C1-C2-C3 102.5 102.4 0.1 102.7 -0.3 -0.2
Norbornane C2-C1-C6 110.6 109.0 1.6 109.0 0.0 1.6
Norbornane C1-C6-C4 92.7 91.8 0.9 93.4 -1.6 -0.7
Ethylene C=C-H 120.6 120.9 -0.3 121.4 -0.5 -0.8
Propene C=C-C 122.9 122.8 0.1 124.3 -1.5 -1.4
Propene C=C-H 118.6 118.7 -0.1 121.3 -2.6 -2.7
Table 4
Ref- Cal-
Molecule Item Calc Ref Diff Exp Exp Exp
Propene =C-C-H 110.3 110.4 -0.1 116.7 -6.3 -6.4
Cis-2-butene C-C=C 125.3 124.9 0.4 125.4 -0.5 -0.1
Cyclopentene C3-C2=C1 112.0 111.9 0.1 111.0 0.9 1.0
Cyclopentene C2-C3-C4 104.9 104.9 0.0 103.0 1.9 1.9
Cyclopentene C3-C4-C5 106.2 106.3 -0.1 104.0 2.3 2.2
Cyclohexene C-C=C 123.0 123.0 0.0 124.0 -1.0 -1.0
Cyclohexadi- C-C=C 122.8 123.2 -0.4 122.7 0.5 0.1
ene
Cyclohexadi- C-C-C 114.4 113.6 0.8 113.3 0.3 1.1
ene
Norbornene C1-C7-C4 91.8 93.4 -1.6 95.3 -1.9 -3.5
Norbornene C2-C2=C3 106.2 106.7 -0.5 107.7 -1.0 -1.5
Methanol O-C-H(trans) 111.6 112.8 -1.2 107.2 5.6 4.4
Methanol H-C-H 106.3 105.4 0.9 108.5 -3.1 -2.2
1,4-Dioxane C-C-O 112.8 112.5 0.3 109.2 3.3 3.6
1,4-Dioxane C-O-C 114.6 111.7 2.9 112.6 -0.9 2.0
Formaldehyde O-C-H 122.3 122.5 -0.2 121.8 0.7 0.5
Formaldehyde H-C-H 115.4 114.9 0.5 116.5 -1.6 -0.8
Acetaldehyde C-C-H 115.5 115.4 0.1 113.9 1.5 1.6
Acetone C-C-C 117.1 116.0 1.1 116.0 0.0 1.1
Acetone C-C=O 121.4 122.0 -0.6 122.0 0.0 -0.6
Methyl-For- O-C=O 123.8 125.9 -2.1 125.9 0.0 -2.1
mate
Methyl-For- C-O-C 115.0 111.9 3.1 114.8 -2.9 0.2
mate
Acetic Acid O-C=O 116.8 117.6 -0.8 126.6 -9.0 -9.8
Acetic Acid O-C-O 117.3 117.5 -0.2 110.6 6.9 6.7
Acetic Acid O-C=O 126.0 124.6 1.4 123.0 1.6 3.0
Methyl Ace- C-O-C 116.1 115.1 1.0 114.8 0.3 1.3
tate
Piperazine C-C-N 110.9 110.8 0.1 109.8 1.0 1.1
Piperazine C-N-C 115.6 113.8 1.8 112.6 1.2 3.0
Nitromethane [N-C-H] 110.2 109.8 0.4 107.2 2.6 3.0
Table 4
Ref- Cal-
Molecule Item Calc Ref Diff Exp Exp Exp
Succinamide N-C=O 119.6 121.4 -1.8 122.0 -0.6 -2.4
Succinamide C-C-N 116.9 114.0 2.9 116.0 -2.0 0.9
Succinamide C-C=O 123.6 124.5 -0.9 122.0 2.5 1.6
Acetamide C-C-N 117.6 117.5 0.1 115.1 2.4 2.5
BHF2 F-B-F 118.4 118.1 0.3 118.3 -0.2 0.1
BHCl2 Cl-B-Cl 121.1 119.6 1.5 119.7 -0.1 1.4
BF2NH2 F-B-F 119.6 119.9 -0.3 117.9 2.0 1.7
BF2NH2 H-N-H 114.4 115.0 -0.6 116.9 -1.9 -2.5
NH3 H-N-H 106.8 106.8 0.0 106.7 0.1 0.1
NCl3 Cl-N-Cl 106.5 106.5 0.0 107.1 -0.6 -0.6
NHCl2 H-N-Cl 106.8 106.7 0.1 102.0 4.7 4.8
NHCl2 Cl-N-Cl 106.1 106.1 0.0 106.0 0.1 0.1
NH2Cl H-N-H 107.1 107.1 0.0 106.8 0.3 0.3
NH2Cl H-N-Cl 106.4 106.3 0.1 102.0 4.3 4.4
N3- N-N-N 179.9 180.0 -0.1 180.0 0.0 -0.1
NClO Cl-N-O 114.6 114.2 0.4 113.3 0.9 1.3
PH3 H-P-H 93.8 93.8 0.0 93.3 0.5 0.5
PCl3 Cl-P-Cl 100.1 100.1 0.0 100.1 0.0 0.0
CH3PH2 C-P-H 93.1 97.1 -4.0 96.5 0.6 -3.4
CH3PH2 H-P-H 91.3 91.3 0.0 93.4 -2.1 -2.1
(CH3)2PH C-P-C 99.7 98.5 1.2 99.7 -1.2 0.0
(CH3)2PH C-P-H 91.2 95.6 -4.4 97.0 -1.4 -5.8
(CH3)3P C-P-C 97.0 95.6 1.4 98.6 -3.0 -1.6
AsH3 H-As-H 91.7 91.7 0.0 92.1 -0.4 -0.4
AsF3 F-As-F 96.0 96.0 0.0 96.0 0.0 0.0
AsCl3 Cl-As-Cl 98.7 98.7 0.0 98.6 0.1 0.1
AsBr3 Br-As-Br 99.6 99.6 0.0 99.7 -0.1 -0.1
AsI3 I-As-I 100.2 100.2 0.0 100.2 0.0 0.0
O3 O-O-O 116.8 116.8 0.0 116.8 0.0 0.0
(CH3)2O C-O-C 114.7 111.6 3.1 111.7 -0.1 3.0
(CH3)2S C-S-C 100.1 99.3 0.8 98.9 0.4 1.2
(CH3)2Se C-Se-C 96.9 96.2 0.7 96.0 0.2 0.9
Table 4
Ref- Cal-
Molecule Item Calc Ref Diff Exp Exp Exp
(SiH3)2O Si-O-Si 142.6 142.7 -0.1 144.1 -1.4 -1.5
(SiH3)2S Si-S-Si 99.4 99.6 -0.2 97.4 2.2 2.0
(SiH3)2Se Si-Se-Si 97.9 98.0 -0.1 96.6 1.4 1.3
(GeH3)2O Ge-O-Ge 126.1 126.2 -0.1 126.5 -0.3 -0.4
(GeH3)2Se Ge-Se-Ge 93.9 94.1 -0.2 94.6 -0.5 -0.7
Si4O4C8H24 Si-O-Si 143.4 143.4 0.0 142.5 0.9 0.9
Si4O4C8H24 O-Si-O 112.1 112.4 -0.3 109.0 3.4 3.1
Si4O4C8H24 C-Si-C 107.4 107.3 0.1 106.0 1.3 1.4
Ge4S6(CF3)4 [S-Ge-S] 114.6 113.8 0.8 113.8 0.0 0.8
Ge4S6(CF3)4 [Ge-S-Ge] 97.9 99.9 -2.0 99.9 0.0 -2.0
Sn6Ph12 [Sn-Sn-Sn] 112.8 112.4 0.4 112.5 -0.1 0.3
Sn6Ph12 C-Sn-C 107.0 105.5 1.5 106.7 -1.2 0.3
B3Ph3O3 [B-O-B] 121.8 121.8 0.0 121.7 0.1 0.1
B3Ph3O3 [O-B-O] 118.2 118.2 0.0 118.0 0.2 0.2
PO4P3O3 O1-P1-O2 114.1 114.1 0.0 115.0 -0.9 -0.9
PO4P3O3 O2-P1-O4 104.5 104.5 0.0 103.0 1.5 1.5
PO4P3O3 O2-P2-O3 99.4 99.3 0.1 99.0 0.3 0.4
PO4P3O3 P2-O2-P1 121.7 122.9 -1.2 124.0 -1.1 -2.3
PO4P3O3 P2-O3-P3 128.8 127.3 1.5 128.0 -0.7 0.8
Ga2Pyr2Br4 Br-Ga-Br 107.2 107.0 0.2 105.8 1.2 1.4
Ga2Pyr2Br4 Ga-Ga-Br 114.3 115.1 -0.8 116.3 -1.2 -2.0
As3(CH3)6In6(C C-In-C 101.7 101.9 -0.2 99.0 2.9 2.7
H3)6
As3(CH3)6In6(C C-As-C 125.6 124.7 0.9 126.0 -1.3 -0.4
H3)6
Applicability
UFF-VALBOND can be used for compounds containing elements
from across the periodic table.
5. Select atoms from the model window and set the appropriate
VALBOND centers.
Note
It is possible to assign VALBOND centers with any forcefield
loaded. However for the angle energy function to be used, the
forcefield must be specifically defined to use the VALBOND
bend energy function. Currently only the UFF_VALBOND1.01
uses this function.
Bond Hybridization
Bond hybridization is the net hybridization of an individual bond
connected to a VALBOND center. The hybridization is a function
of the nature of the VALBOND center, its gross hybridization, and
the number and nature of all the ligands connected to the VAL-
BOND center.
For example the gross hybridization of the N atom in ammonia,
NH3, equals three (sp3).
The bond hybridization of the N-H bonds is calculated as sp3.47.
The gross hybridization of O in water is three, and the bond
hybridization of the O-H bond is sp3.87. Thus VALBOND calcu-
lates these bonds to have more p character than the C-H bond in
say methane, where both gross and bond hybridizations are sp3,
exactly.
Bond hybridizations are calculated when VALBOND centers are
assigned.
Examples
Standard Minimization ♦ From OFF Setup load UFF_VALBOND1.01 via the Open Force
Field card.
♦ From OFF Methods select Minimizer and Run.
Minimization of hyperval- ♦ From OFF Setup load UFF_VALBOND1.01 via the Open Force
ent compound Field card.
♦ From the Open Force Field card select Energy Expression -
Automate Setup.
♦ Disable the Perform Valbond Initialization option.
♦ From the Open Force Field card select Typing - VALBOND
centers.
♦ Select the appropriate atoms from the model window and set as
VALBOND centers
OR
set all atoms as VALBOND centers and unset selected atoms.
♦ From OFF Methods select Minimizer and Run.
Dreiding forcefield
General force constants and geometry parameters for the Dreiding
forcefield are based on simple hybridization rules rather than on
Classical forcefields
Availability Classical forcefields provided by MSI include AMBER,
CHARMm, and CVFF:
♦ The standard AMBER forcefield (Standard AMBER forcefield)
has been supplemented (Homans’ carbohydrate forcefield), so as to
cover oligosaccharides. This enhanced AMBER forcefield is the
version that is run via the Discover program, as available in the
Insight•Discover and Insight•Discover_3 modules. (Nonvali-
dated versions of AMBER are also available for the
Cerius2•Open Force Field module, in the directory named
“untested”, see untested directory.)
♦ The CHARMm forcefield (CHARMm forcefield) is run through
the CHARMm program as implemented in the QUANTA
molecular modeling interface.
♦ The CVFF forcefield (CVFF, consistent valence forcefield) is run
via the Discover program, as available in the Insight•Discover,
Insight•Discover_3, and Cerius2•Discover modules, and via
the Cerius2•Open Force Field module.
Characteristics The parameters of classical forcefields were derived by fitting
experimental data sets. They were generally designed for biologi-
cal macromolecules, although they have been used or adapted for
other classes of models. Since they are relatively old, they are well
characterized and many research studies have used them.
AMBER forcefield
The standard AMBER forcefield (Weiner et al. 1984, 1986) is
parameterized to small organic constituents of proteins and
nucleic acids. Only experimental data were used in parameteriza-
tion.
However, AMBER has been widely used not only for proteins and
DNA, but also for many other classes of models, such as polymers
and small molecules. For the latter classes of models, various
authors have added parameters and extended AMBER in other
ways to suit their calculations. The AMBER forcefield has also
∑ K ( b – b ) + ∑ H (θ – θ ) + ∑ -----2- [ 1 + cos ( nφ – φ ) ]
2 2 Vn
E pot = 2 0 θ 0 0
b (1) θ (2) φ (3)
∑ ε[ ( r*/r) ∑ q q /ε r + ∑
C ij D ij
+ 12 – 2 ( r*/r ) 6 ] + i j ij ij ------- – -------
r ij12 r ij10
(4) (5) (6)
Eq. 19
CHARMm forcefield
CHARMm, which derives from CHARMM (Chemistry at HAR-
vard Macromolecular Mechanics), is a highly flexible molecular
mechanics and dynamics program originally developed in the lab-
oratory of Dr. Martin Karplus at Harvard University. It was
parameterized on the basis of ab initio energies and geometries of
small organic models.
Applicability CHARMm performs well over a broad range of calculations and
simulations, including calculation of geometries, interaction and
conformation energies, local minima, barriers to rotation, time-
dependent dynamic behavior, free energy, and vibrational fre-
quencies (Momany & Rone, 1992). CHARMm is designed to
give good (but not necessarily “the best”) results for a wide
variety of modelled systems, from isolated small molecules to
solvated complexes of large biological macromolecules; however,
it is not applicable to organometallic complexes.
Functional form CHARMm uses a flexible and comprehensive empirical energy
function that is a summation of many individual energy terms.
The energy function is based on separable internal coordinate
terms and pairwise nonbond interaction terms (Brooks et al. 1983).
The total energy is expressed by the following equation:
E pot =
∑ k (r – r ) + ∑ K (θ – θ ) + ∑ k
b 0
2
θ 0
2
φ – k φ cos ( nφ ) +
∑ k (χ – χ )
χ 0
2 Eq. 21
A ij B ij
∑ ∑
qi qj
+ ------------------ + - – ------ sw ( r ij2 , r on
------ 2 , r2 ) + E
off constraint + E user
4πε 0 r if r 12 r 6
A B
E = --------- – ------ cosm ( φ A – H – D ) cosn ( φ AA – A – H )
r 6AD r 4A
2 2 2
: switch(r AD, r on, r off)
eters are present. These are noted in the output file from the calcu-
lation.
Applicability CVFF was fit to small organic (amides, carboxylic acids, etc.) crys-
tals and gas phase structures. It handles peptides, proteins, and a
wide range of organic systems. As the default forcefield in Dis-
cover, it has been used extensively for many years. It is primarily
intended for studies of structures and binding energies, although
it predicts vibrational frequencies and conformational energies
reasonably well.
Out-of-planes and the The CDiscover program has undergone extensive validation tests
two versions of Discover comparing it with FDiscover. These tests have indicated that the
two programs provide exactly the same results for all components
of the energy expression with one exception: the out-of-plane
energy for the CVFF forcefield.
The out-of-plane energy for the CVFF forcefield is calculated as an
improper torsion. An improper torsion views three connected
atoms and a central atom as if it were a torsion (see Table 24). There
are three possible improper torsions that can be generated for a
particular out-of-plane, based on permutations of the connected
atoms.
For CVFF, only one of these improper torsions is used. The rules
that FDiscover employs to select the particular improper torsion
are somewhat arbitrary, and it was not possible to replicate them
in CDiscover. However, the changes in energy are very small (on
the order of 0.01 kcal mol-1). (A more rigorously defined out-of-
plane, the Wilson out-of-plane, is used in the CFF forcefield. This
energy term provides exact agreement between CDiscover and
FDiscover.)
Functional form
The analytic form of the energy expression used in CVFF is shown
in Eq. 23.
∑ D [1 – e ∑ H ( θ – θ ) + ∑ H [ 1 + s cos (nφ) ]
–α ( b – b0 )
E pot = b ]+ θ 0
2
φ
+
∑H χ + ∑∑F
χ
2
bb′ ( b – b 0 ) ( b′ – b′0 ) +
∑∑F θθ′ ( θ – θ 0 ) ( θ′ – θ′0 )
+
∑∑F bθ ( b – b0 ) ( θ – θ0 ) +
∑F φθθ′ cos φ ( θ – θ 0 ) ( θ′ – θ′0 ) +
∑∑F χχ′ χχ′
+
∑ ε[ ( r*/r) 12 – 2 ( r*/r ) 6 ] +
∑ q q /εr i i ij
(10) (11)
Eq. 23
Types of terms and com- Terms 1–4 are commonly referred to as the diagonal terms of the
putational costs valence forcefield and represent the energy of deformation of bond
lengths, bond angles, torsion angles, and out-of-plane interactions,
respectively.
A Morse potential (Term 1) is used for the bond-stretching term.
The Discover program also supports a simple harmonic potential
for this term. The Morse form is computationally more expensive
than the harmonic form. Since the number of bond interactions is
usually negligible relative to the number of nonbond interactions,
the additional cost of using the more accurate Morse potential is
insignificant, so this is the default option.
When not to use the When the model being simulated is high in energy (caused, for
Morse term example, by overlapping atoms or a high target temperature), a
Morse-style function might allow bonded atoms to drift unrealis-
tically far apart (see Figure 2). This would not be desirable unless
you were intending to study bond breakage.
Use of crossterms Terms 5–9 are off-diagonal (or cross) terms and represent cou-
plings between deformations of internal coordinates. For example,
Term 5 describes the coupling between stretching of adjacent
bonds.
A B
Special-purpose forcefields
Availability Several forcefields are provided by MSI that are specialized for
certain uses:
♦ Forcefields optimized for glasses (Glass forcefield), for polyvi-
nylidene fluoride (MSXX forcefield for polyvinylidene fluoride),
and for zeolites (Zeolite forcefields), as well as forcefields
intended for use only in the Cerius2•Morphology module
(Forcefields for Cerius2•Morphology module), are accessed through
the Cerius2•Open Force Field module.
♦ The PCFF (PCFF forcefield for polymers and other materials), COM-
PASS (COMPASS forcefield for organic and inorganic materials),
and augmented CVFF (Augmented CVFF) forcefields, which are
run via both Cerius2•OFF and the Discover program, are ver-
sions of standard forcefields that have been extended for use
with polymers and zeolites, respectively.
Characteristics The specialized forcefields described in the following sections
have been developed for the purpose of simulating certain sys-
Glass forcefield
The Glass forcefield (Glassff) exists in versions that include two-
and three-body nonbond terms (glassff_1.01 and glassff_2.01,
respectively) and is used for studying a range of inorganic oxide
glasses (and other ionic systems) under periodic boundary condi-
tions. The newer, three-body, glass forcefield is recommended and
documented here.
The glass forcefield is applicable to systems containing Si, O, Al,
Li, Na, K, Mg, Ca, B, and Ti. Predicted properties include structure,
radial distribution functions, angular distributions, and short-
range order.
The form of interaction and parameterization for this forcefield is
based mainly on the work of Soules, Garofalini, and co-workers
(Soules 1979, Soules & Varshneya 1981, Garofalini 1984, Tesar &
Varshneya 1987, Rosenthal & Garofalini 1987, 1988, Zirl & Garo-
falini 1989, Garofalini & Zirl 1990, Kohler & Garofalini 1994).
Functional form All ion pairs are subjected to an interaction containing a repulsive
van der Waals term and a screened Coulombic term.
The screeening of the Coulombic potential with the complemen-
tary error function represents an approximate Ewald summation
in real-space only (Woodcock 1975). The reciprocal-space Ewald
sum is omitted, to be able to model a bulk amorphous system with
finite computational resources. This also reduces the effects of the
imposed periodicity of the simulation model.
The potential equation is:
q i qj
V ij ( r ) = A ij exp ( – r ij ⁄ p ) + C --------- erfc ( r ij ⁄ βij ) Eq. 24
εr ij
Where:
Aij A pre-exponential constant specific to each element-pair
van der Waals interaction.
qi qj ri + r j
A ij = 1 + ---- + ---- b exp -------------- Eq. 25
n i n j ρ
Where:
qi Formal charge on ion i.
ni Number of valence-shell electrons in ion i.
b 3.38E-20 J.
ri Radius repulsion constant of the element ion i, related to
the ionic radius.
ρ 0.29 Å.
For the glass forcefield, A parameters were computed for the full
set of ion-pair interactions using quoted values of r. Where explicit
values of Aij existed in the literature, these were preferred. This
produced a parameter set able to tackle a range of ions:
O2-, Si4+, Al3+, Li+, Na+, K+, Mg2+, Ca2+, Zn2+, Ti4+, B3+
Automated setup For models within the scope of the glass forcefield, the default
Open Force Field settings included in the file can be used without
adjustment. Atom typing and charging also can be done automat-
ically.
Note
The MSXX forcefield uses the Morse functional form for bond
stretching, which means that the force goes to zero at large bond
distances (see Figure 2). Therefore this forcefield should not be
used when starting a run with bad initial geometries. Instead,
use an alternative forcefield (e.g., the Universal forcefield)
when starting from a bad geometry and then switch to the
MSXX when close to the energy minimum.
Zeolite forcefields
See also documentation on the augmented CVFF (Augmented
CVFF).
bks1.01 The BKS forcefield was developed by van Beest et al. (1990) to
describe the geometries, vibrational frequencies, and mechanical
properties of silicas and aluminophosphates. The parametrization
is based on both ab initio and experimental data. The forcefield
contains four atom types: Si, O, Al, and P.
Interatomic interactions are considered to be ionic (nonbond)
rather than covalent. The van der Waals interactions are described
with a Buckingham potential, and the electrostatic interactions are
described by atomic monopoles and a Coulombic term.
burchart1.01 The Burchart forcefield was developed by Burchart (1992) to
describe the geometry, heats of formation, transitions under pres-
sure, crystal morphology, and vibrational frequencies of silicas
and aluminophosphates. The parametrization is based mainly on
experimental data and includes both valence and nonbond terms.
It contains four atoms types: Si, O, Al, P.
This forcefield treats the zeolite framework as largely covalent.
Bond-stretching is described by the Morse term, 1–3 interactions
by the Urey–Bradley term, van der Waals interactions by an expo-
nential-6 term, and electrostatic interactions by partial atomic
charges and a screened Coulombic term.
