Autodock Protocol

By
Sasikala Rajendran
Research Scholar
Bharathidasan
Univeristy

Program Needs to Download

Python 2.7.9
Cygwin Terminal Package (Offline Installer

Cygwin.dll)
Mgl Tools package
Autodock Suite for Windows
Autogrid.exe
Autodock.exe

Discovery studio Accelrys package

Installation
Install the package in the following order
Install python 2.7.9 in any drive. Care should be
taken while installing python and other tools for
Admin restriction.
Python installation is followed by MGL tools
package in the same drive where python get
installed
Autodock suite for windows should get install in
the folder where MGL tools get installed.
Ex: D:/MGL Tools 1.5.9/
Discovery studio Acclerys software package could
be installed in the default location.

Important Files to run

Autodock
Autodock.exe
Autogrid.exe
Protein/Receptor in .pdb file format
Ligand/Inhibitor in .pdb format
Cygwin.dll
AD4.1_bound.dat file
AD4_parameters.dat

Steps in Docking
Protein preparation
Ligand preparation
Create .pdbqt file of Receptor and ligand
Setup Autogrid file (.gpf)
Setup Autodock file (.dpf)
Run Autogrid and Autodock commands
Analyze the results

Receptor - Ligand
Download three Dimensional srtucture of

the target protein / Receptor from Protein

Data Bank in .pdb format (Ex: 3RFT.pdb)
Download 3D structure of the Ligand/
inhibitor Pubchem compound database in
.sdf Format (data.sdf)
Note : Resolution of the protein >2A 0
Preferrable : X-ray diffraction
Ligand : 3D structure in sdf format and cross verify its Molecular weight

Protein Preparation
Remove non protein species like water, hetero

atoms , other ligand bound to the protein while

crystallization using Discovery studio packageAccelrys
Note : we can select the chain of interest in .pdf
format for docking.
For Example: 3RFT.pdb has 3 chains. 3RFTA/3RFT B/3
RFT C.
Select the chain of interest and remove other chains.
(in certain cases the catalytic site is formed by the
interaction of chains. In this case keep both chains)
Save it in .pdb format. Put it in the folder where MGL
tools and autodock suite get installed
Note

:Make sure you have a single copy of the protein in the file

Protein Preparation with ADT

Before proceed for docking protein must be

prepare so that it can be saved in .pdbqt

format.
Polar hydrogen atoms need to add to the
protein .
File -> Edit -> Hydrogens -> polar hydrogen
Charges need to add
File - > Edit -> Charges -> Gasteiger
charges.
Note : you can save it in .pdbqt format.

Ligand Preparation
Download 3 D structure of the ligand from

Pubchem compound database of NCBI

repository in .sdf format
Note : care should be followed while
downloading the 3D structure of ligand. Cross
verify its molecular weight, its isomer (D or L
isomer) , metal coordinates etc.,
Ex : data.sdf
Open the ligand in Discovery studio package
(Accelrys)
Save it in .pdb format (Galactarate.pdb)

Ligand Preparation with ADT

Open the ligand with ADT tool
Ligand - > input -> open..
(default input format of the file is .pdbqt. So change it to All
files.)
(ADT automatically compute Gasteiger charges and checks for
polar and non polar hydrogen atoms.)

Ligand -> Torsion Tree - >Detect Root

(ADT determines which atom fits its idea of the best root and marks

it with a green sphere)

Ligand -> Torsion Tree -> Choose Torsions

(Make all active bonds non-rotatable then click on Make all rotatable bonds
rotatable.)

Ligand - > Torsion Tree -> Set Number of Torsions.

(type 6 in the entry and then press <Enter> on your keyboard)

Ligand - > output -> save as pdbqt

Grid Parameter File (.gpf)

Grid - > Macromolecule - > choose
(select the prepared protein 3RFT.pdb. This will

automatically convert the protein .pdbqt format.

ADT checks for the charges and merges polar and
non polar hydrogen)
Grid - > Set Map Types -> open
(open the ligand which is saved in 3RFT.pdbqt
format)
Grid - > Grid Box
(Use the thumbwheels to set the numbers of points to 60, 60,
and 66. You can do this by clicking and dragging on the
wheel )

Grid - > output -> save GPF (3RFT-Galactarate.gpf)

Dock Parameter File (.dpf)

Docking - > Macromolecule - > Set Rigid

Filename -> select 3RFT.pdbqt

Docking - > Ligand - > Choose
(Galactarate.pdbqt)
Docking - > Search parameters -> Genetic
Algorithm
(Accept the default settings)
Docking - > Docking Parameters
(Accept the default settings)
Docking - > Output - > Lamarckian GA (GA LS)
(save it in .dpf format 3RFT-Galactarate.dpf)

Run Autogrid
Run - > Run Autogrid

Set Program Pathname and Parameter

File name and Log File Name
Launch Auto grid

Run Autodock
Run - > Run Autodock

Set Program Pathname and Parameter File name and Log

File Name
Launch Auto dock
This will create docking log file .dlg file (3RFTGalctarate.dlg)
Note :
Autogrid and Autodock must be run in the directory where
the macromolecule , ligand, gpf, dpf and map files.

Analyze the results

Analyze -> Docking-> open (.dlg file)
Analyze - >macromolecule (3RFT.pdbqt)
Analyze - > conformation - > play, rank by

energy