MOLECULAR MODELING AND DRUG DESIGN (Elective III) syllabus, JNTU (2007-2008)

UNIT I: INTRODUCTION TO MOLECULAR MODELLING

Introduction to Molecular Modelling. What are models used for? Areas of application – Single

molecule calculation, assemblies of molecules. Reaction of the molecules. Drawbacks of

mechanical models as compared to graphical models. Co-ordinate systems two – matrix,

potential energy surface.

UNIT II – QUANTUM MECHANICS

Postulates of quantum mechanics, electronic structure calculations, ab initio, semi-empirical

and density functional theory calculations, molecular size versus accuracy. Approximate

molecular orbital theories.

UNIT III: EMPIRICAL FORCE FIELD MODELS

Molecular Mechanisms, energy calculations, Bond stretch, angle bending, torsional term.

Electrostatic interaction- Van der waals interactions. Miscellaneous interaction.

UNIT IV – MOLECULAR DYNAMICS

Introduction, Molecular Dynamics using simple models. Dynamics with continuous potentials.

Constant temperature and constant dynamics. Conformation searching, Systematic search.

Applications to protein folding

UNIT V – COMPARATIVE PROTEIN MODELING

Modelling by Homology-the alignment, construction of frame work ,selecting variable regions,

side chain placement and refinement, validation of protein models –Ramchandran plot,

threading and ab initio modeling.

UNIT VI: ANALOG BASED DRUG DESIGN

Introduction to QSAR. lead module, linear and nonlinear modeled equations, biological

activities, physicochemical parameter and molecular descriptors, molecular modelling in

drug discovery.

UNIT VII: STRUCTURE BASED DRUG DESIGN

3D pharmacophores ,molecular docking, De novo Ligand design, Free energies and solvation,

electrostatic and non-electrostatic contribution to free energies.

UNIT VIII: FURTHER APPLICATIONS ON THE DESIGN OF NEW MOLECULES

3D data base searching and virtual screening, Sources of data, molecular similarity and

similarity searching, combinatorial libraries – generation and utility,

TEXTBOOKS

1. Principles and applications of modelling by Leach

2. Molecular Modelling by Hans Pieter,Heltje & Gerd Folkens, VCH.

REFERENCES:

1. Chemical Applications of Molecular Modelling by Jonathan Goodman.

2. Computational Chemistry by Guy H, Grant & W. Graham Richards, Oxford University

Press. April 1985