The Cerius2 implementation of the Burchart forcefield differs from
the published version in three respects:
♦ The Cerius2 implementation of the forcefield ignores the Cou-
lombic interaction if the atom pair interacts via a bond interac-
tion, but Burchart allows both bond and Coulombic
interactions for a pair of atoms.
♦ The Cerius2 implementation of the forcefield does not allow
Coulombic or van der Waals interactions between two atoms
Note
When using the GRAFDREIDING1.00 forcefield, if you load in
a Biodesign (bgf) format structure file that already has the
correct atom types assigned (for example, a structure that was
atom typed using the default Dreiding forcefield rules and
saved in a POLYGRAF Biodesign file with its default atom
types), do not atom type the structure again.
untested directory The untested directory contains several forcefields that have not
been validated by Molecular Simulations. Some are incomplete
and intended only as examples of how to incorporate parameters
from other forcefields. We supply these forcefields as a conve-
nience to our customers, but do not support them.
♦ amber1.01 — This forcefield file is based on the AMBER
(Weiner et al. 1984, 1986) forcefield developed for the simula-
tion of proteins and nucleic acids. Its atom types are limited to
those needed for these structures: H, C, O, S, N, and P.
♦ amber2.01 — This forcefield is an extension of the amber1.01
forcefield. In addition to the atom types of amber1.01, it con-
tains atom types for several biologically important cations: Br,
Na, Cl, and Ca.
♦ mm2_77_1.01 and mm2_85_1.01 — These forcefields are based
on the MM2 and MMP2 forcefields developed by Allinger’s
group (Kao & Allinger 1977, Liljefors et al. 1987, Sprague et al.
1987). They are particularly suitable for small organic models.
The mm2_77 forcefield applies only to saturated hydrocarbons,
and the mm2_85 forcefield is a significant extension of the MM2
and MMP1 forcefields. The mm2_85 parameters are compatible
with those of mm2_77, but calculations on conjugated systems
can be done with the mm2_85 forcefield. The mm2_85 force-
field also has more atom types for a much larger range of ele-
ments.
♦ The “CFF93” forcefield for hydrocarbons (cff93_1.01), although
not in the untested directory, is no longer supported, since it has
been superceded by the CFF91 and CFF forcefields, which
should be used instead.
Related information in this Forcefields presents the functional forms of energy expressions and
book describes the forcefields that are available in Molecular Simula-
tions products.
The atom types defined for each forcefield are listed under Force-
field Terms and Atom Types.
The files that specify the forcefields are described in detail in sep-
arate documentation.
Table 5. Finding information in Preparing the Energy Expression and the Model section
Table 5. Finding information in Preparing the Energy Expression and the Model section
Specific information For specific information on procedures, please see the manual for
the molecular modeling program and/or simulation engine that
you are using (see Available documentation):
Using forcefields
Graphic interface mode All MSI’s simulation engines and forcefields can be used through
at least one graphical molecular modeling interface (Cerius2,
Insight II, QUANTA, see Table 1).
Standalone mode The Discover and CHARMm programs can also be run in a com-
mand-based, standalone mode with input from a text interface
and/or a script and other input files.
Mixed-mode use For Discover and CHARMm, you can optionally perform some
tasks through the appropriate graphical interface and others in
standalone mode. For example, you might want to prepare model
structure and command input files with the graphical interface,
save both types of files, edit the command input file with a text edi-
tor so as to perform some complex simulation, start the run in stan-
dalone mode, and then analyze the results with the aid of one of
the graphical interfaces. In addition, facilities exist for directly
entering specific BTCL or CHARMm commands from the Insight
or QUANTA interface and for reading a BTCL or CHARMm com-
mand input file into the Insight, Cerius2, or QUANTA interface.
Additional information How to run Discover and CHARMm in standalone mode is docu-
mented separately (see Available documentation).
General procedure Regardless of whether simulation engines are run through the
graphical interface, in standalone mode, or in some combination of
both modes, the general sequence of activities for doing forcefield-
based calculations is as follows.
Important
For specific instructions, see the documentation for the
appropriate simulation engine and/or molecular modeling
program (see Available documentation).
Selecting forcefields
For details on how to select a forcefield in the molecular modeling
program that you are using, please see the appropriate specific
documentation (see Available documentation). A brief summary:
♦ Cerius2•Discover—Use the Run Discover control panel (which
is accessed by selecting Run on the DISCOVER menu card) or
the Select Discover Forcefield control panel (accessed by select-
ing Forcefield/Select on the DISCOVER card).
♦ Cerius2•OFF—Use the Load Force Field control panel, which
is accessed by selecting Load on the OPEN FORCE FIELD
menu card.
♦ Cerius2•MMFF, go to the MMFF card deck and select Run to
access the MMFF Energy Minimization control panel (check the
Use MMFF For Energetic Calculations check box if you want
MMFF93 to be used for calculations in other relevant modules).
♦ Insight II—Use the Forcefield/Select parameter block. This
parameter block is found in several modules, including the
Builder.
♦ QUANTA—Use the CHARMm/CHARMm Mode menu item
on the main QUANTA menu bar.
Important
A newly assigned atom type (including associated parameters
such as mass and charge) replaces any previously assigned or
calculated value.
Important
Currently, the automatic atom-typing engines cannot
distinguish a metal atom from a metallic ion. Hence, by default,
“metal” atom types are assigned by the automatic typing
engines. So for metal ions, you need to assign the formal charges
and atom types by hand.
Assigning charges
Charges (when available) are generally assigned at the same time
as the forcefield atom type (see Assigning atom types to a model).
An atom-type charge is simply a fixed value associated with the
atom types. Overall neutrality of a model is not necessarily
achieved by assigning forcefield atom types. You may prefer to
assign charges specifically. (The exact method depends on the
molecular modeling program being used.)
Importance of correct Electrostatic interactions play a critical role in determining the
charge assignment structures of inorganic systems and in defining the packing of
organic molecules.
Many forcefields already Forcefields that include Coulombic terms generally already
include charges include standard charges (or “bond increments”) associated with
the atom types. These forcefields have been parameterized with
nonzero atom type charges or charge increments (Table 6) and
therefore you usually just assign charges automatically when you
do atom typing, instead of having to assign specific charges:
Forcefield Engine
CFF91–95, CFF, PCFF, COMPASS OFF, Dis-
cover
CVFF OFF, Dis-
cover
bks1.01 OFF
burchart1.01 OFF
burchart1.01-DREIDING2.21 (not all atom types) OFF
burchart1.01-UNIVERSAL1.02 (Burchart atom types only) OFF
glassff_1.01 OFF
MMFF93 CHARMma
msxx_1.01 OFF
CHARMm CHARMm
a
CHARMm as run through the Cerius2•MMFF module, not in QUANTA or stan-
dard CHARMm.
Important
If you want to assign charges different from those in the
forcefield, you need to assign the charges after atoms typing
(and automatic charge assignment) is done.
Finding charges, if If you need to specifically assign charges, most relevant modules
needed allow you to set atomic charges directly or specify an overall net
charge for the whole structure using charge editing functions.
For small models, you can obtain values for charges by using an ab
initio or semiempirical quantum chemistry module (for example,
MOPAC).
For larger, distorted, models and when charge assignment is done
by the charge equilibration method (in Cerius2), you usually need
Parameter assignment
Who should read this sec- If you are a novice user or routinely run relatively simple calcula-
tion tions on relatively simple or standard models, you do not need to
read this section. However, if, for example, an error message
informs you of missing parameters or you want to customize your
energy expression for an atypical model, then you do need to
understand how the simulation engines determine what parame-
ters are used for which atoms, bonds, angles, etc.
You should also understand something about atom type and
charge assignment (Assigning forcefield atom types and charges) to
make effective use of this section.
Automatic
Modeling program parameters Comments
What happens if parame- Some classic and second-generation forcefields are not completely
ters are not found parameterized for all their atom types. (For rules-based forcefields
(Rule-based forcefields broadly applicable to the periodic table), all
parameters are generated according to rules rather than read from
the forcefield file.) When parameters for classic and second-gener-
ation forcefields are not available, one of several things can hap-
pen, with varying consequences:
♦ The missing parameters are simply ignored (i.e., set to zero in
the energy expression). The simulation runs and yields results,
but they may be very inaccurate.
♦ Setup of the energy expression is interrupted, the simulation
run is not started, and a message is output to the textport or text
window.
♦ Missing parameters are obtained automatically from a simpler
generic set of parameters (using many wildcards, see above).
The results may be reasonable, but not as accurate as if specific
parameters existed.
Temporary patches for A forcefield may include automatic parameters for use when bet-
missing parameters; pre- ter-quality explicit parameters are not defined for a particular
cautions bond, angle, torsion, or out-of-plane interaction. These parameters
are intended as temporary patches, to allow you to begin calcula-
tions immediately. While MSI has made every effort to ensure that
the automatic parameters used in CVFF, the CFF family of force-
fields, and CHARMm produce reasonable geometries for a wide
An example As an example, the parameters for the angle oh–c"–c" in oxalic acid
(Figure 3) are not present in CFF91.
h*
oh o’
c" c" h*
o’ oh
Figure 3. Oxalic acid structure and CFF91 atom types
! Equivalences
! -----------------------------------------------------------------------------
!Ver Ref Type NonB Bond Bond Angle Angle Torsion Torsion OOP OOP
Inct End Atom Apex Atom End Atoms Center Atoms End Atom Center Atom
!--- --- ---- ---- ---- --- -------- ----------- --------- ------------ -------- -----------
2.0 2 c" c" c" c’_ c_ c’_ c_ c’_ c_ c’_
2.0 2 oh o o_ o_ o_ o_ o_ o_ o_ o_
…
#quadratic_angle cff91_auto
Editing a forcefield
Expert users can edit MSI forcefields in different ways to custom-
ize them to their needs or to create new forcefields.
Editing through a graphi- MSI’s principal molecular modeling programs include forcefield
cal interface editors (see Available documentation):
♦ Cerius2 —Use the Force Field Editor (in the OFF SETUP card
deck), which allows you to edit all existing defined terms in the
current forcefield and also lets you create new forcefields. The
Cerius2•FFE module also allows you to create, edit, and delete
atom types and to change the rules on which automatic atom-
typing is based.
You can change the functional form of terms in rules-based
forcefields (see Rule-based forcefields broadly applicable to the peri-
odic table) by adding an explicit term. Any explicit term is
always used in preference to a generated term.
Important
The Cerius2•FFE module cannot be used to modify the CFF or
CVFF forcefield files that are included with Cerius2 —if you
want to use customized versions of these forcefields, you need
to modify them with Insight II 4.0.0 or as described in the
Discover documentation.
Important
For forcefields accessed through Cerius2, we strongly
recommend that you never edit these files by hand. Please use
the Force Field Editor module. This is important because some
forcefield values are linked to others and only the Force Field
Editor reliably assures that related values are modified in a
coordinated way.
♦ With the CVFF forcefield in Discover, you can choose to turn off
(i.e., not use) all cross terms.
♦ You can accomplish the same end for other terms in CVFF and
for any class of terms in the other forcefields supplied with the
Discover program by scaling terms with a zero scaling factor
(see next section).
♦ In CHARMm, you can omit (“skip”) any type(s) of terms or
constraints, for example, all bond terms.
Inversion terms
The inversion, improper, or out-of-plane torsion term represents
the energy involved in inverting a chiral center or otherwise
changing this out-of-plane angle.
In Cerius2•OFF, you may use the first inversion term found or the
average of all inversion energies, but the first approach is not rec-
ommended.
k [ ( sr min ) 2 – r 2 ] 2 Eq. 26
The quartic form is useful when you need to eliminate bad van der
Waals contacts, but the second derivatives are not calculated.
Lack of hydrogen bond If specific hydrogen bonds are required, generation of a list of
terms is an asset hydrogen bonds is a major step in evaluating the energy of a sys-
tem. This process involves looking at all possible pairs of hydro-
gen bond donors and acceptors and selecting those that meet
certain criteria (Figure 5):
♦ The hydrogen bond length is less than a defined cutoff.
♦ The deviation of D–H–A from linearity is less than a defined
cutoff. Typically, the best hydrogen bond has a D–H–A angle of
180°.
angle
A
H
D
ce
distan
Figure 5. Distance and angle criteria for hydrogen bonds
A = hydrogen acceptor; D = hydrogen donor.
In CHARMm, you can change the hydrogen bond criteria with the
CHARMm Update Parameters dialog box, which is accessed from
the CHARMm/Update Parameters menu item. This dialog box
also allows specification of switching function parameters for
hydrogen bonds. Setting the Update Frequency to 0 (the default)
effectively omits the hydrogen bond term from the potential
energy expression. You can also omit explicit hydrogen bond
terms by using the CHARMm/Energy Terms menu item.
Availability
constraint/re-
straint type enginea details
b
atom fixed (constraints) OFF , FDiscover, CDis- here
cover, CHARMm
template forc- harmonic (Eq. 28) restraint FDiscover here
ing
tethering and quadratic (Eq. 29) restraint CDiscoverc here
template
forcing
tethering harmonic (Eq. 28) restraint FDiscover here
tethering mass-weighted harmonic (Eq. 30) restraint CHARMm here
quartic droplet harmonic (Eq. 31) restraint CHARMm here
distance harmonic (Eq. 32) restraint OFF here
distance quadratic (Eq. 29), flat-bottomed (Eq. 34), CDiscover3 here
or cosine (Eq. 36) restraint
distance harmonic (Eq. 32) or flat-bottomed (Eq. 33) FDiscover here
restraint
distance flat-bottomed (Eq. 35) restraint CHARMm here
dynamics RATTLE algorithm (constraints) CDiscover here
dynamics SHAKE algorithm (constraints) CHARMm here
dynamics consensus dynamics (Eq. 28) (standalone FDiscover, CDiscover here
only)
angle harmonic (Eq. 37) restraint OFF here
angle quadratic (Eq. 29), flat-bottomed (Eq. 34), CDiscoverc here
or cosine (Eq. 36) restraint
torsion harmonic (Eq. 38) restraint OFF here
torsion quadratic (Eq. 29), flat-bottomed or J3 dihe- CDiscoverc here
dral (Eq. 34), cosine (Eq. 36), cis (Eq. 39),
trans (Eq. 40), or cis/trans (Eq. 41) restraint
torsion flat-bottomed (Eq. 33) restraint (standalone FDiscover here
only)
torsion cosine (Eq. 42) or harmonic (Eq. 38) torque FDiscover here
(one of these is standalone only)
torsion harmonic (Eq. 38) restraint CHARMm here
inversion harmonic (Eq. 43) restraint OFF here
constraint/re-
straint type enginea details
3
chiral flat-bottomed (Eq. 34) restraint CDiscover here
out-of-plane quadratic (Eq. 29), flat-bottomed or J3 dihe- CDiscover3 here
dral (Eq. 34), or cosine (Eq. 36) restraint
out-of-plane harmonic (Eq. 43) restraint (standalone FDiscover here
only)
aThe standalone modes of running simulation engines may give access to additional constraints and
restraints—please see the appropriate documentation.
b
The Open Force Field module in Cerius2.
c
Not available yet in the Cerius2•Discover module; restraints applied with CDiscover (in Insight and stan-
dalone modes) can also be scaled.
Important
The energy calculated by simulation engines is correct only to
an arbitrary constant, depending on the model as well as the
fixed atoms. Thus, only differences in energy between
conformations of the same model having the same fixed atoms
are meaningful.
1/2
N 2
R – R template
i
∑
i
E = K --------------------------------------- Eq. 27
N
pairs
or:
N
2
E =
∑ K i R – R template
i i
Eq. 28
pairs
0 r < r min
K i = k min + k max – k min × ( r – r min ) ⁄ ( r msx – r min ) r min ≤ r ≤ r max
k max r max < r
where rmin is the distance at which the tethering turns on, kmin is
the initial force constant at that distance, rmax is the distance where
the force constant reaches its maximum allowed value, and kmax is
the maximum allowed force constant. If rmin and kmin are not
given, the default values are zero. If rmax is zero, tethering uses a
constant force constant of kmax.
In CDiscover, a simpler quadratic is used:
E cons =
∑ k m (r – r )
i i i 0
n Eq. 30
E droplet = k
∑ m (r – r i i COM )
n Eq. 31
E = K ( R ij – R target ) 2 Eq. 32
E + ( R – R )F R ij < R 1
1 1 ij
K 2 ( R ij – R 2 ) 2 R 1 < R ij ≤ R 2
E = 0 R 2 < R ij ≤ R 3 Eq. 33
K ( R – R )2 R 3 < R ij ≤ R 4
3 ij 3
E + ( R – R )F R 4 < R ij
4 ij 4
k ( V – V0 )
2 V ≤ V0
E = scale factor 0.0 V0 < V < V1 Eq. 34
k ( V – V1 )
2 V ≥ V1
k min
---------- ( R – R min ) 2 R < R min
2
0 R min < R < R max
E = k min Eq. 35
---------- ( R – R max ) 2 R max < R < R lim
2
R lim + R max
f R – ---------------------------- R <R
max 2 lim
0
R1 R2 R3 R4
E(r)
0
R1 R2 R3 R4
0
R1 R2 = R3 R4
k
E = scale factor --- ( 1 – cos ( n ( V – V 0 ) ) ) Eq. 36
2
Angle restraints
In Cerius2, an angle restraint can be applied to a group of any three
atoms. The restraint is implemented such that:
E = 0.5K a ( θ – θ 0 ) 2 Eq. 37
Torsion restraints
Uses Some uses of torsion restraints are to enforce chiral and prochiral
centers, prevent cis–trans conversions, and fit NOE J-coupling con-
stants from NMR experiments. Conversely, other uses are to force
torsion rotation in order to perform phi/psi mapping, perform
conformational searching, and induce conformational changes.
Functional forms Several forms of torsion restraints are used in the literature and
implemented in MSI’s simulation engines.
Harmonic restraints, or periodic restraints (Eq. 42 with n = 1), are
appropriate for forcing a torsion angle to a particular value. The
periodic form with a periodicity greater than one is useful for
restraining a torsion to one of several related angles. For instance,
a threefold potential could keep a torsion either trans or at one of
the two gauche conformations, depending on the starting confor-
mation and the strength of the potential applied.
Implementation In Cerius2•OFF, a torsion (dihedral) restraint can be defined
among any group of four atoms. The restraint is implemented such
that:
E = K t ( φ – φ0 )2 Eq. 38
k
E = scale factor --- ( 1 – cos φ ) Eq. 39
2
or trans:
k
E = scale factor --- ( 1 + cos φ ) Eq. 40
2
k
E = scale factor --- ( 1 – cos ( 2φ ) ) Eq. 41
2
You can also use the flat-bottomed function (Eq. 34) to apply J3
dihedral restraints to fit the results of NOE experiments. A plain
cosine form (Eq. 36) and a quadratic form (Eq. 29) are also avail-
able. The torson involving any four atoms can be restrained.
In FDiscover, the functional forms include a simple harmonic form
analogous to Eq. 32 and a piecewise continuous form like Eq. 33
with R interpreted as the angle, rather than the distance. Another
form is the periodic function of Eq. 42:
E = V [ 1 + cos ( nφ – φ 0 ) ] Eq. 42
E = Ki ( χ – χ0 ) 2 Eq. 43
b
x a
b
z c
Minimum-image model
Tip
For periodic systems in which nonbond interactions dominate,
the Ewald sum method (Ewald sums for periodic systems) is
preferred over the the minimum-image convention.
Simulation in bulk solvent The left side of Figure 9 shows a solute molecule surrounded by
enough solvent to occupy the volume (and shape) of a cube. A sim-
ulation carried out on this isolated cubic system is a poor approx-
imation of what would happen in a true bulk solvent environment.
For example, the solute can diffuse toward a surface or solvent
molecules can evaporate. To remedy this, on the right of Figure 9
the cube is replicated in three dimensions to form a 3 × 3 × 3 lattice
of identical cubes. This is a much better representation of bulk sol-
vent for the interior cube, because molecules near the surfaces now
interact with solvent in adjacent cubes. The imaged atoms are used
to calculate energies and forces on the real atoms in the interior
cube. The energies and forces on the imaged atoms themselves are
solute
Implications of minimum- Consider the implications of this model for a specific case. In
image model for calculat- Figure 10, molecule A1 is located near an edge of the square. (For
ing nonbond interactions simplicity, this discussion focuses on a two-dimensional lattice.) In
addition, eight images of A1 (A2–A9) are present in the adjacent
symmetrically related squares. Consider the interactions of mole-
cules A with molecules B. The closest image of B to A1 is actually
not B1, but rather B5. If molecules in the interior cell are allowed to
interact only with the molecule or molecular image closest to it,
this is called a minimum-image model. Each molecule interacts only
with those molecules and images within a distance of half the cell
size. The advantage of this approach is its simplicity. It is straight-
forward to compute energy between a given pair of molecules
without explicitly keeping track of the images in neighboring cells.
All periodic boundary algorithms imply a cutoff criterion, but the
minimum-image convention implies a maximum distance for this
cutoff of no more than half the cell dimensions.
For a description of the minimum-image convention, see also
Allen and Tildesley (1987).
A2 A3 A4
B2 B3 B4
A5 A1 A6
B5 B1 B6
A7 A8 A9
B7 B8 B9
Explicit-image model
A more general Simulation engines (Discover and CHARMm) can also use a more
approach—ghost mole- general approach by generating explicit images of the interior mol-
cules ecules, also called ghost molecules, which interact with the interior
molecules. These ghost molecules are replicated to as great a dis-
tance as necessary (but no farther than necessary) to satisfy the
desired potential energy cutoff criteria.
The left side of Figure 11 shows molecule A1 interacting with sev-
eral images of B (B1, B2, B3, B5) within the specified cutoff radius
(shown as a shaded circle centered on A1). A1 interacts with sev-
eral of its own images as well (A3, A5, A6, A8).
Cutoff distances and non- The right side of Figure 11 shows which molecules in the adjacent
bond interactions unit cells become explicit ghost molecules for a given cutoff dis-
tance. Not every molecule in an adjacent cell becomes a ghost.
However, if a cutoff distance that is longer than the cell length is
used, ghosts from unit cells beyond the nearest neighbor cells may
be included. As molecules (effectively, see below) move in and out
of the boundaries, the molecules that are ghosts can change. There-
fore, the ghost list is regenerated periodically.
