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APPROACHES FOR
DRUG DESIGN
SEMINAR BY:
T.SRAVYA
Drug design
Drug designing is an
process of finding new
medications based on the
knowledge of the biological
target.
TWO APPROACHES
1. RECEPTOR BASED
APPROACH
Analog Based
Drug Design
Structure Based
Drug Design
Homology Modeling
Receptor Mapping
Docking QSAR
Quantum
Molecular Dynamics PCA Mechanics for
Quantum
Simulations Alignment
Mechanical
(BRABO) ANN
Rigid Docking CoMFA
Simulated Annealing GA CoMSIA
FlexiDock
Quantum
Monte Carlo Mechanical
Simulations SINGLE MOLECULE Descriptors
Experimental
Information: The active
site can be identified
based on the position of
the ligand in the crystal
structures of the protein-
ligand complexes
Ligand
.
Examples of Docked
structures
HIV protease inhibitors COX2 inhibitors
Exact Receptor Structure is not
always known
• Receptor Mapping
R2 R1
7.5-8.5Å
Anionic site
6.5Å
Focus of charge
*
Cavity for part of piperidine ring
QSAR
• pi= biological
activity
• d1, d2 =
descriptors( cal
culated
structural
properties)
QSAR MODELLING
APPROACHES
3D-QSAR
A.CoMFA
VARIABLE QSAR SELECTION APPROACHES
A.LINEAR MODEL
B.NON LINEAR
3D QSAR
3D QSAR
Compound Number Biol. Activity Steric
Interactio
S001
1 1.07
2 0.09
3 0.66
CoMFA 3D-QSAR
Problems:
The molecules must be optimally
aligned.
Flexibility of the molecules.
3D-QSAR of CYP450cam with
CoMFA
• Forecasting of biological
activity
•Selection of proper
substituents
•Drug receptor interactions
•Pharmacokinetic information
•Bioisosterism
GENE BASED
APPROACH
.
Gene-based Approach
√ Gene Therapy
Pote
33
Gene-based Approach
√ Gene Therapy – Basic Steps
34
Gene-based Approach
√ Gene Therapy – Basic Steps
• Discover Genes
• Design Replacements
• Deliver to cell / body
• Ensure Incorporation
• Detect Function
• Ensure Stability
• Test Toxicity
• Test long-term effects
35
Gene-based Approach
√ Gene Therapy – Delivering Genes
Basic Methods
Method
Physical Methods 36
√ Delivering Genes – Cells
37
.
THANK YOU