Computer-aided drug design (CADD) uses computational methods to simulate drug-receptor interactions and has reduced drug research duration by at least 5 years. CADD techniques rely on bioinformatics tools, databases, and applications. Quantitative structure-activity relationship (QSAR) modeling correlates compound structural properties with biological activities and has provided a basis for optimizing ligand molecules to improve activity. CADD approaches include structure-based modeling using protein-ligand docking and ligand-based modeling analyzing statistical relationships between ligand structural groups and biological effects.

1. Role of Computer in Drug Design
PRESENTED BY:-ANKIT TIWARI

2. PRESESNTED BY

3. Drug Design / drug discovery
What’s a drug?
A substance that treats/cure a disease.
A small molecule that interacts with a target, (often protein involved in the disease
process; activator/inhibitor)
Drug discovery:
The process of finding such a small molecule – combination of approaches
Drug discovery or drug design?
In principle: “Design” is more rational and targeted, and “discovery” is more
serendipitous. But design and discovery share a lot and are ~ synonymous in a
pharmaceutical context.

4. Drug discovery market
Gigantic economic importance: 10 years & $200 to $1,900
million to develop a drug
25 new molecules /year
in millions US$ Revenue R&D income
Johnson & Johnson 53,324 7,125 11,053
Pfizer 48,371 7,599 19,337
GlaxoSmithKline 42,813 6,373 10,135
Novartis 37,020 5,349 7,202
Sanofi-Aventis 35,645 5,565 5,033
Hoffmann–La Roche 33,547 5,258 7,318
AstraZeneca 26,475 3,902 6,063
Merck & Co. 22,636 4,783 4,434
Abbott Laboratories 22,476 2,255 1,717
Wyeth 20,351 3,109 4,197
> $340 billion http://en.wikipedia.org/wiki/List_of_pharmaceutical_companies
Intense scientific activity: very interdisciplinary approach

5. The drug discovery and design workflow:
Target identification
Discovery and design
(hit/lead/optimisation)
Biology: assay (binding/activity; in
Chemistry: synthesis
vitro / in vivo,)
drug development:
Pharmacology / testing

6. The long and winding road to drug discovery
Computational chemistry /Molecular modeling
useful across the pipeline,
but
very different techniques
aim for success,
but if not:
fail early, fail cheap

7. Role of Computers
• In early 90’s there was a deal of optimism that
computer’s will play a major role in the
improvement of drug design.
• It reduced at-least 5 year’s of research
duration.

8. Computer aided drug
design(CADD)
• Computer aided drug design is a specialized
discipline that uses computational methods to
stimulate drug receptor interactions.
• CADD technique are dependent on
bioinformatics tools, databases &
applications.

9. What is QSAR?
• QSAR depict an attempt to correlate structural
property of compounds with biological activities.
• Such developments have provided a sound basis for
the generation of 3D Quantitative Structure Activity
Relationship (QSAR) for further refinement of the
ligand molecule in terms of chemical structure so as to
improve biological activity.
• Such physiochemical descriptors which indulge
parameters to account for hydrophobicity, electronic
properties, steric effects, etc. can be determined by
computational methods.

10. Bioinformatics

11. Two pathways to drug discovery / drug design
Structure-based
Structure-based don’t know receptor,
know receptor, known ligands
don’t known ligands
?
What will be happy in there?
Protein/ligand interactions Statistical analysis of what group(s)
structure/biophysics are important for biological activity
docking

12. Receptor interaction

13. Structure based
Uses protein structure directly
CADD: Protein-ligand docking

14. Ligand based
• Binding of ligand to the receptor may include
hydrophobic, electrostatic and hydrogen
bonding interactions.
-Derive information from ligand structures
-Protein structure not always available
• 40% of all prescription pharmaceuticals target GPCRs
-Protein structure has large degree of flexibility
• Structure deforms to accommodate ligands or gross
movements occur on binding