A2 A3 A4 A2 A3 A4
B2 B3 B4 B2 B3 B4
ghost molecules
A5 A1 A6 A5 A1 A6
B5 B1 B6 B5 B1 B6
real
cutoff molecules
cutoff
A7 A8 A9 A7 A8 A9
B7 B8 B9 B7 B8 B9
Crystal simulations
Energies of crystals can be calculated and the lattice parameters a,
b, c, α, β, and γ can be optimized with Cerius2, CDiscover, and
CHARMm:
♦ In the Cerius2•OFF module, you can choose to optimize cell
dimensions and angles in 2D or 3D periodic systems or to con-
strain some of these coordinates. From the MINIMIZER card
(accessed from the OFF METHODS deck of cards), you can
access cell constraints options with the Constraints/Cell menu
item.
Crystal simulations are also available in several Cerius2•OFF
Instruments modules. For example, you can use the Crystal
Packer module to optimize crystals or calculate their energy
and can include minimization of periodic structures in a
Mechanical Properties run.
♦ In the Cerius2•Discover module, the Optimize Cell checkbox
in the Discover Minimize control panel is automatically
checked if the current model is periodic.
♦ In the Insight•Discover_3 module, crystal optimization is
requested by toggling Optimize_Cell in the Calculate/Mini-
mize parameter block. Crystal optimization is also available
within the Structure_Refine, Amorphous_Cell, and other
Insight II modules.
♦ In QUANTA, use the CHARMm/Periodic Boundaries menu
item to turn periodic boundary conditions on and obtain crystal
energies.
Availability
You may use different Typically, both van der Waals and Coulombic interactions are cal-
methods for van der culated by the same method and (if by the nonbond cutoff
Waals and electrostatic method) with the same nonbond list. However, different methods
interactions and parameters may be used for van der Waals and Coulombic
terms in CDiscover and (except for some operations) in
Cerius2•OFF and CHARMm. This allows you, for instance, to use
a large cutoff for electrostatic interactions and a smaller cutoff for
van der Waals interactions.
The van der Waals interaction potential is relatively short range
and dies out as 1 ⁄ r6. By 8–10 Å, the energy and forces are quite
small. Thus, using cutoffs to bring the van der Waals potential to
zero at about 10 Å can be a reasonable approximation. The Cou-
lombic interactions, on the other hand, die off as 1 ⁄ r, so even at
considerable distances the energy of interaction is not negligible.
But this depends on the model: except for a few formally charged
groups, most molecules are composed of neutral fragments with
dipoles and quadrupoles. Thus, in most models the major compo-
nent of the electrostatic interaction between molecules or parts of
molecules is a dipole–dipole interaction, which falls off as 1 ⁄ r3.
♦ To specify different methods for treating van der Waals and
Coulombic interactions in the Cerius2•Discover module, select
the Forcefield/Nonbond menu item in the DISCOVER card
and check the Treat VDW and Coulomb Separately check box
in the Discover Non-Bond control panel.
♦ Cerius2•OFF does not allow you to select different cutoffs for
Coulombic and van der Waals interactions if you are using a
non-Ewald method for both. However, you may independently
select an Ewald or non-Ewald method for either. If you do
select Ewald for both, you can independently set the cutoff and
convergence parameters for each.
Note
For models having 2D periodicity (e.g., built using the
Cerius2•Surface Builder) the Ewald method is available for the
Coulombic terms but not for the van der Waals terms.
1 4
1 3
1 2
2 2 3
Figure 12, Types of interactions usually excluded from nonbond
calculations
1–4 interactions and If 1–4 nonbond interactions in torsions are included in the non-
AMBER bond list, they may be scaled. For example, with the AMBER force-
field (as implemented in both Cerius2•OFF and Discover) these
nonbond interactions must be scaled by 0.50.
Scaling by 0.5 occurs by default with Cerius2 when AMBER is
loaded.
In the Insight•Discover module, you need to toggle the p1_4
parameter in the Parameters/Scale_Terms parameter block on and
enter 0.5 in the p14 parameter box,
The standalone version of the FDiscover program handles this
scaling with the following DSL command:
Important
This term is not set by default in Discover, even for the AMBER
forcefield, so you must remember to set the p1_4 parameter
either the first time that you run the Discover program from
Insight when using AMBER or in your command input file for
each standalone job that uses AMBER.
geometric: A ij = A ii A jj B ij = B ii B jj
Eq. 44
r ij = r ii r jj ε ij = ε ii ε jj
* *
arithmetic: * r ii + r jj Eq. 45
ε ij = ε ii ε jj r ij = -----------------
2
sixth-power:
*3 *3 *6 * 6 1/6
ε ii ε jj 2r ii r jj * r ii + r jj Eq. 46
ε ij = ---------------------------------------- r ij = -----------------------
*6
r ii + r jj
*6
2
(Halgren 1992). The 6th-power rule (not available with all force-
fields) yields even better results (Waldman and Hagler 1993).
van der Waals combina- With the Ewald method (Karasawa & Goddard 1989) (Ewald sums
tion rules and Ewald sums for periodic systems), the geometric mean leads to faster conver-
gence than the arithmetic mean.
In addition, because the Ewald sum calculation proceeds much
faster when only diagonal parameters are used, the Cerius2•OFF
Van Der Waals Preferences control panel includes an option to
ignore off-diagonals even when they are present (they are not
present in any of the Discover forcefields).
Important
A distance-dependent dielectric constant cannot be used on a
periodic model with the Ewald sum method (Ewald sums for
periodic systems).
Availability The dielectric constant can be changed and/or made distance
dependent in any of MSI’s simulation engines.
In Cerius2•FFE, the Coulombic control panel allows you to choose
the form of the Coulombic term—the term can be distance-depen-
dent, not distance-dependent, or corrected by an erfc term (see
Glass forcefield).
Special considerations for With the AMBER forcefield, in most applications a distance-
the AMBER forcefield dependent dielectric (ε = f (r)) should be used.
In Cerius2•OFF, the Epsilon value is 1.0 unless you change it in the
Coulomb Preferences control panel (which is accessed by selecting
the Energy Terms/Coulomb card menu item).
In the Insight•Discover_3 module, in the Specify/Nonbonds
parameter block you would click More, then set Dielectric to
Dist_Dependent and enter 4.0 for the Dielectric Value.
The equivalent BTCL command for the CDiscover program is
forcefield with the distance_dep keyword set to true and dielect
set to 4.0.
Nonbond cutoffs
Why read this section An energy expression such as Eq. 8, which is representative of cur-
rent forcefields, is computationally tractable only for systems with
relatively small numbers of atoms. The number of internal coordi-
nates grows linearly with the size of a model, so the computational
work involved in the first nine terms in Eq. 8 also grows linearly.
However, inspection of the final summation, which represents the
nonbond interactions, reveals a quadratic dependence on the
number of atoms in the system: If the system of interest has 1000
atoms, the nonbond summation has about 500,000 terms. If it has
10,000 atoms, the summation has 50,000,000!
Therefore, it is common to neglect or approximate the nonbond
interactions for widely separated pairs of atoms.
Choosing how to treat long-range nonbond interactions is an
important factor in determining the accuracy and the calculation
time of an energy evaluation.
Several cutoff methods are discussed below, and a review was
published by Brooks et al. (1985b). More recently, two other
methods—cell multipoles (Cell multipole method) and Ewald sums
(Ewald sums for periodic systems)—have also become available. You
should read all these sections to decide which method is best for
your model and computational problem.
Note
The same nonbond method(s)a and specifications should
generally be used for all energy calculations within a given
project.
aHowever, the method and/or specifications used for van der Waals
interactions may differ from those used for Coulombic interactions
(see You may use different methods for van der Waals and electro-
static interactions).
15
0
6 8 10 12 14 none
cutoff distance (Å)
Figure 13. Number of nonbond interactions as a function of cutoff
distance
The number of nonbond pairwise interactions (in millions) expected for a
5000-atom system as a function of cutoff distance. The time required to evalu-
ate the total energy of this system is approximately proportional to the number
of nonbond interactions.
Figure 14 shows how the van der Waals component of the non-
bond energy varies as a function of cutoff distance for an [Ala–
Pro–D-Phe]2 crystal. The van der Waals energy changes by 40% as
the cutoff distance is increased from 8 to 15 Å. The exact depen-
dence of the energy on the cutoff distance depends on the system
itself and should be calibrated for each new system.
–30
–50
–60
0 10 20 30 40
distance (r)
0.0
E(r) • S(r)
cutoff
CDiscover
spline width
buffer width
CUTDIS
FDiscover
SWTDIS
CUTOFF
spline-on distance
Cerius2•OFF
spline-off distance
buffer width
ron
CHARMm
roff
rcutoff
Figure 15. Application of a switching function
Application of a switching function; energy = E(r) · S(r). Variable names in MSI
simulation engines that relate to cutoffs are also illustrated. Thick dark curve =
the unmodified van der Waals potential; dashed curve = the switching function
S(r); grey curve = the resulting, switched potential.
ignored. The current defaults in the Open Force Field module set a
narrow on/off range that results in fast calculations. Using a
broader spline range gives more accurate results, but slower calcu-
lation.
1.0 r 2 ij < r 2 on
2
( r off – r ij ) 2 ( r 2 off + 2r 2 ij – 3r 2 on )
OFF switching function = ----------------------------------------------------------------------------------
- r 2 on < r 2 ij < r 2 off Eq. 47
( r 2 off – r 2 on ) 3
r 2 ij > r 2 off
0.0
Implementation in Dis- In the Discover program the switching function is defined by two
cover variables: the point where the function reaches zero and the range
over which the function decreases from one to zero (Figure 15).
The Discover program uses a fifth-order polynomial for the
switching function. It is formulated so that the first and second
derivatives are zero at both the inner and outer ends of the switch-
ing region. Thus, the interaction energy and its first and second
derivatives are continuous, although higher derivatives are not.
Implementation in CHARMm and Cerius2•MMFF offer two types of switching func-
CHARMm tions, which its documentation refers to as a switching function (not
the same as the Discover switching function) and a shifted potential.
Two variables corresponding to the ends of the switching regions
(ron and roff, Figure 15) are required to define the switching func-
tion. Depending on the value of rij, the following values are used
to multiply individual electrostatic or van der Waals energy terms:
1.0 r ij < r on
( r off – r ij ) 2 ( r off + 2r ij – 3r on ) r < r ij < r off
CHARMm switching function = -----------------------------------------------------------------------
- on Eq. 48
( r off – r on ) 3
r ij > r off
0.0
ual electrostatic and van der Waals terms in the energy function
are simply multiplied by this term:
r ij 2 2
1 – -------------
- Eq. 49
r cutoff
Charge group size and The size of a charge group, as defined by the greatest distance from
the cutoff distance the switching atom to another atom in the same group, must be
significantly smaller than the cutoff distances. Otherwise, an inter-
action between two atoms close to each other might be ignored
because the switching atoms of the two groups are farther apart
than the cutoffs. Typical groups are no more than 1–3 Å large, so
cutoffs larger than 7–8 Å are reasonable. However, some models
contain considerably larger groups.
The Discover program checks the size of the groups against the
cutoff distances, then outputs an error message and terminates if
the cutoffs are too short relative to the group size. If this happens,
you must either increase the cutoffs or define smaller groups.
Charge group neutrality… The Discover program also warns you about significantly non-
neutral groups. Some can be expected if the model contains for-
mally charged functional groups, such as protonated amines and
carboxylates. However, other non-neutral groups usually indicate
an error in group definitions.
… and defining or check- In Cerius2•Discover, you can specify the tolerance with which
ing charge groups neutrality is defined when you ask Discover to perform charge
grouping.
In Insight, charge groups and switching atoms are defined, edited,
and checked with the Forcefield/Groups parameter block, which
is found in the Builder, Biopolymer, and other modules. Potentials
and charges for the atoms must be fixed or accepted before defining
charge groups.
In CHARMm, you can edit charge groups in the RTF files with any
text editor. In PSF mode, every residue is a charge group.
Double cutoffs
The FDiscover program also incorporates an improvement over a
single cutoff distance called double cutoffs, or, as it is sometimes
called in dynamics, multiple timesteps. The nonbond interaction
potential at a distance is a smooth function that does not vary rap-
idly.
With double cutoffs, two cutoff distances—an inner and outer
one—are assigned. The two distances define an inner spherical
region and an outer shell around a given atom.
Tail corrections
Long-range van der For disordered periodic systems, contributions to the potential
Waals interactions in disor- energy and pressure from van der Waals interactions outside the
dered periodic systems cutoff can be written as:
ν ν ∞
∑ N ∑ ρ 4π∫ r g
1
∆U tail = --- α β
2
αβ ( r )U αβ ( r ) dr Eq. 50
2
α=1 β=1 rc
ν ν ∞
r dU αβ ( r )
∑ ∑ ∫
1
∆P tail = --- ρα ρ β 4π r 2 g αβ ( r ) ----------------------- dr Eq. 51
6 dr
α=1 β=1 rc
Cell-based cutoffs
CDiscover allows cell-based cutoffs for periodic systems. This is
another image-based method, in which the neighbor list is based
on a specified number of cell layers surrounding the central cell.
N
λi λj
E =
∑ λi Φi =
∑ ---------
R ijp
- Eq. 52
i=1 i>j
C C C C C
B B B B B B
C C
Af Af Af Af Af Af
B B B
Af An An An Af Af
Af An A0 An Af Af
B B B
Af An An An Af Af
C C
Af Af Af Af Af Af
B B B
Af Af Af Af Af Af
B B B B B B
C C
B B B B B B
C C C C C
∑D R ∑Q α α αβ R α R β
-–…
Z α αβ
Φ A ( r ) = ------p- – ------------------------
- + ---------------------------------- Eq. 53
f R Rp + 2 Rp + 4
∑T ∑T +…
(0) (1) 1 (2 )
ΦA ( r ) = T ( rA ) + α ( r A 0 )∆r α + --- αβ ( r A 0 )∆r α ∆r β
0 o 2
α αβ
Eq. 54
Improved computational The cell multipole method is an order-N method (Greengard and
performance and accu- Rokhlin 1987, Schmidt and Lee 1991, Ding et al. 1992). The time
racy savings with respect to an exact N 2 algorithm, as well as the
improved accuracy relative to using cutoffs, can be dramatic.
Table 12 shows results from several calculations on hemoglobin.
When the conventional method with 9.5-Å cutoffs is used, the
computational and setup times are greatly reduced, but at the cost
of a disturbingly large error (over 1% of the correct energies). The
last 6 lines of the table show results for second-, third-, and fourth-
order multipole expansions at two levels of computational accu-
racy. The short-range treatment becomes progressively better
towards the bottom of the table. However, the overall CPU time
increases. It is practical to achieve essentially exact results (within
a fraction of a kcal mol-1) in reasonable times.
For systems larger than hemoglobin, the improvement in perfor-
mance can be even more dramatic. For a system ten times larger,
the cell multipole method would take 3–10 minutes for the energy
evaluation, depending on the accuracy desired. The exact N 2 cal-
culation, in contrast, would take about three days!
energy eval-
level of calculation setupb uationc van der Waals Coulomb
exact pairwise calculation 468 2809 0.00 0.00
9.5-Å cutoff 12.6 30.2 1485 1359
coarsed, 2nd-order multi- 23.9 15.1 275 -26.0
pole
coarse, 3rd-order multi- 58.5 15.1 243 -25.0
pole
coarse, 4th-order multi- 199 16.1 243 -3.50
pole
finee, 2nd-order multipole 96.7 57.2 8.95 -10.6
fine, 3rd-order multipole 219 56.6 6.95 -2.50
fine, 4th-order multipole 718 57.7 0.24 -0.18
a
Relative to the exact pairwise calculation of the energy.
bTime required to set up atom lists and multipole expansions (overhead needed at
the beginning of a calculation and periodically during dynamics or minimization).
c
Time required for recurring evaluation of energy and gradients during a calculation.
dThat is, a reasonably accurate, fast calculation with low overhead.
e
That is, calculation with highest accuracy and greatest overhead.
Nonbond interaction Due to the nature of the cell multipole method, specific nonbond
energies interaction energies cannot be calculated unless you use the ESFF
forcefield. When this method is used with other forcefields, the
per-atom energy is calculated by using the cell multipole method,
and the nonbond interaction energy is calculated using the group-
based method. You can specify cutoffs for the group-based method
of nonbond analysis. A large cutoff in the group-based method
may give reasonably accurate energies compared with the cell
multipole method.
-100
-200
-300
35 40 45 50 55 60
cutoff (Å)
-32.6
17.338
-33.0
17.336
-33.4
5 10 15 20 25 30 35
cutoff (Å)
Figure 18. van der Waals energy vs. cutoff distance for NaCl
The graph shows the (solid lines) dispersive and (dashed line) repulsive portions
of the van der Waals energy as a function of the cutoff distance, as calculated
by the (thin lines) atom-based and (thick line) Ewald methods. The Ewald calcu-
lation was performed with CDiscover 3.1 to an accuracy of 1 e-6, which requires
a cutoff distance of 9.5 Å.
∑
1 A ij
S m = --- ---------------------------------- Eq. 55
2 ri – rj – RL m
L, i , j
A ij φ m ( r i – r j – R L ) A ij ( 1 – φ m ( r i – r j – R L ) )
∑ ------------------------------------------------- 2∑
1 1
S m = --- + --- ---------------------------------------------------------------
2 r –r –R m r –r –R m
i j L i j L
L, i , j L, i , j
Eq. 56
Here, the first term converges quickly, because φm(r) decreases rap-
idly. Ewald’s insight was that the second term can be Fourier trans-
formed to provide a rapidly converging sum over the reciprocal
lattice. The sum over L in Eq. 56 runs over all lattice vectors, but
the i = j terms must be omitted when L = 0.
The convergence func- The convergence functions are, for the electrostatic energy:
tions
∞
∫ exp( –s )ds
2
φ 1 = erfc ( ηr ) = 1 – erf ( ηr ) = ------- 2 Eq. 57
π
ηr
Optimizing computational The electrostatic convergence function φ1 was also used by Catlow
effort and Norgett (1976) and Karasawa and Goddard (1989). The disper-
sive convergence function φ6 was recommended and used by
Karasawa and Goddard. The convergence parameter η plays a
similar role in both cases. As η increases, the real-space sum con-
verges more rapidly and the reciprocal space sum converges more
slowly. (That is, a large η implies a heavy computational load for
reciprocal space, and a small η implies a heavy computational load
for real space.) Cutoffs must be adjusted accordingly, and process-
ing time is affected by the cutoffs. A value of η that balances pro-
2 2
∑ ∑ ∑ ∑
η erfc ( a ) 2π exp ( – b 2 )
--- q i q j ------------------ + ------ q i cos ( h • ri ) + q i sin ( h • ri ) ----------------------
-
EQ = 2 a Ω h2
L, i , j h≠0 i i
2
∑ ∑
η Π
– ------- q i2 – ------- η q i
π 2Ω
i i
Eq. 59
This chapter explains This chapter concentrates on the static information that can be
extracted from the potential energy surface, as well as on the algo-
rithms used for this purpose. The main areas that are covered—
minimization and harmonic vibration calculations—are usually
lumped together as molecular mechanics, to differentiate them from
molecular dynamics calculations (Molecular Dynamics), in which the
time evolution of the system is considered.
This chapter explains how minimization is implemented and pre-
sents general procedures for performing minimization calcula-
tions. To make the most effective use of minimization, you should
read this entire chapter, which includes:
General minimization process
Minimization algorithms
General methodology for minimization
Energy and gradient calculation
Vibrational calculation
Related information Forcefields and Preparing the Energy Expression and the Model focus
on the representation of the potential energy surface and the useful
ways that it can be biased through the addition of restraints and
constraints, as well as other information on preparing the model
for calculations.
Specific information For specific information on setting up and running minimizations
with the various MSI simulation engines, please see the relevant
documentation (see Available documentation).
Uses of minimization An important method for exploring the potential energy surface is
to find configurations that are stable points on the surface. This
means finding a point in the configuration space where the net
force on each atom vanishes. By adjusting the atomic coordinates
and unit cell parameters (for periodic models, if requested) so as to
reduce the model potential energy, stable conformations can be
identified.
Perhaps more important, the addition of external forces to the
model in the form of restraints (Preparing the Energy Expression and
Begin with the function This simple function illustrates the properties of the minimization
and an initial guess of its algorithms and captures the mathematical essence of the formula-
minimum tions. Every minimization begins with some energy expression
analogous to Eq. 60. In addition to an energy expression defining
the energy surface, a starting set of coordinates—an initial
guess—for (x,y) must be provided.
Figure 19 is a contour plot of the energy E in the (x,y) plane. Each
ellipse is spaced two energy units apart and represents a locus of
points having the same energy. (This is analogous to a contoured
topographical map.)
2.0
0.0 2 4 6 8 10 12 14 16 20
y
-2.0
-5.0 0.0 5.0
x
Figure 19. Energy contour surface of a simple function
An energy contour surface for the function x2 + 5y2. Each contour represents an
increase of two arbitrary energy units.
Line search
Before detailing the different algorithms, the concept of a line
search is introduced. Line searches are an implicit component of
most minimizers.
Most minimizers use line Minimizers usually have two major components. The more
searches generic part is the so-called line search, which actually changes the
coordinates to a new lower-energy structure. As an illustration,
consider Figure 20 in which the gradient direction from an arbi-
trary starting point has been superimposed on our elliptic func-
tion. The starting point (x0, y0) is defined as point a.
What is a line search? In simple terms, a line search amounts to a one-dimensional mini-
mization along a direction vector determined at each iteration. For
the path shown in Figure 20, it would be along derivative vector
(2x,10y), and the one-dimensional surface can be expressed para-
metrically in terms of coordinate α (see also Figure 21):
( x′, y′ ) = x + α ∂E , y0 + α
∂E Eq. 62
0 ∂x x 0, y 0
∂y x 0, y 0
where (x′, y′) are coordinates along the line away from the current
point (x0, y0) in the direction of the derivative at (x0, y0).
If the energy of these new points is calculated and plotted as a
function of α, the curve in Figure 21 is obtained.
2.0
b
a (x0,y0)
0.0
y
d
-2.0
-5.0 0.0 5.0
x
Figure 20. Energy surface for Eq. 60
The derivative vector from the initial point a (x0, y0) defines the line search direc-
tion. Note that the derivative vector does not point directly toward the mini-
mum. Compare this representation with that in Figure 21, where the line (b–a–c–
d) is searched in one dimension for the minimum. Note that the minimum (point
c) occurs precisely at the point where the derivative vector is tangent to the
energy contours, which implies that the subsequent derivative vectors are
orthogonal to the previous derivatives.
