Lecture GK-9

Side-chain modelling

Aims

• To review the amino-acid residue side-chains.
• To introduce an approach to detecting steric overlap efficiently.
• To introduce the terms used in calculating a molecule's potential energy.
• To introduce Monte Carlo methods and simulated annealing.

Objectives

After this lecture you will:

• be aware of the degrees of freedom in amino-acid residue side-chains;
• understand how side-chain rotamers are used in the modelling process;
• understand how to detect steric overlap efficiently;
• know the terms that are typically used in a potential energy function;
• understand the Metropolis procedure and simulated annealing.

Supplementary Material

The concept of side chain rotamers is introduced in:

Ponder, J.W. and Richards, F.M. (1987) Tertiary templates for proteins: Use of packing criteria in the enumeration of allowed sequences for different structural classes. J. Mol. Biol., 193, 775-791 (PubMed)

The use of a backbone-dependent rotamer library in modelling protein side-chains is described in:

Bower, M.J., Cohen, F.E. and Dunbrack, R.L. (1997) Prediction of Protein Side-chain Rotamers from a Backbone-dependent Rotamer Library: A New Homology Modeling Tool. J. Mol. Biol., 267, 1268-1282 (PubMed)

A constraint logic programming approach to side-chain placement is described in:

Swain, M.T. and Kemp, G.J.L. (2001) A CLP approach to the protein side-chain placement problem. In Walsh, T. (ed.) Principles and Practice of Constraint Programming - CP2001, Lecture Notes in Computer Science (vol. 2239), Springer-Verlag, Berlin, pp 479-493. (PDF)

Michael Levitt has produced some useful lecture slides that include descriptions of the protein folding problem, molecular simulation and structure prediction by energy minimisation.

There is an on-line description of simulated annealing and the Metropolis algorithm at:

Carr, Roger "Simulated Annealing." From MathWorld--A Wolfram Web Resource, created by Eric W. Weisstein. http://mathworld. wolfram.com/SimulatedAnnealing.html