VPS2141 - Computational Chemistry

Leader: Dr David Chalmers

Offered

Parkville First semester 2008 (Day)

Synopsis

An introduction to the techniques and applications of molecular modelling with particular emphasis on methods used in drug design. The unit contains two streams:

1. modelling methods; which introduces quantum mechanics, molecular mechanics, energy optimisation and molecular simulation and
2. modelling applications; which covers quantitative structure-activity relationships (QSAR), pharmacophores, structure-based drug design and homology modelling.

Objectives

At the completion of this unit the student will have the following. A broad understanding of computational chemistry and its application to drug bimolecular problems. An understanding of common molecular modelling terminology. An appreciation of the factors involved in performing quantum mechanical (QM) calculations and the information that these calculations can provide. An appreciation of molecular mechanisms energy calculations and the information that these calculations can provide. An understanding of the components making up molecular mechanic force fields including bond stretching, angle bending and dihedral angle terms and nonbonded interactions (van der Waals and electrostatic). An understanding of molecular potential energy surfaces and the concepts of global and local minima. - An appreciation of energy optimisation methods including steepest descents and conjugate gradient methods. An appreciation of approaches to finding global energy minima.
An understanding of the Boltzmann distribution and the relationship between temperature and the population of energetic states. An appreciation of molecular simulation methods. An understanding of drug physicochemical properties including electronic, steric and hydrophobic characteristics. An understanding of the statistical methods used to develop QSAR equations. An appreciation of the application of QSAR in drug discovery. An appreciation of impact of drug physicochemical parameters on biopharmaceutical properties. An understanding of the pharmacophore concept and its use in drug discovery. An appreciation of structure and ligand-based drug design an an appreciation of homology modelling methods and the ability to use a specific molecular modelling package to study molecular conformation and analyse drug-receptor interactions.

Assessment

Practical work / tests 30%; Examination 70%.

Contact hours

Lectures/Tutorials:36 x 1 hours and Practicals: 9 x 4 hours.

Prerequisites

VPS1041 Mathematics for pharmaceutical scientists, VPS1022 Organic chemistry II and VPS1072 Physical chemistry II.