The minimum along α (that is, c) coincides with the point at which
the line is tangential to the energy contour. Because the maximum
derivative’s direction is perpendicular to the search line at this
point, each line search is orthogonal to the previous one. This is an
important property of line searches, which is also included in the
discussion of the conjugate gradient algorithm under Conjugate
gradient.
Efficiency and cost of Line searches do not depend on the algorithm that generated the
extensive line searches direction vector. The general strategy is to simply bracket the one-
dimensional minimum between two points higher in energy, for
example points b and d in Figure 21. Then, by a set of successive
iterations, the actual minimum is approached (e.g., starting at
point a, the first step might lead to b, then the direction might
reverse to lead to d and finally to c). Extensive line searches are
attractive because they extract all the energy from one direction
before moving on to the next. Also, the fact that the new deriva-
b
8
E(x′,y′)
a(x0,y0) d
7
c
6
-2 0 2 4 6
α
Figure 21. Cross section of the energy surface as defined by the
intersection of the line search path in Figure 20 with the energy surface
The independent variable α is a one-dimensional parameter that is adjusted so
as to minimize the value of the function E (x’, y’), where x’ and y’ are parame-
terized in terms of α in Eq. 62. Point a corresponds to the initial point (when α is
0), and point c is the local one-dimensional minimum. Points b and d, along with
a, bound the minimum and form the basis for an iterative search for the mini-
mum.
Minimization algorithms
Only minimization algorithms used in MSI’s simulation engines
(Table 14) are considered here:
Steepest descents
Conjugate gradient
Newton–Raphson methods
simulation engine
algorithm variant
CHARMm Discover OFF MMFF93
steepest descents √ √ √ √
conjugate gradient Polak–Ribiere √ √
Fletcher–Reeves √ √ √ √
Powell √ √
Newton–Raphson full, iterative √ √ √ √
BFGS (quasi) √ √
DFP (quasi) √ √
truncated √ √ √
ABNR √ √ √
Steepest descents
In the steepest-descents method, the line search direction is
defined along the direction of the local downhill gradient –∇
E(xi, yi). Figure 22 shows the minimization path followed by a
steepest-descents approach for the simple quadratic function. As
expected, each line search produces a new direction that is perpen-
dicular to the previous gradient; however, the directions oscillate
along the way to the minimum. This inefficient behavior is charac-
teristic of steepest descents, especially on energy surfaces having
narrow valleys.
Increased efficiency with What would happen if the line search were eliminated and the
truncated line searches position would simply be updated any time that the trial point
along the gradient had a lower energy? The advantage would be
that the number of function evaluations performed per iteration
would be dramatically decreased. Furthermore, by constantly
2.0
0.0
y
-2.0
-5.0 0.0 5.0
x
Figure 22. Minimization path following a steepest-descents path
When complete line searches starting from point a are used, the minimum is
reached in about 12 iterations. Here, where a rigorous line search is carried out,
approximately 8 function evaluations are needed for each line search using a
quadratic interpolation scheme. Note how steepest descents consistently over-
shoots the best path to the minimum, resulting in an inefficient, oscillating trajec-
tory.
2.0
0.0
y
-2.0
-5.0 0.0 5.0
x
Figure 23. Minimization path following a steepest-descents path without
line searches
The searching starts from point a and converges on the minimum in about 12
iterations. Although the number of iterations is slightly larger than in Figure 22,
the total minimization is five times faster since, on average, each iteration uses
only 1.3 function evaluations. Note that, in most applications in molecular
mechanics, the function evaluation is the most time-consuming portion of the
calculation.
Tip
The conjugate gradient method (below) and the iterative and
quasi Newton–Raphson methods assume that the conformation
is close enough to a local minimum that the potential energy
surface is very nearly quadratic. Hence, steepest descents
should generally be used for the first 10–100 steps of
minimization (depending on the size of the model and how
distorted its starting conformation is). Please see also When to
use different algorithms.
Conjugate gradient
The reason that the steepest-descents method converges slowly
near the minimum is that each segment of the path tends to reverse
progress made in an earlier iteration. For example, in Figure 22,
each line search deviates somewhat from the ideal direction to the
minimum. Successive line searches correct for this deviation, but
they cannot efficiently correct because each direction must be
orthogonal to the previous direction. Thus, the path oscillates and
continually overcorrects for poor choices of directions in earlier
steps.
Increasing the efficiency It would be preferable to prevent the next direction vector from
of line searches by con- undoing earlier progress. This means using an algorithm that pro-
trolling the choice of new duces a complete basis set of mutually conjugate directions such
direction that each successive step continually refines the direction toward
the minimum. If these conjugate directions truly span the space of
the energy surface, then minimization along each direction in turn
must by definition end in arriving at a minimum. The conjugate
gradient algorithm constructs and follows such a set of directions.
In conjugate gradients, hi+1, the new direction vector leading from
point i+1, is computed by adding the gradient at point i+1, gi+1, to
the previous direction hi scaled by a constant γi:
hi + 1 = gi + 1 + γ i hi Eq. 63
Polak–Ribiere method where γi is a scalar that can be defined in two ways. In the Polak–
Ribiere method, γi is defined as:
( g i + 1 – g i )g i + 1
γ i = --------------------------------------- Eq. 64
g i ⋅ gi
gi + 1 ⋅ gi + 1
γ i = ---------------------------- Eq. 65
g i ⋅ gi
Tip
The conjugate gradient method can be unstable if the
conformation is so far away from a local minimum that the
potential energy surface is not nearly quadratic. Steepest
descents (Steepest descents) should generally be used for the first
10–100 steps of minimization. Please see also When to use
different algorithms.
Newton–Raphson methods
r min = r 0 – A – 1 ( r 0 ) ⋅ ∇E ( r 0 ) Eq. 66
r i = r i – 1 – A – 1 ( r i – 1 ) ⋅ ∇E ( r i – 1 ) Eq. 67
Drawbacks of pure New- As elegant as this algorithm appears, its application to molecular
ton–Raphson method modeling has several drawbacks. First, the terms in the Hessian
matrix are difficult to derive and are computationally costly for
molecular forcefields. Furthermore, when a structure is far from
the minimum (where the energy surface is anharmonic), the mini-
mization can become unstable.
For example, when the forces are large but the curvature is small,
such as on the steep repulsive wall of a van der Waals potential, the
algorithm computes a large step (a large gradient divided by the
small curvature) that may overshoot the minimum and lead to a
point even further from the minimum than the starting point.
Thus, the method can diverge rapidly if the initial forces are too
high (or the surface too flat).
Finally, calculating, inverting, and storing an N × N matrix for a
large system can become unwieldy. Even taking into account that
the Hessian is symmetric and that each of the tensor components
is also symmetric, the storage requirements scale as approximately
3N 2 for N atoms. Thus, for a 200-atom system, 180,000 words are
required. The Hessian alone for a 1,000-atom system already
approaches the limits of a Cray-XMP supercomputer, and a
10,000-atom system is currently intractable.
Pure Newton–Raphson is reserved primarily for calculations
where rapid convergence to an extremely precise minimum is
required, for example, from initial derivatives of 0.1 kcal mol-1 Å-1
to 10-8 kcal mol-1 Å-1. Such extreme convergence is necessary
when performing vibrational normal mode analysis, where even
small residual derivatives can lead to errors in the calculated
vibrational frequencies.
Tip
The iterative Newton–Raphson method can be unstable if the
conformation is so far away from a local minimum that the
potential energy surface is not nearly quadratic. Steepest
descents (Steepest descents) should generally be used for the first
10–100 steps of minimization. Please see also When to use
different algorithms.
(which includes the BFGS and DFP methods) and the truncated
Newton methods. These variants, as well as others, are character-
ized by the use of the general algorithm shown in Figure 24.
Ak pk + gk < φk gk
xk + 1 = xk + λ k pk
7. Go to Step 2.
T
δδ T B k γγ B k
Bk + 1 = B k + --------- – --------------------- Eq. 68
δT γ γT Bkγ
T T T
γ B k γ δδ T δγ B k + B k γδ
Bk + 1 - – -------------------------------------
= B k + 1 + ----------------- -------- Eq. 69
δT γ δT γ δT γ
Tip
The quasi Newton–Raphson method can be unstable if the
conformation is so far away from a local minimum that the
potential energy surface is not nearly quadratic. Steepest
descents (Steepest descents) should generally be used for the first
10–100 steps of minimization. Please see also When to use
different algorithms.
p j + 1 = pj + γj d j
c. Test for convergence of the conjugate-gradient inner loop:
if:
rj + 1 ≤ φ gk
then:
pk = pj + 1
and go to Step 4.
d. Begin next iteration of conjugate gradients.
Solve for Mzk = rk for zk and construct new conjugate direction:
d j + 1 = zj + 1 + βj d j
zj + 1
βj = r jT+ 1 ----------
-
r jT z j
Prerequisites One of the most important steps in any simulation is properly pre-
paring the model to be simulated. Calculations on the fastest com-
puter running the most efficient minimization algorithm may be
worthless if the hydrogen is put on the wrong nitrogen or an
important water molecule is omitted.
Unfortunately, it is impossible to provide a single recipe for a suc-
cessful model—too much depends on the objectives and expecta-
tions of each calculation. Are energies to be compared
Failure to converge Also, note that the derivation invokes a quadratic approximation.
For nonharmonic systems, the conjugate gradient method can
exhaustively minimize along the conjugate directions without
converging. This condition indicates that the minimizer may have
gotten stuck at a saddle point. If this occurs, you can restart the
algorithm. Several minimizations may be required. For a detailed
discussion of this algorithm, see the excellent text by Press et al.
(1986) or the somewhat more formal treatment by Fletcher (1980).
Convergence criteria
Mathematical definition In the literature a wide variety of criteria have been used to judge
minimization convergence in molecular modeling. Mathemati-
cally, a minimum is defined as the point at which the derivatives
of the function are zero and the second-derivative matrix is posi-
tive definite. Nongradient minimizers can use only the increment
in the energy and/or coordinates as criteria. In gradient minimiz-
ers, derivatives are available analytically and should be used
directly to assess convergence.
Application to chemical In a molecular minimization, the atomic derivatives may be sum-
models marized as an average, a root-mean-square (rms) value, or the
largest value. The average, of course, must be an average of the
absolute values of the derivatives, because the distribution of
derivatives is symmetric about zero. A rms derivative is a better
measure than the average, because it weights larger derivatives
more, and it is therefore less likely that a few large derivatives
would escape detection, which can occur with simple averages.
Regardless of whether you choose to report convergence in terms
of the average or rms values of the derivatives, you should always
check that the maximum derivative is not unreasonable. There can
be no ambiguity about the quality of the minimum if all deriva-
tives are less than a given value.
How close to absolute The more difficult question is, What value of the average or rms
convergence is good derivative constitutes convergence? The specific value depends on
enough? the objective of the minimization. If you simply want to relax over-
lapping atoms before beginning a dynamics run, minimizing to a
maximum derivative of 1.0 kcal mol-1 Å-1 is usually sufficient.
However, to perform a normal mode analysis, the maximum
derivative must be less than 10-5, or the frequencies may be shifted
by several wavenumbers.
Local or global minimum? There is no guarantee that the minimum you find is necessarily a
global minimum.
Small models can be minimized to a global minimum. However,
multiple minimizations from different starting conformations
should be run to confirm that a global minimum has indeed been
found.
Vibrational calculation
This section includes:
Application of minimization to vibrational theory
Vibrational frequencies
General methodology for vibrational calculations
Harmonic vibrational fre- The vibrational frequencies and modes of a molecule are strictly
quencies obtained from dynamic properties. However, it is possible to calculate the har-
an equilibrium geometry monic vibrational frequencies of a model from just information at
its equilibrium geometry by expanding the potential energy sur-
face as a Taylor series, truncating after the second term, and con-
sidering infinitesimal displacements. This harmonic
approximation usually gives a good description of the true fre-
quencies and normal modes and can be valuable for tasks ranging
from evaluating the quality of a forcefield to understanding vibra-
tional shifts induced by conformational changes or other interac-
tions. The harmonic vibrational frequencies also can be used for
zero-point vibrational corrections and for deriving vibrational free
energy contributions. These effects can be important in comparing
conformational energies and rotational barrier heights.
Uses of vibrational calcu- Beyond these considerations, the vibrational frequencies can be
lations used for two classes of problems:
♦ The first is for determining the shape of the potential energy
surface; that is, the characterization of stable points as minima,
transition states, or other points. For this purpose, the question
of forcefield accuracy is less important. The qualitative, rather
than quantitative, shape of the surface is all that is important.
♦ The second use is for comparison with experimental results.
The vibrational frequencies and thermodynamic corrections
depend strongly on the forcefield as well as on the fundamental
harmonic approximation invoked. By nature, low-frequency
modes are less harmonic. The torsion and nonbond interac-
tions, which dominate low-frequency modes, are fundamen-
tally anharmonic; hence the interpretation of the calculated
low-frequency modes should take this into account. Unfortu-
nately, these low-frequency modes make the largest contribu-
tions to the vibrational entropy.
∑
2 2 2
1
m i ∆x + ∆y + ∆z
d d d
T = --- Eq. 70
2 dt dt dt
i=1
qi = m α ∆x α Eq. 71
Simplified kinetic energy where mα is the mass of the atom associated with the α coordinate,
of nuclei and ∆xα runs over the y and z coordinates, as well as x, then the
kinetic energy has the following simple form:
3N
∑
2
1 dq i
T = --- Eq. 72
2 dt
i=1
The second term in a Tay- When the potential energy of the system is expanded as a Taylor
lor series is needed to series in the same coordinates, it yields:
obtain vibrational infor-
mation 3N 3N
3N
∑
1 δ2V
V = --- --------------
- q i q j Eq. 74
2 δq i δq j 0
i ,j = 1
Combining energy and Using this approximation of the potential energy in Newton’s
motion and solving for the equations of motion (Eq. 4) yields the following simultaneous sec-
mass-weighted coordi- ond-order differential equations:
nates
3N
2
∑
d qi δ2 V
--------------
+ δq δq- q j = 0 i = 1 ,2 , … ,3N Eq. 75
d t2 i j 0
d=1
q i = A i cos ( λ 1 / 2 t + δ ) Eq. 76
Numerically solvable form where the Ai are related to the relative amplitudes of the vibra-
of the function tional motion, λ1⁄2 is proportional to the vibrational frequency, and
δ is a phase. Substituting Eq. 76 in Eq. 75 yields a set of algebraic
equations:
3N
∑ δ2V
--------------
δq δq- – δ ij λ A i = 0
i j 0
j = 1 ,2 , … ,3N Eq. 77
i=1
Vibrational frequencies
Eigenvalues converted to The simulation engine determines vibrational frequencies by cal-
vibrational frequencies culating the second derivative matrix, mass weighting it, and then
diagonalizing it to obtain the eigenvalues. These eigenvalues are
then converted to vibrational frequencies in wavenumbers as fol-
lows:
νi = F λi Eq. 78
Evaluating the quality of where the conversion factor F converts the units from kcal mol-1 to
the calculation wavenumbers. Of the 3N coordinates used to calculate the energy
and vibrational frequencies, six correspond to net translations and
rotations of the model (five for linear systems). These six modes
have no restoring force and therefore have vibrational frequencies
of zero for a minimized structure. Due to numerical inaccuracies,
the simulation engine reports these frequencies with small values,
which are typically less than 0.1 cm-1. If the structure is not per-
fectly minimized, the first-order terms in the Taylor expansion of
the potential surface in Eq. 73 do not vanish. In turn, they intro-
duce terms that couple the net rotations of the model with the
internal motions and both perturb the internal vibrational fre-
quencies and give apparent frequencies for the three rotations.
Thus, the magnitude of the six “zero” frequencies is a good indica-
tion of the quality of the calculation.
Transition states
The model must be opti- For calculating vibrational frequencies, the model must be mini-
mized before doing a mized and the gradients must be zero. This does not mean that the
vibration calculation configuration of the model must be at a minimum, but rather that
it must be at a stable point on the surface. If the structure is not at
a minimum, but rather is at a saddle point or transition state in one
or more directions, this is reflected in the eigenvalues and the
reported vibrational frequencies. For a saddle point, at least one
eigenvalue is negative, which means that the curvature of the sur-
face along at least one normal mode is negative. By convention, the
imaginary frequencies for such modes are reported as negative.
Therefore, the reported vibrational frequencies describe the char-
acter of the stable point on the surface. If all frequencies are real, it
is a minimum; if one frequency is imaginary, the structure is in a
simple transition state; if two or more frequencies are imaginary, a
double or more complicated transition state is indicated. The nor-
mal modes corresponding to the frequencies can be analyzed to
understand the reaction path going through such a transition state.
Thermodynamics
Quantum mechanical The quantum mechanical solution for the vibrational energy of a
solution… set of uncoupled harmonic oscillators, which corresponds to the
classical treatment outlined above, is:
E vib =
∑ n + 1
--
-
i 2 i
hν
Eq. 79
…used to correct the where the summation is over all the vibrational frequencies, ni is
vibrational energy deter- the vibrational quantum number for each vibration, h is Planck’s
mined with a forcefield constant, and νi is the vibrational frequency. This leads to the fol-
lowing correction to the classical forcefield energy:
∑ --2- + ------------------------
1 1
E vib = - hν i Eq. 80
e hν i /kT –1
i
Free energy correction where k is the Boltzmann constant and T is the temperature. The
first term, hνi ⁄ 2, is the zero-point correction; the second term cor-
rects for the average thermal population of vibrational levels at the
temperature T. This leads to a vibrational free energy correction of:
∑ -------2 - + kT ln 1 – e
hν i – hν i /kT
A vib = Eq. 81
Related information Forcefields and Preparing the Energy Expression and the Model focus
on the representation of the potential energy surface and the useful
ways that it can be biased through the addition of restraints and
Integration algorithms
This section includes:
Introduction
Criteria of good integrators in molecular dynamics
Integrators in MSI simulation engines
Introduction
Newton’s equation of At its simplest, molecular dynamics solves Newton’s familiar
motion applied to atoms equation of motion:
Fi ( t ) = mi ai ( t ) Eq. 83
2
∂V ∂ ri
– = mi 2 Eq. 84
∂ri ∂ti
What is a trajectory? Notice that classical equations of motion are deterministic. That is,
once the initial coordinates and velocities are known, the coordi-
simulation engine
integrator
CHARMm Discover OFF
Verlet leapfrog √ √a
√
Verlet velocity √ √b
ABM4 √2
Runge–Kutta–4 √2
a
FDiscover only, not in CDiscover.
bCDiscover only, not in FDiscover.
ment entry box and select Execute. Be sure that you insert this
stage at the correct point in your command input file.
♦ The Insight•Discover module always uses the Verlet leapfrog
integrator.
♦ CHARMm allows you to choose between the Verlet leapfrog
and velocity methods only when run in standalone mode.
∆t 2 a ( t )
r ( t + ∆t ) = r ( t ) + ∆tv ( t ) + ------------------
2
f ( t + ∆t )
a ( t + ∆t ) = --------------------
m
1
v ( t + ∆t ) = v ( t ) + --- ∆t [ a ( t ) + a ( t + ∆t ) ]
2
ABM4 integrator
ABM4, which stands for Adams–Bashforth–Moulton fourth order,
is a predictor and corrector method. It is a fourth-order method,
meaning that the truncation error is to the fifth order of the
timestep used.
This method requires two energy evaluations per step and has to
make use of the results of the previous three steps. It is thus not self
starting—the first three steps are generated by the Runge–Kutta
method. More memory has to be used, because previous informa-
tion has to be stored.
ABM4’s algorithm The algorithm is as follows:
Let:
y = r ( t ), v ( t ) and y′ = v ( t ), a ( t )
predicted ∆t
y1 = y 0 + ------ ( 55y 0 ′ – 59y – 1 ′ + 37y – 2 ′ – 9y – 3 ′ ) + O ( ∆t 5 )
24
corrected ∆t
y1 = y 0 + ------ ( 9y 1 ′ + 19y 0 ′ – 5y – 1 ′ + y – 2 ′ ) + O ( ∆t 5 )
24
Runge–Kutta-4 integrator
Robust, but disadvan- Runge–Kutta-4 stands for the fourth-order Runge–Kutta method,
tages which is one of the oldest numerical methods for solving ordinary
differential equations. The method is self starting but requires four
energy evaluations per step.
From testing done at MSI, the timestep has to be very small. This
is thus not a very suitable integrator for molecular simulation.
However, the method is very robust, meaning that it can deal with
almost all kinds of equations, including stiff ones. This integrator
is used to generate the trajectory for the first three steps for ABM4.
Since we do not recommend using this integrator, the algorithm is
not presented here. Details can be found in Press et al. 1986.
Appropriate for the inte- The timestep must also be appropriate to the integrator. For the
grator ABM4 method, the timestep should be about half that needed for
the Verlet algorithm. The Runge–Kutta-4 method seems to require
a much smaller timestep than the other methods.
Setting the timestep To specify the length of the timestep:
♦ In Cerius2•OFF, go to the DYNAMICS SIMULATION card in
the OFF METHODS deck of cards. Click the Run menu item to
access the Dynamics Simulation control panel. Enter the
desired time step (in ps) in the Dynamics Time Step entry box.
♦ In Cerius2•Discover, click the Run menu item in the DIS-
COVER card to access the Run Discover control panel. Set the
Task popup to Dynamics and click the More… pushbutton to
the right of the Task popup to open the Discover Dynamics
control panel. Enter values for two of the Total time, Steps, and
Time step entry boxes (the third value is computed from the
other two) in the Equilibration and Production sections of the
latter control panel.
♦ In the Insight•Discover_3 module, select the Calculate/
Dynamics command. Toggle More on to access additional con-
trols, and change the value in the Time Step fs entry box.
♦ In the Insight•Discover module, select the Parameters/Dynam-
ics command. Change the value (in fs) in the Time Step entry
box.
♦ In QUANTA, Choose the CHARMm/Dynamics Options menu
item. You can change the Time Step in any of the setup dialogs
that are accessed by clicking a radio button and clicking OK.
Integration errors
If the chosen timestep is too small, no harm is done, except for the
waste of computer time. However, if the timestep is too large for
the calculation conditions, the simulation can “blow up”.
