JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD

Course Objective

The topics are framed to enhance the student’s knowledge in the various areas of

molecular modelling, molecular docking, pharmacophore concepts, drug design techniques with detail concepts of all the mentioned areas.

Course Outcome

This enables the students to get a broad idea on the drug discovery mechanisms,

its related terms and concepts of designing of drugs.

UNIT - I

Molecular modelling: Molecular Mechanics, Quantum Mechanics, Energy minimization, geometry optimization, conformational analysis, global conformational minima determination; approaches and problems. Bioactive vs. Global minimum conformations. Automated methods of conformational search. Advantages and limitations of available software. Molecular graphics. Molecular properties, reactivity, Homo, Lumo, Electrostatic potential, Solvent accessible surface.

UNIT - II

Pharmacophore concept: Pharmacophore mapping, methods of conformational search used in pharmacophore mapping. Comparison between the popular pharmacophore methods like Catalyst/HipHop, Disco Tech, GASP with practical examples, 3D QSAR Techniques.

UNIT - III

Design of drugs for the following biological targets Agent acting on enzymes: DHFR, HIV-protease HMG-CoA Reductase, Phosphodiesterase, ACE, Transpeptidase, β-lactamase. Agents acting on receptors: PPAR, protein kinases. Agents acting on Nucleic acids: Topoisomerase, DNA and RNA polymerase, HIV-Reverse transcriptase

UNIT - IV

Molecular docking: Rigid docking, flexible docking, manual docking. Advantages and disadvantages of Flex-X, Flex-S, Autodock and Dock softwares, with successful examples. Molecular dynamics: Dynamics of drugs, biomolecules, drug-receptor complexes, Monte Carlo simulations and Molecular dynamics in performing conformational search and docking. Estimation of free energy from dynamical methods.

UNIT - V

De Novo drug design techniques: Receptor/enzyme cavity size prediction. Predicting the functional components of cavities, designing drugs fitting into cavity. Active site analysis structure – based drug design. Informatics methods in drug design: Informatics methods in drug design: Brief introduction to bioinformatics, chemoinformatics.

REFERENCE BOOKS:

• 1. Robert GCK, ed., “Drug Action at the Molecular Level” University Prak Press Baltimore.
• 2. Martin YC. “Quantitative Drug Design” Dekker, New York.
• 3. Lien EJ. SAR “Side effects and Drug Design” Dekker, New York.
• 4. William H, MalickJB “Drug Discovery and Development” Humana Press Clifton.
• 5. Molecular Modelling, by A. R. Leach
• 6. Organic Chemistry of Drug Design and Drug Action, by R.B. Silverman
• 7. Practical Applications of computer aided drug design, by P.S. Charifson
• 8. Molecular modeling in Drug Design, by C. Cohen
• 9. Chemical Applications of Molecular modeling, by J. Goodman
• 10. Pharmacophore perception, by O. F. Guner
• 11. Current Concepts in Drug Design, T Durai Ananda Kumar, Pharma Med Press M.Pharm I Year I Sem (Pharmaceutical Chemistry)