Two examples illustrate how the timestep, temperature, and inte-
gration algorithm affect the results. The first example is a simula-
tion of the collision of two hydrogen atoms travelling towards
each other. The second is an examination of energy conservation in
0.02
0.00
-0.01
300K
1 fs timestep
-0.02
2 3 4 5
H–H distance (Å)
Figure 26. Numerical integration of energy from molecular dynamics
hydrogen-collision trajectory, 1 fs timestep
The integrated energy calculated numerically from a dynamics trajectory of
two colliding hydrogen atoms (circles) is compared with the analytical energy
curve (thick line). Simulation done with FDiscover.
Shorter timesteps mean Figure 27 shows the same curve as Figure 26, but with timesteps of
more computational cost 0.33 and 0.10 fs. Both give better results than 1.0 fs, but it is not
clear whether the extra time required to calculate the smaller
timesteps is worthwhile.
A very large timestep The consequences of too large a time step are much more dramatic.
leads to artifactual Doubling the time step from 1 to 2 fs results in an unusual artifact
behavior for the hydrogen system (Figure 28). In this case, the integration
error affects not only the potential energy, but the kinetic energy as
well. Momentum is removed, so that the hydrogens no longer
have the velocity needed to escape after the collision. The atoms
are trapped forever (barring an inverse error that could impart
momentum). The atoms now vibrate back and forth (only 2 cycles
are plotted in Figure 28), and each cycle incurs an additional inte-
gration error.
An even higher timestep Increasing the time step another factor of 2 to 4 fs (Figure 29)
can cause the system to finally causes the system to “blow up”. The timestep is so long that
explode the atoms deeply interpenetrate each other’s steeply repulsive
wall between steps. The resulting force is now so large that the
0.02
300K
0.33 fs timestep
0.01
-0.01
300K
0.1 fs timestep
0.01
0.00
-0.01
-0.02
2 3 4 5
H–H distance (Å)
Figure 27. Numerical integration of energy from molecular dynamics
hydrogen-collision trajectory, 0.33 and 0.1 fs timesteps
Energy integration errors decrease with smaller time steps. Compared to 0.016
kcal error with 1 fs time steps, the 0.33 fs time step has a 0.006 error, and the 0.1
fs time step a 0.001 error. The cost for increased accuracy is the computational
burden to compute more steps. For most simulations, a 1-fs time step is a good
compromise between numerical accuracy and computational efficiency. Sim-
ulation done with FDiscover.
atoms fly off at a speed of about 1 Å fs-1 (or 105 m s-1). An equiva-
lent temperature would be hundreds of thousands of degrees.
Effect of temperature To complete the analysis of integration errors, it is instructive to
compare the effects of increasing kinetic energy on the stability of
0.10 300K
2 fs timestep
0.08
0.04
0.02
0.00
-0.02
2 3 4 5
H–H distance (Å)
Figure 28. Numerical integration of energy from molecular dynamics
hydrogen-collision trajectory, 2 fs timestep
A 2-fs time step causes the rebounding force to be underestimated, robbing the
colliding Hs of sufficient escape velocity and resulting in the two Hs being
“bound” by their van der Waals forces. Simulation done with FDiscover.
0.20
energy (kcal mol-1)
0.15
300K
0.10 4 fs timestep
0.05
0.00
-0.05
3 2 4 5
H–H distance (Å)
Figure 29. Numerical integration of energy from molecular dynamics
hydrogen-collision trajectory, 4 fs timestep
With a time step of 4 fs, the Hs travel too far in a single step, interpenetrating
each other’s van der Waals radii before the forces are recalculated. By this time,
the forces are so large that the Hs are flung apart at a temperature equivalent
to hundreds of thousands of degrees. Simulation done with FDiscover.
0.04
0.03
energy (kcal mol-1)
0.02
0.01
0.00
-0.01
-0.02
2 3 4 5
H–H distance (Å)
Figure 30. Integration errors for hydrogen-collision trajectories at several
temperatures
Integration errors observed for an H–H collision for an initial velocity equal to the
mean velocity appropriate for 300 K (squares), 1200 K (circles) and 30,000 K (tri-
angles). Simulation done with FDiscover.
Table 18. Energy conservation for different timesteps with the Verlet
velocity and ABM4 integrators
Run conditions: 10,000 fs, constant-energy (NVE), harmonic oscillator, initial
energy 0.296 kcal mol-1, CDiscover 94.0.
Statistical ensembles
You can control the tem- Integrating Newton’s equations of motion allows you to explore
perature and pressure the constant-energy surface of a system. However, most natural
phenomena occur under conditions where a system is exposed to
external pressure and/or exchanges heat with the environment.
Under these conditions, the total energy of the system is no longer
conserved, and extended forms of molecular dynamics are
required.
Purpose of the calculation Several methods are available for controlling temperature and
pressure. Depending on which state variables (the energy E,
enthalpy H (i.e., E + PV), number of particles N, pressure P, stress
S, temperature T, and volume V) are kept fixed, different statistical
ensembles can be generated. A variety of structural, energetic, and
dynamic properties can then be calculated from the averages or
the fluctuations of these quantities over the ensemble generated.
Available thermodynamic Both isothermal (exchange heat with a temperature bath to main-
ensembles tain a constant thermodynamic [not kinetic] temperature) and adi-
abatic (do not exchange heat) ensembles are available:
simulation engine
ensemblea
CHARMm Discover OFF
Constant temperature, constant volume (NVT) √ √ √
Constant temperature, constant pressure (NPT)b √c √ √
Constant temperature, constant stress (NST)2 √d √
Constant energy, constant volume (NVE) √ √ √
Constant pressure, constant enthalpy (NPH)2 √4 √
Constant stress, constant enthalpy (NSH)2 √4 √
a
In all
ensembles, the number of particles is conserved.
bOnly for periodic systems, because volume is undefined in nonperiodic systems. For
all space-group symmetries unless otherwise noted.
cOnly for cubic, orthorhombic, and triclinic unit cells.
dCDiscover only, not in FDiscover.
Choosing the thermody- To access the controls used for specifying the thermodynamic
namic ensemble ensemble:
♦ In Cerius2•OFF, go to the DYNAMICS SIMULATION card on
the OFF METHODS deck of cards. Click the Run card menu
item to access the Dynamics Simulation control panel. Select
the radio button next to the desired ensemble. You can access
additional controls relevant to each ensemble by clicking the
Preferences… button to the right of the ensemble.
♦ In Cerius2•Discover, click the Run menu item on the DIS-
COVER card to access the Run Discover control panel. Set the
Task popup to Dynamics and click the More… pushbutton to
the right of the Task popup. The controls available depend on
what Ensemble and Thermostat you choose and on whether
the current model is periodic or not.
♦ In the Insight•Discover_3 module, select the Calculate/
Dynamics command. Only the ensembles appropriate to your
model system (periodic or nonperiodic) are displayed in the
parameter block. Toggle More on to access additional controls
relevant to the chosen ensemble.
NVE ensemble
Some energy drift The constant-energy, constant-volume ensemble (NVE), also
known as the microcanonical ensemble, is obtained by solving the
standard Newton equation without any temperature and pressure
control. Energy is conserved when this (adiabatic) ensemble is
generated. However, because of rounding and truncation errors
during the integration process, there is always a slight fluctuation
or drift in energy.
When the Verlet leapfrog integrator is used, only r (t) and v (t – 1 ⁄ 2
∆t) are known at each timestep. Thus, the potential and kinetic
energies at each timestep are also half a step out of synchrony.
Although the difference between the kinetic energies half a
timestep apart is small, this can also contribute to the fluctuation
in the total energy.
Although the temperature is not controlled during true NVE
dynamics, you might want to use NVE conditions during the
equilibration phase (Stages and duration of dynamics simulations) of
your simulation. For this purpose, Cerius2•Discover and
Cerius2•Dynamics Simulation allow you to hold the temperature
within specified tolerances by periodic scaling of the velocities.
When to use it True constant-energy conditions (i.e., without temperature contol)
are not recommended for equilibration because, without the
energy flow facilitated by temperature control, the desired tem-
perature cannot be achieved.
However, during the data collection phase, if you are interested in
exploring the constant-energy surface of the conformational space,
or for other reasons do not want the perturbation introduced by
temperature- and pressure-bath coupling, this is a useful ensem-
ble.
NVT ensemble
The constant-temperature, constant-volume ensemble (NVT), also
referred to as the canonical ensemble, is obtained by controlling the
thermodynamic temperature. Direct temperature scaling should
be used only during the initialization stage (Stages and duration of
dynamics simulations), since it does not produce a true canonical
ensemble (it is not truly isothermal). Any of the other temperature-
control methods available (How temperature is controlled) is used
during the data collection phase.
When to use it This is the appropriate choice when conformational searches of
models are carried out in vacuum without periodic boundary con-
ditions. (Without periodic boundary conditions, volume, pressure,
and density are not defined and constant-pressure dynamics can-
not be carried out.)
Even when periodic boundary conditions are used, if pressure is
not a significant factor, the constant-temperature, constant-vol-
ume ensemble provides the advantage of less perturbation of the
trajectory, due to the absence of coupling to a pressure bath.
However, only the size, and not the shape, of the unit cell can be
changed with the Berendsen and Anderson methods (Berendsen
method of pressure control and Andersen method of pressure control).
Stress can be controlled by the Parrinello–Rahman method (Par-
rinello–Rahman method of pressure and stress control), since it allows
both the cell volume and its shape to change.
Temperature can be controlled by any method available (How tem-
perature is controlled) (except, of course, the temperature scaling
method, since it is not truly isothermal).
When to use it NPT is the ensemble of choice when the correct pressure, volume,
and densities are important in the simulation. This ensemble can
also be used during equilibration to achieve the desired tempera-
ture and pressure before changing to the constant-volume or con-
stant-energy ensemble when data collection starts.
Results The NST ensemble is particularly useful if you want to run a sim-
ulation at incremented tensile loads to study the stress–strain rela-
tionship in polymeric or metallic materials.
If the forcefield being used yields a high pressure at the experi-
mental volume, it may be more realistic to simulate at the experi-
mental pressure rather than the experimental volume. High
simulated pressure is a sign that the system is unduly compressed,
which restricts atomic motions, artefactually slowing down the
dynamic relaxations.
NSH dynamics, you might want to use these conditions during the
equilibration phase (Stages and duration of dynamics simulations) of
your simulation. For this purpose, Cerius2•Discover and
Cerius2•Dynamics Simulation allow you to hold the temperature
within specified tolerances by periodic scaling of the velocities.
Results The natural response functions (specific heat at constant pressure,
thermal expansion, adiabatic compressibility, and adiabatic com-
pliance tensor) are obtained (Equilibrium thermodynamic properties)
from the proper statistical fluctuation expressions of kinetic
energy, volume, and strain (Ray 1988).
Caution
In practice, obtaining accurate fluctuations to calculate physical
quantities is difficult, and this approach should be used with
caution.
∫
A = OLP T → ∞ --- A ( t ) dt Eq. 85
T
Time averaging for first- Through time averaging, you can calculate the first-order proper-
order properties ties of a system (such as the internal energy, kinetic energy, pres-
sure, and virial). Similarly, using microscopic expressions in the
form of fluctuations of these first-order properties, you can also
calculate thermodynamic properties of a system. These include the
specific heat, thermal expansion, and bulk modulus.
In the thermodynamic limit, the first-order properties obtained in
one ensemble are equivalent to those obtained in other ensembles
(differences are on the order of 1/N).
Ensemble-dependent However, second-order properties such as specific heats, com-
second-order properties pressibilities, and elastic constants differ between ensembles. For
example, the specific heat at constant pressure differs from the spe-
cific heat at constant volume.
Therefore, it is important to use the appropriate ensemble when
performing simulations to obtain these properties.
Temperature
This section includes:
How temperature is calculated
How temperature is controlled
mv 2
m 3 / 2 – ----------
f ( v )dv = ----------- e 2kT 4πv 2 dv Eq. 86
2πkt
This well known formula expresses the probability f (v) that a mol-
ecule of mass m has a velocity of v when it is at temperature T.
Figure 31 shows this distribution at various temperatures.
3
probability (¥ 1000) 100K
2
300K
600K
1
1000K
0
1000 0 2000
speed (m s ) -1
– mvx2
m 1 / 2 -------------
g ( vx )dvx = ------------- e 2kT dvx Eq. 87
2πkT
How initial velocities are The initial velocities are generated from the Gaussian distribution
generated of vx, vy, and vz. The Gaussian distribution is generated from a ran-
dom number generator and a random number seed.
∑
p i2 Nf k B T
------- = 〈K 〉 = --------------- Eq. 88
2m 2
i
The left side of Eq. 88 is also called the average kinetic energy of
the system, Nf is the number of degrees of freedom, and T is the
thermodynamic temperature. In an unrestricted system with N
atoms, Nf is 3N because each atom has three velocity components
(i.e., vx, vy, and vz).
Instantaneous kinetic It is convenient to define an instantaneous kinetic temperature
temperature function:
2K
T instan = ----------- Eq. 89
Nf k B
The thermodynamic tem- The average of the instantaneous temperature Tinstan is the ther-
perature modynamic temperature T.
Temperature is calculated from the total kinetic energy and the
total number of degrees of freedom. For a nonperiodic system:
Temperature in nonperi- N
odic systems… ( 3N – 6 )k B T
∑
m i v i2
------------------------------- = ------------ Eq. 90
2 2
i=1
N
( 3N – 3 )k B T
∑
m i v i2
------------------------------- = ------------ Eq. 91
2 2
i=1
Andersen method
simulation engine
method
CHARMm Discover OFF
Velocity scalinga
√ √ √
Berendsen temperature bathb √ √ √
Nosé √
Nosé–Hooverc √d √
Andersen √4
aTemperature scaling is not generally used to control temperature during a
simulation, but to quickly change the simulated temperature to the desired
value. It does not produce the correct statistical ensemble.
bReferred to as T_DAMPING in Cerius2•Dynamics Simulation.
c
Referred to as Nosé in the Cerius2•Discover and Insight•Discover_3 mod-
ules and Hoover in Cerius2•Dynamics Simulation.
dCDiscover only, not in FDiscover.
Choosing the tempera- To access the controls used for specifying the temperature-control
ture-control method(s) method:
♦ In Cerius2, go to the DYNAMICS SIMULATION card on the
OFF METHODS deck of cards. Click the Run card menu item
to access the Dynamics Simulation control panel. You can set
the target temperature for velocity scaling with the Required
Temperature entry box. The Preferences… buttons for each
statistical ensemble and type of dynamics simulation give
access to additional temperature-control methods and parame-
ters.
♦ In Cerius2•Discover, click the Run menu item on the DIS-
COVER card to access the Run Discover control panel. Set the
Task popup to Dynamics and click the More… pushbutton to
the right of the Task popup. Set the Ensemble popup in the Dis-
cover Dynamics control panel to NVT or NPT and select the
Thermostat. Other controls depend on which thermostat you
choose.
Important
Direct velocity scaling can not be used to generate realistic
thermodynamic ensembles, since it suppresses the natural
fluctuations of a system.
Implementation In Discover, the velocities of all atoms are scaled uniformly as fol-
lows:
v new 2 T target
----------
- = ---------------- Eq. 92
v old T system
2
---------- ( T – T avg ) + 1 Eq. 93
T inst r
1/2
∆t T – T 0
λ = 1 – ----- --------------- Eq. 94
τ T
dq i pi
= ----- Eq. 96
dt mi
dp i dφ
= – – ζp i Eq. 97
dt d qi
∑
p i2
------ – gkB T
dζ mi
= ------------------------------------ Eq. 98
dt Q
Andersen method
One version of the Andersen method of temperature control
involves randomizing the velocities of all atoms at a predefined
“collision frequency”. (The other version involves choosing one
atom at each timestep and changing its velocity according to the
Boltzmann distribution.)
The CDiscover program implements the first version. The pre-
defined frequency is proportional to N 2/3, where N is the number
of atoms in the system. Although this frequency is calculated by
the program, you can change it.
What are pressure and Pressure is another basic thermodynamic variable that defines the
stress? state of the system. It is a familiar concept, defined as the force per
unit area. Standard atmospheric pressure is 1.013 bar, where 1 bar
= 105 Pa. A single number for the pressure implies that pressure is
P P xy P xz
xx
P = P yx P yy P yz Eq. 99
P P zy P zz
zx
Each element of the tensor is the force that acts on the surface of an
infinitesimal cubic volume that has edges parallel to the x, y, and z
axes. The first subscript refers to the direction of the normal to the
plane on which the force acts, and the second subscript refers to
the direction of the force.
In an isotropic situation, where forces are the same in all directions
and there is no viscous force, the pressure tensor is diagonal. With
the same diagonal elements, the tensor can be written as:
1 0 0
P = p 0 1 0 Eq. 100
0 0 1
and 1 GPa = 109 N m-2. Hence, 1 GPa = 104 bar. Pressure is usually
expressed in bars, but in materials science, stress is often expressed
in terms of GPa.
In the CDiscover program, constant-stress dynamics has GPa as
the default unit. Since the FDiscover program is geared towards
controlling pressure, the unit used is bar. In the Cerius2•Dynamics
Simulation module, GPa are the only units used for pressure and
stress.
Although pressure and stress are defined with the same physical
quantities, they have opposite sign conventions. Positive pressure
implies a compressive force pushing the system inward, but posi-
tive stress means a force acting outward to expand the system.
∑r ⋅ f
1
W = --- i i Eq. 102
2
i=1
Volume (and pressure) is Note that pressure is defined only when the system is placed in a
known only for periodic container having a definite volume. In a computer simulation, the
models unit cell under periodic boundary conditions is viewed as the con-
tainer. Volume, pressure, and density can be calculated only when
the model is recognized as periodic.
Nk b T 2 W
P = -------------- + --- ------ Eq. 103
V 3V
2
T = ------------- K Eq. 104
3Nk b
2
P = ------- ( K + W ) Eq. 105
3V
Instantaneous pressure As mentioned above, pressure is a tensor and its components can
tensor also be expressed in tensorial form. Eq. 101 can be recast in the
form of:
N N
∑m v v + ∑r f
1 T T
P = --- i i i i i Eq. 106
V
In detail, the two terms on the right-hand side of the equation are:
∑m v v ∑m v v ∑m v
i ix ix i ix iy i ix v iz
N i i i
∑m v v
T
i i i = ∑m v v ∑m v v ∑m v
i iy ix i iy iy i iy v iz Eq. 107
i=1 i i i
∑m v v ∑m v v ∑m v v
i iz ix i iz iy i iz iz
∑r f ∑r f ∑r
ix ix ix iy ix f iz
N i i i
∑r f
T
i i = ∑r f ∑r f ∑r
iy ix iy iy iy f iz Eq. 108
i=1 i i i
∑r f ∑r f ∑r f
iz ix iz iy iz iz
Instantaneous hydrostatic where rix, vix, and f ix indicate the x components of the position,
pressure velocity, and force vectors of the ith atom, respectively.
From the definition of the instantaneous pressure tensor, the
instantaneous hydrostatic pressure is calculated as 1/3 the trace of
the pressure tensor (Pxx + Pyy + Pzz).
Forces on the image When periodic boundary conditions are used, atoms in the unit
atoms cell interact not only with the other atoms in the unit cell but also
with their translated images. Forces on the images in the virial W
must be included correctly. If the interaction is pairwise, using
Newton’s third law, W can be written as:
∑r f
1
W = --- ij ij Eq. 109
2
>
instead of:
∑r f
1
W = --- i i Eq. 110
2
Berendsen et al. (1984) use the rij ⋅ fij formalism by evaluating the
virial and the kinetic energy tensor based on the centers of mass,
which is valid because the internal contribution to the virial is can-
celed (on the average) by the internal kinetic energy. Because of the
way forces are evaluated, rescaling of coordinates is also done on
the basis of the centers of mass of the models.
How coordinates are The Discover program, however, calculates pressure on an atomic
scaled in response to pres- basis and performs atomic scaling. The major advantage of using
sure changes atomic scaling of the coordinates is that atom overlapping can be
avoided. Such overlap can occur if centers of mass are moved
simulation engine
method
CHARMm Discover OFF
Berendsen pressure “bath” √ √
Andersen √a √
Parrinello–Rahman √1 √
aCDiscover
only, not in FDiscover.
Important
With the Berendsen and Andersen methods the volume can
change, but there is no change in the shape of the cell; thus only
the pressure is controlled. With the Parrinello–Rahman method,
the cell’s shape can change, and therefore both pressure and
stress can be controlled.
Choosing the pressure- To access the controls used for specifying the pressure- and stress-
and/or stress-control control methods:
method(s)
♦ The Cerius2•Dynamics Simulation module automatically uses
the Parrinello–Rahman method to control stress and the Ander-
sen method to control pressure.
♦ In the Cerius2•Discover and Insight•Discover_3 modules, the
Parrinello–Rahman method is the default for pressure (and
stress) control. If you really want to change it, you can write out
the command input file, edit the BTCL dynamics command
statement with a text editor, and then use that file for your run.
Alternatively (for Insight•Discover_3), select the Language_
Control/Command_Comment command. Set the Comment
Type to Command. Enter pressure_control_method =
Andersen_cp or pressure_control_method = Berendsen_pc in
the Command/Comment entry box and select Execute. Be sure
that you insert this stage at the correct point in your command
input file.
♦ The Insight•Discover and QUANTA•CHARMm modules
always uses the Berendsen pressure-control method.
1/3
∆t
µ = 1 + -------- γ [ P – P 0 ] Eq. 111
τ
N N N
p ( Ω – Ω 0 ) + Ω 0 Tr ( S – p )ε Eq. 113
Langevin dynamics
Stochastic boundary dynamics
Multibody order-N dynamics
simulation engine
method
CHARMm Discover OFF
Quenched dynamics √a
√
Simulated annealing √b √1 √
Consensus dynamics √c
Impulse dynamics √d √
Langevin dynamics √
Stochastic boundary dynamics √
a
Available through Insight•Discover_3 module for CDiscover, via DSL only for
FDiscover; not yet available in Cerius2•Discover.
b
Truncated (only one T-to-0 K half-cycle), and referred to as “quenched
dynamics” in the CHARMm documentation.
cAvailable in standalone mode only.
d
Available in standalone mode of CDiscover only.
Choosing the type of To access the controls used for specifying types of dynamics simu-
dynamics lations:
♦ In Cerius2, go to the DYNAMICS SIMULATION card on the
OFF METHODS deck of cards. Click the Run card menu item
to access the Dynamics Simulation control panel. Check the
check box next to the desired type of simulation. You can access
additional controls relevant to each type by clicking the Prefer-
ences… button to its right.
♦ To set up complicated dynamics runs with the Insight•
Discover_3 module, you need to set up several stages of mini-
mization (if desired) and dynamics, using the Calculate/Mini-
mize and Calculate/Dynamics commands. You probably also
need to write and read appropriate files at various stages of the
run with the Language_Control/File_Control command. In
Quenched dynamics
How it works In quenched dynamics, periods of dynamics are followed by a
quench period in which the structure is minimized. You can spec-
ify the simulation time between quenches and the number of min-
imization steps. The quenched structure can then be written to a
trajectory file (Dynamics trajectories), and dynamics continues with
the prequenched structure.
Uses Quenched dynamics is a way to search conformational space for
low-energy structures.
Simulated annealing
How it works In simulated annealing, the temperature is altered in time incre-
ments from an initial temperature to a final temperature and back
again. This cycle can be repeated. The temperature is changed by
adjusting the kinetic energy of the structure (by rescaling the
velocities of the atoms).
Simulated annealing can be combined with quenched dynamics.
That is, at the end of each temperature cycle, the lowest-energy
structure of that cycle can be minimized and saved in a trajectory
file (Dynamics trajectories). Annealing continues using the last
structure and velocities from the previous cycle.
Tip
Use the quartic form of the nonbond term for simulated
annealing studies in which the initial coordinates are unknown.
These simulations can involve atoms moving through other
atoms and for this it is essential that the nonbond term not go to
infinity.
Consensus dynamics
How it works Consensus dynamics can be thought of as an extension of the teth-
ering restraint technique (Template forcing, tethering, quartic droplet
restraints, and consensus conformations). In tethering, a model sys-
tem serves as a fixed template. The “moving” system, driven by
molecular mechanics or dynamics, is then forced to conform to the
template by applying restraints.
In contrast, the consensus technique allows the “template” to
respond to changes in the “moving” system, by treating all the
models as “moving templates”. The net result is that both models
change so that their structures become similar. Consensus dynam-
ics can be applied to more than two models simultaneously.
Uses Consensus restraints have several uses. One example is the deter-
mination of structural similarities among a set of homologous
compounds—perhaps several similar compounds that bind to a
particular receptor. If you hypothesize that an apparently homolo-
gous region of the compounds is responsible for the binding, then
you would want to find a configuration for this region that is com-
patible with relatively low-energy conformations for all the com-
pounds. By applying consensus restraints to the homologous
region of each compound, you can use dynamics followed by min-
imization to find a likely binding configuration.
Impulse dynamics
How it works Impulse dynamics allows you to assign initial directional veloci-
ties to selected atoms before carrying out dynamics.
Impulse dynamics can be used only with constant-energy, con-
stant-volume dynamics (NVE ensemble) and cannot be combined
with simulated annealing (Simulated annealing).
Uses You can use impulse dynamics to push interacting molecules over
energy barriers before allowing the structure to relax.
Langevin dynamics
How it works The Langevin dynamics method (McCammon et al. 1976, Levy et
al. 1979) approximates a full molecular dynamics simulation of a
system by eliminating unimportant or uninteresting degrees of
freedom. The effects of the eliminated degrees of freedom are sim-
ulated by mean and stochastic forces.
Friction coefficients must be assigned to selected atoms before
starting the dynamics run. Langevin dynamics includes a con-
stant-temperature bath.
Uses For example, instead of simulating hundreds of solvent molecules
surrounding the solute molecules, the solvent can be ideally repre-
sented as a viscous fluid described in terms of dissipative and fluc-
tuative equations.
Setting constraints during To access the controls used for setting up SHAKE or RATTLE
dynamics dynamics:
♦ In the Cerius2•Discover module, select the Run menu item in
the DISCOVER card to open the Run Discover control panel.
In this control panel, set the Task popup to Dynamics and click
the More… pushbutton to the right of the Task popup to open
the Discover Dynamics control panel. In this panel, check the
Rattle check box and click the More… pushbutton to its right
to open the Rattle control panel. Use the latter to specify
whether bonds and/or angles should be constrained.
♦ In the Insight•Discover_3 module, select the Calculate/
Dynamics command, toggle More on, and then toggle Rattle
on.
Note
For full access to the RATTLE functionality, you need to use
BTCL statements. You can write out a command input file from
Cerius2 or Insight, edit the BTCL rattle command statement(s)
with a text editor, and then use that file for your run.
Alternatively (in Insight), select the Language_Control/
Command_Comment command. Set the Comment Type to
Command. Enter the desired rattle command statement(s) in
the Command/Comment entry box and select Execute.
Tip
We do not recommend that angle constraints be used even
though this functionality is available. However, if angle
constraints have to be used, you should use a larger tolerance
than with bonds.
Tip
To maintain a high degree of accuracy during the dynamics
simulation, as well as to provide a larger integration time step,
it is best to apply SHAKE only to bonds containing hydrogens.
Effect on timestep A twofold increase in the time step (to 0.001 ps) is enabled.
Note
For the time being, RATTLE cannot be used with constant-
pressure dynamics, since that involves calculating the pressure
on a molecule basis, which is not currently available.
Dynamics in fixed-geome- Another major use of RATTLE is to enable the use of a fixed-geom-
try water etry water model. With RATTLE, you can use the SPC, TIP3P, or
current water models. The initial configurations of the water mol-
ecules are set to the equilibrium geometry of the SPC or TIP3P
model or to the current geometry of water in your model.
Dynamics trajectories
What are trajectories? The results of dynamics simulations can be saved in trajectory
files, which are essentially a series of snapshots of the simulation
taken at regular intervals. Trajectories can include data such as
model structure, minimized-model structure (in quenched
dynamics, see Quenched dynamics), temperature, energies, volume,
pressure, cell parameters, and stress.
Uses Trajectory files can be used for analysis of the results and also for
continuing an interrupted dynamics simulation.
You can use trajectory files for computing the average structure
and for analyzing fluctuations in geometric parameters, thermo-
dynamic properties, and time-dependent processes. The time
series can be evaluated for global properties such as the radius of
gyration and the number density of the model. Examples of exper-
imental quantities that can be calculated using correlation func-
tions are frictional coefficients, IR line widths, fluorescence
depolarization rates, spectral densities (the Fourier transform of
the correlation function), and NMR relaxation times.
Animations You can also animate trajectories, to view how the model behaved
during a dynamics run.
Typically, the displayed model’s conformation is updated during
a run so you can monitor progress visually. The frequency with
which the display is updated can affect the time needed to perform
a dynamics simulation, especially with large models.
With the Cerius2•Dynamics Simulation module, some informa-
tion also can be displayed in the form of graphs that are updated
as the run proceeds.
Prerequisites One of the most important steps in any simulation is properly pre-
paring the system to be simulated. Calculations on the fastest com-
puter running the most efficient dynamics algorithm may be
worthless if the hydrogen is put on the wrong nitrogen or an
important water molecule is omitted.
Unfortunately, it is impossible to provide a single recipe for a suc-
cessful model—too much depends on the objectives and expecta-
tions of each calculation. Are conformational changes that are far
removed in conformational space from the area being focused on
expected or interesting? What is the hypothesis being tested? The
effects of specific dynamics variables, as well as tethering, fixing,
energy cutoffs, etc., on the results can be answered only by con-
trolled preliminary experiments.
One empirical way to find out how long is long enough for a
dynamics simulation is to monitor the change in the desired quan-
tities over time.
The length of a trajectory needed to calculate a property depends
on the time variation of the property under consideration. If the
property is a slowly varying function, the dynamics integration
should be extended to cover several periods.
Characteristic durations for common events in real molecules are
listed in Table 23.
Verifying the run instruc- 6. Review what you have requested for the run:
tions
Since dynamics simulations are often quite complex and time
consuming, you should review your run specifications before
starting the simulation.
♦ In the Cerius2•Discover module, select the Run menu item in
the DISCOVER card to open the Run Discover control panel.
In this control panel, click the Input… pushbutton to open the
Discover Input File control panel. Click the Save Strategy to
.inp File action button.
♦ In the Insight•Discover_3 module, select the Setup/List com-
mand, set List Options to Input_File, and select Execute. The
command input file is listed in the textport. Then you can read
the input file by using any text editor, issuing the UNIX more
command, or clicking the Edit .inp File action button.
♦ In the Insight•Discover module, select the Parameters/Dynam-
ics or the Run/Run command. Toggle the List option on and
select Execute to view the parameters you have set so far.
To view the complete command input file, select the Run/Run
command. Set the controls as desired, being sure that Run_
Dynamics is on and Computation Mode is set to Command
File, and select Execute. (Run_Minimization can be on or off,
depending on whether you want to specify that minimization
be performed before the dynamics equilibration stage.) Read
the input file with any text editor or the UNIX more command.
Specific information For specific information on setting up and running dynamics with
the various MSI simulation engines, and on analyzing the results,
please see the relevant documentation (see Available documenta-
tion).
Files and precautions The trajectory and other input file(s) that are required depend on
what simulation engine is being used, and the exact procedure
depends on whether you a continuing a run without a break from
the last conformation of an immediately preceding run, restarting
an interrupted run from the last conformation, or using an inter-
mediate point of an earlier run as the basis for a new simulation.
If you changed the model’s conformation (for example, by minimi-
zation) since your previous dynamics simulation ended, you need
to reassign the initial (random) velocities, since the old velocities
do not apply to the new coordinates. The Insight•Discover_3 and
Cerius2•Dynamics Simulation modules can detect this situation
and reinitialize velocities automatically.
You may need to analyze the data from a dynamics run before
doing a restart from other than its final conformation. You may, for
example, want to find and use the lowest-energy conformer as the
starting point for a new simulation or may want to restart a run
with a particular set of velocities.
Please see the relevant specific documentation (Available documen-
tation).
Restarting a dynamics Briefly, the general procedure with each simulation engine is:
simulation
♦ In the Cerius2•Dynamics Simulation module, specify the tra-
jectory file with the Dynamics Trajectory Input control panel,
which is accessed by selecting the Trajectory/Input item from
the DYNAMICS SIMULATION card. Use this control panel to
restart an interrupted run at its final conformation, to specify
the conformation number at which to begin a new run, and to
specify the type of data to use from the previous run.
To restart the simulation at the last step of an immediately pre-
ceding run, click the RUN DYNAMICS button in the Dynam-
ics Simulation control panel.
To start a new simulation from the end or some point before the
end of a previous run, specify a new dynamics method, algo-
rithm, output, etc., if desired (see Purpose of the run). Then click
the RUN DYNAMICS button.
To re-randomize the atomic velocities before starting a new run,
click the Reset button in the Dynamics Simulation control panel
before clicking the RUN DYNAMICS button.
Who should read this Forcefield-based calculation of relative or absolute free energy
chapter should be considered an “expert” application. We recommend
using the FDiscover program for relative and absolute free energy
calculations. Although it is possible to run relative free energy cal-
culations with CHARMm, that program is slower and less flexible.
This chapter explains Relative free energy—theory and implementation
Absolute free energy
A = – k B T ln Q Eq. 114
If Q1 and Q2 are the partition functions for States 1 and 2, the dif-
ference in free energy between these states is:
Q2
∆A = A 2 – A 1 = – k B T ln ------ Eq. 115
Q1
exp [ – E 1 /k B T ]
P 1 = ----------------------------------- Eq. 117
Q1
Q2
------ = 〈 exp [ – ∆E/k B T ]〉 1 Eq. 118
Q1
This approach is accurate only when the energy of the initial and
final states differs by a small amount, on the order of 2 kBT. Larger
energy differences than this lead to such small values for the expo-
nential term that the statistical uncertainty overwhelms the
observable. For small changes, this method is very attractive
because it calculates the complete free energy difference in one cal-
culation.
To calculate free energy differences larger than 2 kBT, several
sequential runs are performed, each computing the free energy
change over a subinterval. Errors introduced by failure to con-
verge at each step are propagated—each successive calculation
adds its contribution to the previously accumulated total.
FDTI Thermodynamic integration of the relative free energy assumes
that the free energy change can be expressed as an integral:
∫ -------------
δA(λ)
∆A = dλ
δλ
0
k
ln 〈 exp [ – ( E(λi ) – E ( λ i ± δλ ) )/k B T ]〉i
∆A = – k B T
∑ --------------------------------------------------------------------------------------------- ∆λ i Eq. 121
δλ
i=1
2
E(b ;λ) = λK A
+ ( 1 – λ )K
B
b–
A
[ λb 0 + (1 –
B
λ )b 0 ] Eq. 123
∆A 1
∆A 3 ↓ ↓ ∆A 4
∆A 2
CH 3 OH ( g ) → CH3 OH ( aq )
∆A 4 – ∆A 3 = ∆A 2 – ∆A 1 Eq. 124
1.1
exp (–∆E/kT)
1.0
0.9 λ = 0.056
λ = 0.44
λ = 0.94
0.8
10 12 14 16 18 20
Time (ps)
Figure 32. The ensemble-averaged quantity from Eq. 120 plotted vs.
time for three values of λ
Each point plotted is actually an average of 10 points sampled over 100 fs.
Column 5 of the .tot file [exp –(∆E ⁄ kT)] for the first, third, and last
λ points for the methanol-to-ethane gas phase calculation. Note
that there is a slight upward drift in the curve for the first λ point,
although the others seem to have converged.
∑ 2m
1 1
H Ideal Solid = --------
- --------- ( p 2
xi + p y2 + p z2 )
h 3N i i i
i
Eq. 125
N
∑
0 2 0 2 0 2
+ Ki ( xi – xi ) d ( yi – yi ) + ( zi – z i )
N
3⁄2
2m i πk B T 2
Q =
∏ --------- -------------
Ki h
Eq. 126
i=1
Returning to Eq. 114, the free energy of the model ideal solid can
be written as:
N
2
2m i πk B T
∑
3
A ideal solid = – --- k B T ln --------- --------------- Eq. 127
2 Ki h
i=1
∫ -------------
∂A ( λ )
A1 – A 0 = dλ Eq. 128
∂λ
0
Substituting the equation for the free energy (Eq. 114) into Eq. 128,
we can write the difference in free energy as a function of the par-
tition function Q(λ):
1 1
∂[ – k B T ln Q(λ) ]
∫ ∫
1 ∂Q(λ)
A1 – A0 = ---------------------------------------- dλ = – k B T ----------- -------------- dλ Eq. 129
∂λ Q(λ) ∂λ
0 0
∫ -------------------------
∂H(p, r, λ)
A1 – A0 = dλ Eq. 130
∂λ
0
Here, K(p) is the kinetic energy (because the two states are com-
pletely defined by their respective potential energy functions, the
kinetic energy does not have to be coupled to λ), V0 is the normal
potential energy function (including bonds, angles, torsions, etc.),
and VH is a harmonic oscillator site potential given by:
∑ K (r – r )
0 2
VH = i i i Eq. 132
Parameterization of the where Ki is the ith atom’s spring constant, ri is the ith atom’s instan-
Hamiltonian taneous coordinate, and ri0 the reference lattice of the noninteract-
ing atoms (often referred to as an Einstein solid). This choice of
parameterization is motivated by the template-forcing concept in
the FDiscover program and by previous free energy evaluations
(Hoover and Ree 1967). In Eq. 131, λ is greater than 0 and less than
1, and describes an energy–space path between a system described
by an unadulterated molecular forcefield (λ = 0) and one repre-
sented by independent harmonic oscillators (λ = 1).
Eq. 132 is thus the reference system for which an absolute free
energy can be directly calculated. The potential VH restricts the
exploration of phase space to a region defined by atomic mean-
squared displacements relative to the Einstein solid. Conse-
quently, the choice of both the reference state and spring constants,
in general, affects the calculated free energies. For most cases, the
energy-minimized coordinates of a mechanically stable structure
are used for the reference Einstein solid. Using Eq. 127 for the free
energy of the Einstein solid A1 and Eqs. 130 through 132, the abso-
lute free energy of the real state is:
Absolute free energy of 1
∫ ∂ λ[ K(p) + ( 1 – λ )V + λH ] dλ
the real state ∂
A0 = A1 – 0 H
0
1
= A1 +
∫ V –V
0 H dλ
Eq. 133
Computational consider- The simple form of Eq. 133 makes evaluating its ensemble average
ations and precautions straightforward. A comprehensive dynamics trajectory for a given
value of λ represents an ensemble of structures for that λ. By com-
puting and averaging the values of (V0 – VH) for each structure in
this ensemble, the integrand can be numerically estimated for any
given value of λ. By performing several such calculations for many
Example: Fentanyl
This example presents a calculation of the free energies of various
conformational states of fentanyl (Figure 33). Previous studies of
C1
N3 C5
C2 C4
φ1 = C1–C2–N3–C4
φ2 = C2–N3–C4–C5
Figure 33. Definitions of φ1 and φ2 for fentanyl
100 a b
c
φ2 0
1
0 24 8 2
-100
6 8 64
10
-100 0 100
φ1
Figure 34. Two-Dimensional energy map of fentanyl as a function of the
two dihedral angles defined in Figure 33
Locations a and b correspond to the two unique minima, and c is at a transition
state.
The reference state has two roles in the free energy calculation. A
trivial contribution is the free energy it contributes as an ideal
solid. This contribution is trivial because it does not depend on the
conformation of the reference structure. It depends only on the
masses of its atoms and the spring constants constraining each
atom to the lattice (see Eq. 127).
The nontrivial role is that it determines which part of configura-
tional space is sampled during dynamics. In this example, the free
energies of states a, b, and c (Figure 34) of fentanyl are compared.
The reference states for a and b correspond to completely mini-
mized structures at these points. Point c in Figure 34 represents the
100
φ2 0
1
0 24 8 2
-100 6 8 64
10
-100 0 100
φ1
Figure 35. Time history of the dihedral angles φ1 and φ2 superimposed on
the 2D energy map of Figure 34
Two trajectories are plotted, one for a minimum corresponding to state a in
Figure 34, the other for the transition state (c). Note that only a small fraction of
the conformational space of the model needs to be sampled to estimate the
free energy of a conformer. Each trajectory corresponds to the first λ value, i.e.,
when the potential function is most like the standard potential.
One important property of the .cli file is that, if the file exists when
the free energy calculation begins (for example, from an earlier or
different run), the reference state is read from the file regardless of
any prior tethered atom list generated. This does not mean that if
a .cli file is provided, a tethered atom list command is not needed.
Rather, if the .cli file is present, no matter what conformation is
used for the tethered atom list command, the actual reference
structure used is that in the .cli file. Be aware then, when doing
new free energy calculations requiring different reference states
that any existing .cli files that would override the internally gener-
ated reference state must be removed.
The magnitude of the spring constants in Eq. 132 indirectly affects
the free energy calculated by controlling the volume of phase
space being sampled during dynamics. Large spring constants
bias the sampling to the immediate neighborhood of the reference
structure. Smaller values allow the model to sample more space.
The spring constants also affect the error associated with a calcu-
lation. Ensembles that contain structures far from the reference
state make greater contributions to the free energy, by virtue of the
greater fluctuations in (V0 – VH) for this ensemble.
The FDiscover program provides two methods for assigning
spring constants:
1. All atoms are assigned the same value. You may want to assign
large Ki values when you are studying a mechanically unstable
state, to constrain dynamics to phase space near the reference
structure. In the FDiscover standalone version this choice is
specified by including the keyword assigning in the free
energy command along with the specification of a spring con-
stant. In the Insight environment, the force constant is con-
trolled by changing the Spring Constant parameter in the
Parameters/Absolute command.
2. Spring constants can be estimated from the definition of mean-
squared displacements under a harmonic potential. In this case,
the following expression is used:
kB T
K i = ----------------- Eq. 134
∆x 2 0
and the default is for each atom to receive a unique value of Ki.
Analysis of results
Available output Although a free energy calculation is done as a single FDiscover
run, the calculation actually consists of several independent cycles
of dynamics equilibration (initialize dynamics) and data collec-
tion (resume dynamics)—as many cycles as λ intervals. The
1 0.8 1.0
∫ dλ V – V
0 H =
∫ dλ V – V + ∫ dλ V – V
0 H 0 H Eq. 135
0 0 0.8
Absolute free energy files The .cli file contains the free energy comparison list, i.e., the tem-
and output plate coordinates prevalent during tethering. This file can be used
as input for further simulations with the same template coordi-
nates, by specifying file filename with the calculate command in
the standalone version of the FDiscover program.
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Catlow, C. R. A.; Norgett, M. J. “Lattice structure and stability of
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Dauber–Osguthorpe, P.; Roberts, V. A.; Osguthorpe, D. J.; Wolff, J.;
Genest, M.; Hagler, A. T. “Structure and energetics of ligand
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prim, a drug–receptor system”, Proteins: Structure, Function
and Genetics, 4, 31–47 (1988).
Deem, M. W.; Newsam, J. M.; Sinha, S. K.. “The h = 0 term in Cou-
lomb sums by the Ewald transformation”, J. Phys. Chem., 94,
8356–8359 (1990).
Demontis, P.; Yashonath, S.; Klein, M. L. “Localization and mobil-
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This appendix explains This appendix includes tables of atom types for these forcefields:
Original AMBER. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . here
Homans’ AMBER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . here
CFF91 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . here
CHARMm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . here
COMPASS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . here
CVFF. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . here
CVFF_aug . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . here
ESFF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . here
PCFF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . here
force-
name illustrated form of the term fielda
quadratic AMBER,
bond- k ( r – r0 ) 2 CHARMm,
stretching UFF
quartic CFF
bond- k2 ( r – r0 )2 + k3 ( r – r0 ) 3 + k4 ( r – r 0 ) 4
stretching
Morse bond- 0 2 CVFF, ESFF
stretching ( –α ( r b – rb ) )
k 1–e
quadratic AMBER,
angle- k ( θ – θ0 )2 CHARMm,
bending CVFF
quartic CFF
angle- k2 ( θ – θ0 )2 + k3 ( θ – θ0 ) 3 + k4 ( θ – θ 0 ) 4
bending
cosine ESFF, UFF
angle- various
bending
single-cosine AMBER,
torsion k ( 1 + cos ( nφ – φ 0 ) ) or similar CHARMm,
CVFF
three-term k 1 [ 1 – cos ( φ – φ 01 ) ] + k 2 [ 1 – cos ( 2φ – φ 02 ) ] CFF
cosine tor-
sion + k 3 [ 1 – cos ( 3φ – φ 03 ) ]
cosine-Fou- UFF
rier torsion
k ( 1 ± cos nφ )
sin–cos tor- ESFF
sin2 θ 1 sin2 θ 2 sinn θ 1 sin2 θ 2
sion - cos [ nφ ]
k φ -------------------------------- + sign -------------------------------
sin2 θ 1 sin2 θ 2
0 0 0
sinn θ 1 sinn θ 2
0
force-
name illustrated form of the term fielda
improper AMBER,
cosine out- k [ 1 + cos ( nχ – χ 0 ) ] or similar CVFF, UFF
of-plane 3 4
improper CHARMm
quadratic
k ( χ – χ0 )2
out-of- 2
plane
improper CVFF
square out- 1
of-plane, kχ 2
imprope
Wilson (or CFF, ESFF,
umbrella) kχ 2 UFF
out-of- UFF
plane
k ( cos χ – cos χ 0 ) 2
pyrimid- none
height out-
of-plane
not used
electrostatic AMBER,
q i qj CFF,
--------- or similar CHARMm,
εr ij CVFF, ESFF,
UFF
force-
name illustrated form of the term fielda
quadratic CFF,
bond– CVFFb
bond k ( r – r 0 ) ( r′ – r′ 0 )
k ( θ – θ 0 ) ( θ′ – θ′ 0 )
center CFF
bond–tor-
sion ( b′ – b′0 ) [ k 1 cos φ + k 2 cos 2φ + k 3 cos 3φ ]
angle–torsion CFF
force-
name illustrated form of the term fielda
angle– CFF, CVFF
angle–tor-
sion k cos φ ( θ – θ 0 ) ( θ′ – θ′0 )
improper CVFF
out-of-
plane–-out-
of-plane,
improper k [ 1 – cos 2χ ] 1 / 2 [ 1 – cos 2χ′ ] 1 / 2
aMajor
forcefields, for the purposes of this table, are AMBER, CFF, CHARMm, CVFF, ESFF, UFF.
b
AMBER, CHARMm, ESFF, and UFF contain no cross terms.
gener- atom
al class typea description
hydrogen types
H amide or imino hydrogen
HC explicit hydrogen attached to carbon
HO hydrogen on hydroxyl oxygen
HS hydrogen attached to sulfur
HW hydrogen in water
H2 amino hydrogen in NH2
H3 hydrogen of lysine or arginine (positively charged)
all-atom carbon typesb
gener- atom
al class typea description
2
C sp carbonyl carbon and aromatic carbon with hydroxyl substit-
uent in tyrosine
CA sp2 aromatic carbon in 6-membered ring with 1 substituent
CB sp2 aromatic carbon at junction between 5- and 6-membered
rings
CC sp2 aromatic carbon in 5-membered ring with 1 substituent and
next to a nitrogen
CK sp2 aromatic carbon in 5-membered ring between 2 nitrogens
and bonded to 1 hydrogen (in purine)
CM sp2 same as CJ but one substituent
CN sp2 aromatic junction carbon in between 5- and 6-membered
rings
CQ sp2 carbon in 6-membered ring of purine between 2 NC nitro-
gens and bonded to 1 hydrogen
CR sp2 aromatic carbon in 5-membered ring between 2 nitrogens
and bonded to 1 H (in his)
CT sp3 carbon with 4 explicit substituents
CV sp2 aromatic carbon in 5-membered ring bonded to 1 N and
bonded to an explicit hydrogen
CW sp2 aromatic carbon in 5-membered ring bonded to 1 N–H and
bonded to an explicit hydrogen
C* sp2 aromatic carbon in 5-membered ring with 1 substituent
united carbon typesc
CD sp2 aromatic carbon in 6-membered ring with 1 hydrogen
CE sp2 aromatic carbon in 5-membered ring between 2 nitrogens
with 1 hydrogen (in purines)
CF sp2 aromatic carbon in 5-membered ring next to a nitrogen with-
out a hydrogen
CG sp2 aromatic carbon in 5-membered ring next to an N–H
CH sp3 carbon with 1 hydrogen
CI sp2 carbon in 6-membered ring of purines between 2 NC nitro-
gens
CJ sp2 carbon in pyrimidine at positions 5 or 6 (more pure double
bond than aromatic with 1 hydrogen)
CP sp2 aromatic carbon in 5-membered ring between 2 nitrogens
with one hydrogen (in his)
C2 sp3 carbon with 2 hydrogens
C3 sp3 carbon with 3 hydrogens
gener- atom
al class typea description
nitrogen types
N sp2 nitrogen in amide group
NA sp2 nitrogen in 5-membered ring with hydrogen attached
NB sp2 nitrogen in 5-membered ring with lone pairs
NC sp2 nitrogen in 6-membered ring with lone pairs
NT sp3 nitrogen with 3 substituents
N2 sp2 nitrogen in base NH2 group or arginine NH2
N3 sp3 nitrogen with 4 substituents
N* sp2 nitrogen in purine or pyrimidine with alkyl group attached
oxygen types
O carbonyl oxygen
OH alcohol oxygen
OS ether or ester oxygen
OW water oxygen
O2 carboxyl or phosphate nonbonded oxygen
sulfur types
S sulfur in disulfide linkage or methionine
SH sulfur in cystine
phosphorus
P phosphorus in phosphate group
ion types
CU copper ion (Cu+2)
CØ calcium ion (Ca+2)
I iodine ion (I–)
IM chlorine ion (Cl–)
MG magnesium ion (Mg+2)
QC cesium ion (Cs+)
QK potassium ion (K+)
QL lithium ion (Li+)
QN sodium ion (Na+)
QR rubidium ion (Rb+)
gener- atom
al class typea description
other
LP lone pair
a
From Weiner et al. (1984) and Weiner et al. (1986).
bNon-hydrogen-containing carbons.
c
United-atom carbons with implicit inclusion of hydrogens.
atom
general class type description
hydrogen types
dw deuterium in heavy water (equiv. to h*)
h hydrogen bonded to C or S
hc hydrogen bonded to C (equiv. to h)
hi hydrogen in charged imidazole ring
hn hydrogen bonded to N (equiv. to h*)
ho hydrogen bonded to O (equiv. to h*)
hp hydrogen bonded to P (equiv. to h)
hs hydrogen bonded to S (equiv. to h)
hw hydrogen in water (equiv. to h*)
h* polar hydrogen bonded to N or O
h+ charged hydrogen (in cation)
carbon types
c generic sp3 carbon
ca general amino acid alpha carbon (sp3) (equiv. to c)
cg sp3 alpha carbon in glycine (equiv. to c)
ci sp2 aromatic carbon in charged imidazole ring (his+)
(equiv. to cp)
co sp3 carbon in acetal (equiv. to c)
coh sp3 carbon in acetal with hydrogen (equiv. to c)
cp sp2 aromatic carbon
cr carbon in guanidinium group (HN=C(NH2)2) (arg)
cs sp2 carbon in 5-membered ring next to S (equiv. to cp)
ct sp carbon involved in triple bond
c1 sp3 carbon bonded to 1 H, 3 heavy atoms (equiv. to c)
c2 sp3 carbon bonded to 2 H’s, 2 heavy atoms (equiv. to
c)
c3 sp3 carbon in methyl (CH3) group (equiv. to c)
c5 sp2 aromatic carbon in 5-membered ring (equiv. to
cp)
c3h sp3 carbon in 3-membered ring with hydrogens (equiv.
to c)
atom
general class type description
3
c3m sp carbon in 3-membered ring (equiv. to c)
c4h sp3 carbon in 4-membered ring with hydrogens (equiv.
to c)
c4m sp3 carbon in 4-membered ring (equiv. to c)
c′ sp2 carbon in carbonyl (C=O) group in amide
c" carbon in carbonyl group, not amide (equiv. to c*)
c* carbon in carbonyl group, not amide
c– carbon in carboxylate (COO–) group
c+ carbon in guanidinium group
c= nonaromatic end doubly bonded carbon
c=1 nonaromatic, next-to-end doubly bonded carbon
c=2 nonaromatic doubly bonded carbon
nitrogen types
n sp2 amide nitrogen
na sp3 amine nitrogen
nb sp2 nitrogen in aromatic amine (equiv. to nn)
nh sp2 nitrogen in 5- or 6-membered ring, bonded to
hydrogen
nho sp2 nitrogen in 6-membered ring, next to a carbonyl
group and with a hydrogen (equiv. to nh)
nh+ protonated nitrogen in 6-membered ring
ni sp2 nitrogen in charged imidazole ring (his+) (equiv. to
nh)
nn sp2 nitrogen in aromatic amine
np sp2 nitrogen in 5- or 6-membered ring, not bonded to
hydrogen
npc sp2 nitrogen in 5- or 6-membered ring, bonded to a
heavy atom (equiv. to nh)
nr sp2 nitrogen in guanidinium group (HN=C(NH2)2)
nt sp nitrogen involved in triple bond
nz sp nitrogen in N2
n1 sp2 nitrogen in charged arginine (equiv. to nr)
n2 sp2 nitrogen in guanidinium group (HN=C(NH2)2)
(equiv. to nr)
n4 sp3 nitrogen in protonated amine (equiv. to n+)
n3m sp3 nitrogen in 3-membered ring (equiv. to na)
n3n sp2 nitrogen in 3-membered ring (equiv. to n)
atom
general class type description
3
n4m sp nitrogen in 4-membered ring (equiv. to na)
n4n sp2 nitrogen in 4-membered ring (equiv. to n)
n+ protonated amine nitrogen
n= nonaromatic end doubly bonded nitrogen
n=1 nonaromatic, next-to-end doubly bonded nitrogen
n=2 nonaromatic doubly bonded nitrogen
oxygen types
o sp3 oxygen in alcohol, ether, acid, or ester group
oc sp3 oxygen in ether or acetal (equiv. to o)
oe sp3 oxygen in ester (equiv. to o)
oh oxygen bonded to H (equiv. to o)
op oxygen in aromatic ring (e.g., furan)
o3e sp3 oxygen in 3-membered ring (equiv. to o)
o4e sp3 oxygen in 4-membered ring (equiv. to o)
o′ oxygen in carbonyl (C=O) group
o* oxygen in water
o– oxygen in carboxylate (COO–) group
sulfur types
s sp3 sulfur in sulfide, disulfide, or thiol group
sc sp3 sulfur in methionine (C–S–C) group (equiv. to s)
sh sulfur in sulfhydryl (SH) group (equiv. to s)
sp sulfur in aromatic ring (e.g., thiophene)
s1 sulfur involved in S–S disulfide bond (equiv. to s)
s3e sulfur in 3-membered ring (equiv. to s)
s4e sulfur in 4-membered ring (equiv. to s)
s′ sulfur in thioketone (>C=S) group
s– partial-double sulfur bonded to something that is
bonded to another partial-double oxygen or sulfur
phosphorus
p general phosphorous atom
halogen types
br bromine bonded to a carbon
cl chlorine bonded to a carbon
f fluorine bonded to a carbon
i covalently bound iodine
ion types
atom
general class type description
Br bromide ion
ca+ calcium ion (Ca2+)
Cl chloride ion
Na sodium ion
argon
ar argon atom
silicon
si silicon atom
other
lp lone pair
nu null atom for relative free energy
atom
general class type description
hydrogen types
H hydrogen bonding hydrogen (neutral group)
HA aliphatic or aromatic hydrogen
HC hydrogen bonding hydrogen (charged group)
HMU mu-bonded hydrogen for metals and boron-hydride
HO hydrogen on an alcohol oxygen
HT TIPS3P water-model hydrogen
carbon types
C carbonyl or guanidinium carbon
C3 carbonyl carbon in 3-membered aliphatic ring
C4 carbonyl carbon in 4-membered aliphatic ring
C5R aromatic carbon in 5-membered ring
C5RP for aryl-aryl bond between C5R rings
C5RQ for second aryl-aryl bond between C5RP rings (ortho)
C6R aromatic carbon in a 6-membered ring
C6RP for aryl-aryl bond between C6R rings
atom
general class type description
C6RQ carbon of C6RP type ortho to C6RP pair
CF1 carbon with one fluorine
CF2 carbon with two fluorines
CF3 carbons with three fluorines
CM carbon in carbon monoxide or other triply bonded carbon
CP3 carbon on nitrogen in proline ring
CPH1 CG and CD2 carbons in histidine ring
CPH2 CE1 carbon in histidine ring
CQ66 third adjacent pair of CR66 types in fused rings
CT aliphatic carbon (tetrahedral)
CT3 carbon in 3-membered aliphatic ring, usually tetrahedral
CT4 carbon in 4-membered aliphatic ring, usually tetrahedral
CUA1 carbon in double bond, first pair
CUA2 carbon in double bond, second conjugated pair
CUA3 carbon in double bond, third conjugated pair
CUY1 carbon in triple bond, first pair
CUY2 carbon in triple bond, second conjugated pair
extended-atom carbon types
C5RE extended aromatic carbon in 5-membered ring
C6RE extended aromatic carbon in 6-membered ring
CH1E extended-atom carbon with one hydrogen
CH2E extended-atom carbon with two hydrogens
CH3E extended-atom carbon with three hydrogens
CR55 aromatic carbon-merged 5-membered rings
CR56 aromatic carbon-merged 5- or 6-membered rings
CR66 aromatic carbon-merged 6-membered rings
CS66 second adjacent pair of CR66 types in fused rings
nitrogen types
N nitrogen: planar-valence of 3, i.e., nitrile, etc.
N3 nitrogen in a 3-membered ring
N5R nitrogen in a 5-membered aromatic ring
N5RP for aryl-aryl bond between 5-membered rings
N6R nitrogen in a 6-membered aromatic ring
N6RP for aryl-aryl bond between 6-membered rings
NC charged guanidinium-type nitrogen
atom
general class type description
NC2 for neutral guanidinium group - Arg sidechain
NO2 nitrogen in nitro or related group
NP nitrogen in peptide, amide, or related group
NR1 protonated nitrogen in neutral histidine ring
NR2 unprotonated nitrogen in neutral histidine ring
NR3 nitrogens in charged histidine ring
NR55 N at fused bond between two 5-membered aromatics
NR56 N at fused bond between 5- and 6-membered aryls
NR66 N at fused bond between two 6-membered aromatics
NT nitrogen (tetrahedral), i.e., amine, etc.
NX proline nitrogen or similar
oxygen types
O carbonyl oxygen for amide or related structures
O2M oxygen in Si-O-Al or Al-O-Al bond
O5R oxygen in 5-membered aromatic ring-radicals, etc.
O6R oxygen in 6-membered aromatic ring-radicals, etc.
OA carbonyl oxygen for aldehydes or related
OAC carbonyl oxygen for acids or related
OC charged oxygen
OE ether oxygen / acetal oxygen
OH2 ST2 water-model oxygen
OK carbonyl oxygen for ketones or related
OM oxygen in carbon monoxide or other triply bonded oxygen
OS ester oxygen
OSH massless O for zeolites or related cage compounds
OSI oxygen in Si-O-Si bond
OT hydroxyl oxygen (tetrahedral) or ionizable acid
OW TIP3P water-model oxygen
sulfur types
S5R sulfur in a 5-membered aromatic ring
S6R sulfur in a 6-membered aromatic ring
SE thioether sulfur
SH1E extended-atom sulfur with one hydrogen
SK thioketone sulfur
SO1 sulfur bonded to one oxygen
atom
general class type description
SO2 sulfur bonded to two oxygens
SO3 sulfur bonded to three oxygens
SO4 sulfur bonded to four oxygens
ST sulfur, general: usually tetrahedral
phosphorus types
P6R phosphorous in aromatic 6-membered ring
PO3 phosphorous bonded to three oxygens
PO4 phosphorous bonded to four oxygens
PT phosphorous, general: usually tetrahedral
PUA1 double-bonded phosphorous
PUY1 triple-bonded phosphorus
other
LP ST2 lone pair
atom
general class type description
hydrogen types
h hydrogen, generic
h1 hydrogen, nonpolar
h1+ hydrogen, proton
h1h hydrogen in H2
h1n hydrogen bound to N, Cl
h1o hydrogen bound to O, F
carbon types
c carbon, generic
c1o carbon in carbon monoxide, CO
c2= carbon, SP, two double bonds O=C=O, S=C=S
c2t carbon, SP, triple bond
atom
general class type description
c3 carbon, SP2, generic, 3 bonds
c3” carbon, SP2, carbonyl, two polar substituents
c3# carbon, SP2, in CO32- anion
c3’ carbon, SP2, carbonyl, one polar substituent
c3- carbon, SP2, carboxylate
c3= carbon, SP2, double bond to C (-C=C-)
c3a carbon, SP2, aromatic
c3n carbon, SP2, double bond to N (-C=N-)
c3o carbon, SP2, carbonyl
c4 carbon, SP3, generic, 4 bonds
c43 carbon, SP3, with 3 heavy atoms
c44 carbon, SP3, with 4 heavy atoms
c4o carbon, SP3, bond to oxygen
c4x carbon, SP3, bond to chlorine
nitrogen types
n nitrogen, generic
n1n nitrogen, in N2
n1o nitrogen in NO
n1t nitrogen, SP, 1 triple bond
n2= nitrogen, SP2, 1 double bond, non-aromatic
n2a nitrogen, SP2, 2 partial double bonds, aromatic
n2t nitrogen, SP, 1 triple bond, non-aromatic
n3 nitrogen, SP3, in amines
n3* nitrogen, SP3, in NH3
n3+ nitrogen, SP3, charged
n3a nitrogen, SP2, aromatic
n3h1 nitrogen, SP3, in amines with 1 hydrogen
n3h2 nitrogen, SP3, in amines with 2 hydrogens
n3m nitrogen, SP3, in amides without hydrogen
n3mh nitrogen, SP3, in amides with hydrogen
n3o nitrogen, SP2, in nitro group
n4+ nitrogen, SP3, in protonated amine
atom
general class type description
n4o nitrogen, SP3, in amine oxide
oxygen types
o oxygen, generic
o-2 oxygen, anion in metal oxides (O-2)
o1- oxygen, SP2, in carboxylate
o12 oxygen, SP2, in nitro group (-NO2)
o1= oxygen, SP2, in carbonyl
o1=* oxygen, in CO2
o1c oxygen, in CO
o1n oxygen, in NO
o1o oxygen, in O2
o2 oxygen, SP3, generic
o2* oxygen, SP3, in water
o2a oxygen, SP2, aromatic, in 5-membered ring
o2b oxygen, SP3, bridge atom in anhydrides
o2c oxygen, SP3, in acids
o2e oxygen, SP3, in ethers
o2h oxygen, SP3, in alcohol
o2s oxygen, SP3, in esters
o2z oxygen, in siloxanes and zeolites
o3 oxygen, in H3O+
o3z oxygen, bridge in zeolites
sulfur types
s sulfur, generic
s1= sulfur, 1 double bond (=S)
s2 sulfur, 2 single bonds (-S-)
s2= sulfur, 2 double bonds (=S=)
s2a sulfur, in aromatic ring (thiophene)
s3= sulfur, 3 bonds, 1 is double
s4 sulfur, 4 single bonds
s4= sulfur, 4 bonds, 2 are double
s6 sulfur, 6 single bonds
atom
general class type description
phosphorus types
p phosphorus, generic
p4= phosphorus, in phosphazenes
halogen types
br bromine, generic
br- bromine, anion
br1 bromine, one bond
cl chlorine, generic
cl- chlorine anion
cl1 chlorine, one bond
cl12 chlorine, to a carbon that has 2 X
cl13 chlorine, to a carbon that has 3 X
cl14 chlorine, to a carbon that has 4 X
cl1p chlorine, in phosphazenes
f fluorine, generic
f- fluorine anion
f1 fluorine, one bond
f12 fluorine, to a carbon that has 2 F
f13 fluorine, to a carbon that has 3 F
f14 fluorine, to a carbon that has 4 F
f1p fluorine, in phosphazene
i iodine, generic
i- iodine anion
i1 iodine, with one bond
metal types
Ag silver, metal
Al aluminum, metal
Au gold, metal
Cr chromium, metal
Cu copper, metal
Fe iron, metal
Mo molybdenum, metal
atom
general class type description
Ni nickel, metal
Pb lead, metal
Pd palladium, metal
Pt platinum, metal
Sn tin, metal
W tungsten, metal
metal ion types
ca+ calcium ion (Ca2+)
cu+2 copper ion (Cu2+)
fe+2 iron ion (Fe2+)
mg+2 magnesium ion (Mg2+)
zn+2 zinc ion (Zn2+)
alkali metal and ion types
K potassium, metal
Li lithium, metal
Na sodium, metal
cs+ cesium ion (Cs+)
k+ potassium ion (K+)
li+ lithium ion (Li+)
na+ sodium ion (Na+)
rb+ rubidium ion (Rb+)
zeolite and silicon types
al4z aluminum, in zeolites
si silicon, generic
si4 silicon, generic with 4 bonds
si4c silicon, in siloxane with heavy atoms only
si4z silicon, in zeolites
noble gas types
atom
general class type description
ar argon
he helium
kr krypton
ne neon
xe xenon
atom
general class type description
hydrogen types
d general deuterium (equiv. to h)
dw deuterium in heavy water (equiv. to h*)
h generic hydrogen bonded to C, Si, or H
hc hydrogen bonded to C (equiv. to h)
hi hydrogen in charged imidazole ring (equiv. to hn)
hn hydrogen bonded to N
ho hydrogen bonded to O
hp hydrogen bonded to P (equiv. to h)
hs hydrogen bonded to S
hw hydrogen in water (equiv. to h*)
h* hydrogen in water
h+ charged hydrogen in cation (equiv. to hn)
hscp hydrogen in SPC water model
htip hydrogen in TIP3P water model
carbon types
c generic sp3 carbon
ca general amino acid alpha carbon (sp3) (equiv. to cg)
cg sp3 alpha carbon in glycine
ci sp2 aromatic carbon in charged imidazole ring (his+)
cn sp3 carbon bonded to N (equiv. to cg)
atom
general class type description
3
co sp carbon in acetal (equiv. to c)
coh sp3 carbon in acetal with hydrogen (equiv. to cg)
cp sp2 aromatic carbon (partial double bonds)
cr carbon in guanidinium group (HN=C(NH2)2) (arg)
cs sp2 carbon in 5-membered ring next to S
ct sp carbon involved in triple bond
c1 sp3 carbon bonded to 1 H, 3 heavy atoms (equiv. to
cg)
c2 sp3 carbon bonded to 2 H’s, 2 heavy atoms (equiv. to
cg)
c3 sp3 carbon in methyl (CH3) group (equiv. to cg)
c5 sp2 aromatic carbon in 5-membered ring
c3h sp3 carbon in 3-membered ring with hydrogens
(equiv. to cg)
c3m sp3 carbon in 3-membered ring (equiv. to c)
c4h sp3 carbon in 4-membered ring with hydrogens
(equiv. to cg)
c4m sp3 carbon in 4-membered ring (equiv. to c)
c′ sp2 carbon in carbonyl (C=O) group of amide
c" carbon in carbonyl group, not amide (equiv. to c′)
c* carbon in carbonyl group, not amide (equiv. to c′)
c– carbon in charged carboxylate (COO-) group (equiv.
to c′)
c+ carbon in guanidinium group (equiv. to cr)
c= nonaromatic end doubly bonded carbon
c=1 nonaromatic, next-to-end doubly bonded carbon
c=2 nonaromatic doubly bonded carbon
nitrogen types
n generic sp2 nitrogen in amide
na sp3 nitrogen in amine (equiv. to n3)
nb sp2 nitrogen in aromatic amine (equiv. to n3)
nh sp2 nitrogen in 5- or 6-membered ring, with hydrogen
attached (equiv. to np)
nho sp2 nitrogen in 6-membered ring, next to a carbonyl
group and with a hydrogen (equiv. to np)
nh+ protonated nitrogen in 6-membered ring
ni sp2 nitrogen in charged imidazole ring (his+)
atom
general class type description
2
nn sp nitrogen in aromatic amine (equiv. to n3)
np sp2 nitrogen in 5- or 6-membered ring
npc sp2 nitrogen in 5- or 6-membered ring, bonded to a
heavy atom (equiv. to np)
nr sp2 nitrogen in guanidinium group (HN=C(NH2)2)
nt sp nitrogen involved in triple bond
nz sp nitrogen in N2
n1 sp2 nitrogen in charged arginine
n2 sp2 nitrogen in guanidinium group (HN=C(NH2)2)
n3 sp3 nitrogen with 3 substituents
n4 sp3 nitrogen in protonated amine
n3m sp3 nitrogen in 3-membered ring (equiv. to n3)
n3n sp2 nitrogen in 3-membered ring (equiv. to n)
n4m sp3 nitrogen in 4-membered ring (equiv. to n3)
n4n sp2 nitrogen in 4-membered ring (equiv. to n)
n+ sp3 nitrogen in protonated amine (equiv. to n4)
n= nonaromatic end doubly bonded nitrogen
n=1 nonaromatic, next-to-end doubly bonded nitrogen
n=2 nonaromatic doubly bonded nitrogen
oxygen types
o generic sp3 oxygen
oc sp3 oxygen in ether or acetal (equiv. to o)
oe sp3 oxygen in ester (equiv. to o)
oh oxygen bonded to H
op sp2 aromatic oxygen in 5-membered ring
o3e sp3 oxygen in 3-membered ring (equiv. to o)
o4e sp3 oxygen in 4-membered ring (equiv. to o)
o′ oxygen in carbonyl (C=O) group
o* oxygen in water
o– oxygen in charged carboxylate (COO–) group
oscp oxygen in SPC water model
otip oxygen in TIP3P water model
sulfur types
s sp3 sulfur
sc sp3 sulfur in methionine (C–S–C) group (equiv. to s)
sh sulfur in sulfhydryl (SH) group
atom
general class type description
sp sulfur in aromatic ring, e.g., thiophene
s1 sulfur involved in S–S disulfide bond (equiv. to s)
s3e sulfur in 3-membered ring (equiv. to s)
s4e sulfur in 4-membered ring (equiv. to s)
s′ sulfur in thioketone (>C=S) group
s– partial-double sulfur bonded to something that is
bonded to another partial-double oxygen or sulfur
phosphorus
p general phosphorous atom
halogen types
br bromine bonded to a carbon
cl chlorine bonded to a carbon
f fluorine bonded to a carbon
i covalently bound iodine
ion types
Br bromide ion
ca+ calcium ion (Ca2+)
Cl chloride ion
Na sodium ion
argon
ar argon atom
silicon
si silicon atom
other
lp lone pair
nu null atom for relative free energy calculations
atom
element type charge description
Si sz 2.4 tetrahedral silicon in a zeolite or silicate
O oz -1.2 oxygen in a zeolite or silicate
Al az 1.4 tetrahedral aluminum atom in zeolites
P pz 3.4 phosphorous atom in zeolites
Ga ga 1.4 gallium atom in zeolites
Ge ge 2.4 germanium atom in zeolites
Ti tioc 1.6 titanium (octahedral) in zeolites
Ti titd 2.4 titanium (tetrahedral) in zeolites
Li li+ 1.0 lithium ion in zeolites
Na na+ 1.0 sodium ion in zeolites
K k+ 1.0 potassium ion in zeolites
Rb rb+ 1.0 rubidium ion in zeolites
Cs cs+ 1.0 cesium ion in zeolites
Mg mg2+ 2.0 magnesium ion in zeolites
Ca ca2+ 2.0 calcium ion in zeolites
Ba ba2+ 2.0 barium ion in zeolites
Cu cu2+ 2.0 copper(II) ion in zeolites
F f- -1.0 fluoride ion in zeolites
Cl cl- -1.0 chloride ion in zeolites
Br br- -1.0 bromide ion in zeolites
I i- -1.0 iodide ion in zeolites
S so4 2.8 sulfur in sulfate ion to be used with oz
atom
element type charge description
Fe fe2c 2.0 octahedral Fe(II) ion in clays
Mn mn4c 4.0 manganese (IV) ion to be used with oy
Mn mn3c 3.0 manganese (III) ion to be used with oy
Co co2c 2.0 cobalt (II) ion to be used with oy
Ni ni2c 2.0 nickel (II) ion to be used with oy
Li lic+ 1.0 lithium ion to be used with oy
Pd pd2+ 2.0 palladium(II)
Ti ti4c 4.0 titanium (octahedral) to be used with oy
Sr sr2c 2.0 strontium ion to be used with oy
Ca ca2c 2.0 calcium ion to be used with oy
Cl cly- -1.0 chloride ion to be used with oy
H hocl 1.0 hydrogen in hydroxyl group in clays
P py 5.0 phosphorous atom to be used with oy
V vy 4.0 tetrahedral vanadium to be used with oy
N nh4+ 1.0 united-atom type for ammonium ion to be used with oy
S so4y 6.0 sulfur in sulfate ion to be used with oy
Li lioh 1.0 lithium ion in water to be used with o*
Na naoh 1.0 sodium ion in water to be used with o*
K koh -1.0 potassium ion in water to be used with o*
F foh -1.0 fluoride ion in water to be used with o*
Cl cloh -1.0 chloride ion in water to be used with o*
Be beoh 0.0 beryllium (II) in water to be used with o*
Al al 0.0 aluminum metal
Na Na 0.0 sodium metal
Pt Pt 0.0 platinum metal
Pd Pd 0.0 palladium metal
Au Au 0.0 gold metal
Ag Ag 0.0 silver metal
Sn Sn 0.0 tin metal
K K 0.0 potassium metal
Li Li 0.0 lithium metal
Mo Mn 0.0 molybdenum metal
Fe Fe 0.0 iron metal
W W 0.0 tungsten metal
Ni Ni 0.0 nickel metal
atom
element type charge description
Cr Cr 0.0 chromium metal
Cu Cu 0.0 copper metal
Pb Pb 0.0 lead metal
symbol symmetry
l C2v
s D4h
t Td
o Oh
p D5h
h D2h, D3h
d D∞
∑ ∑
1 Fq j
N ox = Q t – ------- Fq i – -------- Eq. 136
Nm Nb
where Qt is the total charge on the complex, and the sums over Fqi
and Fqj are the sums of formal charges on atoms not bonded to
metals and bonded to metals, respectively. Nm is the number of
metal atoms in the complex, and Nb is the number of metal atoms
bonded to the jth ligand atom.
Table 32 Atom types for the first three rowsa of the periodic table—ESFF (Page 1 of
4)
gener- atom
al class type description
hydrogen types
dw deuterium in heavy water
h generic hydrogen
hi hydrogen in charged imidazole ring (equiv. to h*)
hw hydrogen in water (equiv. to h*)
h* hydrogen bonded to nitrogen, oxygen
h+ charged hydrogen in cations
carbon types
c generic sp3 carbon
ca general amino acid alpha carbon (sp3) (equiv. to c)
cg sp3 alpha carbon in glycine (equiv. to c)
ci carbon in charged imidazole ring (equiv. to cp)
co sp3 carbon in acetals (equiv. to c)
coh sp3 carbon in acetals with hydrogen (equiv. to c)
cp sp2 aromatic carbon with partial double bond
cr c in neutral arginine (equiv. to c=)
cs sp2 aromatic carbon in 5-membered ring next to S (equiv. to cp)
ct sp carbon involved in a triple bond
ct3 sp carbon involved in CO
c1 sp3 carbon with 1 H 3 heavies (equiv. to c)
c2 sp3 carbon with 2 H’s, 2 heavies (equiv. to c)
c3 sp3 carbon with 3 H’s, 1 heavy (equiv. to c)
c5 sp2 aromatic carbon in 5-membered ring
c5p sp2 aromatic carbon in 5-membered big pi ring
c’ carbon in carbonyl (C=O) group
Table 32 Atom types for the first three rowsa of the periodic table—ESFF (Page 2 of
4)
gener- atom
al class type description
c- c in charged carboxylate
c+ c in guanidinium group (equiv. to c=)
c= generic sp2 carbon
nitrogen types
n generic sp2 nitrogen (in amides)
na sp3 nitrogen in amines
nb sp2 nitrogen in aromatic amines
nh sp2 (3 [sp2] 2 [p]) nitrogen in 5-membered ring
nho sp2 nitrogen in 6-membered ring
ni nitrogen in charged imidazole ring (equiv. to nh)
no sp2 nitrogen in oxides of nitrogen
np sp2 nitrogen in 5-membered ring
nt sp nitrogen involved in a triple bond
nt2 central nitrogen involved in azide group
nz sp nitrogen in N2
n1 sp2 nitrogen in charged arginine (equiv. to n=)
n2 sp2 nitrogen (NH2) in guanidinium group (HN=C(NH2)2) (equiv. to n=)
n4 sp3 nitrogen with 4 substituents (equiv. to n+)
n+ sp3 nitrogen in protonated amines
n= sp2 nitrogen in neutral arginine (double bond)
oxygen types
o generic sp3 oxygen in alcohol, ether, or acid group
oa sp3 oxygen in ester or acid
oc sp3 oxygen in ether or acetalsE (equiv. to o)
oh oxygen bonded to hydrogen (equiv. to o)
op sp2 aromatic in 5-membered ring
os oxygen bonded to two silicons
ot oxygen with hybridization sp
o1 oxygen bonded to oxygen
o’ oxygen having a single double bond
o* oxygen in water
o- double bonded oxygen in charged carboxylate COO– (equiv. to o’)
sulfur types
s sp3 sulfur
sp sulfur in an aromatic ring (e.g., thiophene)
Table 32 Atom types for the first three rowsa of the periodic table—ESFF (Page 3 of
4)
gener- atom
al class type description
3
s1 sp sulfur involved in (S-S) group of disulfides
s2d sulfur with oxidation number 4, two double sigma bond
s3d sulfur with oxidation number 4, three sigma bond, (C3v)
s4d sulfur with oxidation number 6, four sigma bond, (Td)
s4l sulfur with coordination number 4 (C2v)
s5l sulfur with coordination number 5 (D4h, C2v)
s5t sulfur with coordination number 5 (D3h)
s6 sulfur with coordination number 6 (D4h, D2h)
s6o sulfur with coordination number 6 (Oh)
s’ S in thioketone group
s- double bonded sulfur in charged phosphate PSS– or PSO– (equiv. to s’)
phosphorus types
p general phosphorous atom
p4d phosphorous atom with oxidation number 5 and 4 sigma bonds (CTd)
p4l phosphorous atom with oxidation number 5 and 3 sigma bonds (C2v)
p5l phosphorous atom with oxidation number 5 and 3 sigma bonds (D4h, C2v)
p5t phosphorous atom with oxidation number 5 and 3 sigma bonds (D3h)
p53 phosphorous atom with oxidation number 5 and 3 sigma bonds (planar)
p6 phosphorous atom with oxidation number 5 and 3 sigma bonds (D4h, D2h)
p6o phosphorous atom with oxidation number 5 and 3 sigma bonds (Oh)
p’ sp2 phosphorous atom
other second-row elements
b boron sp3 atom
bt boron sp atom
b’ boron sp2 atom
Be berillium atom
Be+ berillium cation
Be+2 berillium cation
f fluorine atom
F fluorine anion
Li lithium atom with s orbitals involved in bonding
Li+ lithium ion
ne neon atom
other third-row elements
ar argon atom
Table 32 Atom types for the first three rowsa of the periodic table—ESFF (Page 4 of
4)
gener- atom
al class type description
Al aluminum atom
Al033 aluminum atom with coordination number 3
Al034 aluminum atom with coordination number 4
Al035 aluminum atom with coordination number 5
Al035s aluminum atom with coordination number 5 (D4h)
Al035t aluminum atom with coordination number 5 (D3h)
Al036 aluminum atom with coordination number 6 (D4h, D2h)
Al036o aluminum atom with coordination number 6 (Oh)
cl chlorine atom
Cl chlorine ion
cl’ chlorine atom in oxo acid
he helium atom
Mg magnesium atom
Mg025 magnesium atom with 5 coordinations
Mg025s magnesium atom with 5 coordinations (D4h)
Mg025t magnesium atom with 5 coordinations (D3h)
Mg026 magnesium atom with 6 coordinations (D4h, D2h)
Mg026 magnesium atom with 6 coordinations
o
Mg+ magnesium +1 cation (Oh)
Mg+2 magnesium +2 cation
Na sodium atom
Na+ sodium ion
si silicon atom
si4l silicon atom (D3h, C2v)
si5l silicon atom (D4h)
si5t silicon atom (D3h)
si6 silicon atom (D4h, D2h)
si6o silicon atom (Oh)
si’ sp2 silicon atom
a
Please see $BIOSYM_LIBRARY/esff.frc for heavier elements.
atom
general class type description
hydrogen types
hn2 amino hydrogen
ho2 hydroxyl hydrogen
carbonyl functional groups (C and O)
c_0 carbonyl carbon of aldehydes, ketones
c_1 carbonyl carbon of acid, ester, amide
c_2 carbonyl carbon of carbamate, urea
cz carbonyl carbon of carbonate
o= oxygen double bonded to O, C, S, N, P
o_1 oxygen in carbonyl group
o_2 ester oxygen
oo oxygen in carbonyl group, carbonate only
oz ester oxygen in carbonate
phosphorus types
p= phosphazene phosphorous atom
silicon-related types
si silicon atom
sio siloxane silicon
hsi silane hydrogen
osi siloxane oxygen
noble gas types
he helium
ar argon
kr krypton
ne neon
xe xenon
metal atoms and halogen ions
Ag silver metal
Al aluminium metal
atom
general class type description
Au gold metal
Br bromine ion
Cl chlorine ion
Cr chromium metal
Cu copper metal
Fe iron metal
K potassium metal
Li lithium metal
Mo molybdenum metal
Na sodium metal
Ni nickel metal
Pb lead metal
Pd palladium metal
Pt platinum metal
Sn tin metal
W tungsten metal
zeolite-related types
az aluminium atom in zeolites
oss oxygen atom betweem two silicons
osh oxygen atom in terminal hydroxyl group on silicon
oah oxygen atom in terminal hydroxyl group on aluminium
oas oxygen atom between aluminium and silicon
ob oxygen atom in bridging hydroxyl group
sz silicon atom in zeolites
hb hydrogen atom in bridging hydroxyl group
hoa hydrogen atom in terminal hydroxyl group on alumin-
ium
hos hydrogen atom in terminal hydroxyl group on silicon
aPCFF
also includes all the atom types listed for CFF91 (page 291).
A equivalences, 85
forcefield parameter assignment, 84
ab initio, 11 wildcarding, 85, 87
ABM4 integrator, 196 wildcarding, precedence, 87
compared with Verlet velocity integrator, X, 85
204 atomic positions, poorly defined, 101
absolute free energy atomic velocities, 211
algorithm, 259 atoms
calculation, 258 fixing, 102
conformational searching, 267 forces on, 181
constraining dynamics, 268 types, 79, 283
convergence, 271 typing, 78
dynamics running averages, 272 atom-type charge, 81
errors, 269, 271 Austin, N., 67, 280
example, 264 automatic atom types, 31, 61
ideal solid, 259
λ intervals, number, 269
reference state, 263, 265 B
setting up, 267
spring constants, 268, 269, 272 Bash, P. A., 279
Adams–Bashforth–Moulton integrator, 196 Becker, J. M., 275
adiabatic compliance tensor, 210 Berendsen equation, 217
adiabatic compressibility, 210 Berendsen, H. J. C., 217, 224, 226, 273, 278, 279
adiabatic ensembles, 205 Beveridge, D. L., 180, 277
Alagona, G., 280 BKS forcefield, 65
Allen, M. P., 116, 210, 222, 227, 273 bold type, meaning, 7
Allinger, N. L., 70, 276, 279 bond hybridization, 50
AMBER, 70 bond increments, 31, 61
bonds
atom types, 55
atom types for carbohydrates, 55 between symmetrically related objects, 120
characteristics, 22 constraints, 109, 237
distance-dependent dielectric, 126 Born–Oppenheimer equation, 11
functional form, 54 Born, M., 11, 273
hydrogen-bond term, 54 Boyd, D. B., 274
1–4 nonbond interactions, 123 Brady, J. W., 275
amino acids, 23, 57, 61 Brooks, B. R., 22, 56, 273
Andersen, H. C., 209, 227, 237, 273 Brooks, C. L., 255
angles Brooks, C. L., III, 127, 234, 273
constraints, 109, 237 Brown, D., 227, 273
atom types Brown, F. K., 279
assigning, 79 Bruccoleri, R. E., 273
asterisks, 85 Brunger, A. T., 273
P
Q
Parrinello, M., 209, 228, 277
partition function, 259 quantum effects, 180
peptides, 23 quantum mechanical probability function, 14
periodic boundary conditions, 224, 225 quartz, 144
definition, 113 Quirke, N., 180, 278
periodic systems
disordered, 137 R
dynamics, 208, 209, 222, 224
Ewald calculations, 143 radius of gyration, 238
Peterson, B. K., 277 Rahman, A., 228, 277
Pettitt, B., 273 Rappé, A. K., 21, 42, 43, 44, 83, 273, 274, 278
Pickett, S. D., 67, 277 rattle command, 109
polymer forcefield, 62 Ravimohan, C., 255
polymers, 53 Ray, J. R., 207, 210, 278
polysaccharides, 54, 55 reading models, 76
polyvinylidene fluoride forcefield, 61, 64 Reeves, C. M., 165, 274
T Universal forcefield
atom type naming, 43
Tai, J. C., 276, 279 availability, 35
Tembe, B. L., 180, 280 characteristics, 21
temperature, 211 charges, 44
and average kinetic energy, 212 implementation, 42
and correct statistical ensemble, 214 parameter generation, 43
calculation of, 213 versions, 44
control, 220
damping, 217
distribution of atomic velocities, 211 V
integration errors, 203 VALBOND
nonperiodic system, 213 characteristics, 21
nonzero, 189 valence exclusions, 123
periodic system, 213 valence interactions, 16
template atoms, 103 van Beest, B. W. H., 65, 280
template forcing, 103, 155 van der Waals
functional forms, 103 combination rules, 124
tensile stress, 221 cutoff distance and, 129, 130
Tesar, A. A., 62, 280 Ewald calculations, 144
tethering, 101, 105 interaction potential, 199
functional forms, 105 interactions, 28, 54, 60
Teukolsky, S. A., 278 van Gunsteren, W. F., 273
Thacher, T. S., 277 van Santen, R. A., 280
thermal expansion, 210, 211 Varshneya, A. K., 62, 279, 280
thermodynamic cycle, 180 Verlet leapfrog integrator, 194, 195
thermodynamic ensembles, 191 Verlet velocity integrator, 194, 195
thermodynamic response function, 207 compared with ABM4 integrator, 204
thermodynamic temperature, 213 Verlet, L., 195, 280
Thomas, J. M., 277, 280 Vetterling, W. T., 278
Tildesley, D. J., 116, 210, 222, 227, 273 vibrational calculations, 185
timestep length in dynamics, 197 computational costs, 187
Tolleanaere, J. P., 264 cross terms and, 187
torsions entropy, 187
forcefield accuracy and, 187
forcing, 110
free energy, 182
restraints, 110, 111 frequencies, 60, 167, 182, 185
trajectory from potential energy surface, 184
animation, 238 harmonic, 153
contents, 238 imaginary frequencies, 186
definition, 193 normal mode analysis, 167
length, 241 prerequisites, 185
uses, 238 quality, 185
transition states, 183 quantum mechanical equation, 186
uses, 182
virial, 210
U viscous fluids, 234
united-atom representation, 54 volume, periodic boundary conditions, 222
W
Waldman, M., 20, 125, 276, 280
Warshel, A., 180, 276, 280
Watanabe–Austin forcefield, 67
Watanabe, K., 67, 280
water, 57
constrained, 237
fixed-geometry model, 109, 237
SPC, 109, 237
TIP3P, 109, 237
Weiner, P., 280
Weiner, S. J., 22, 53, 70, 280, 290
Wiberg, K. B., 55, 280
Williams, D. E., 68, 280
Wilson, E. B., 28, 183, 280
Wolff, J., 274
Wolynes, P. G., 277
Woodcock, L. V., 62, 280
Y
Yang, Y., 279
Yan, L., 279
Yashonath, S., 67, 274, 280
Yuh, Y., 279
Z
zeolite forcefield, 61, 62
zero-point corrections, 180, 182, 186
Zirl, D. M., 62, 274, 281