Lecture 10

Docking; Multi-resolution modelling

Aims

• To describe alternative ways of representing molecular surfaces.
• To introduce the protein docking problem, and the Hex protein docking program.
• To describe a polyhedral representation of macromolecular shape and its application in predicting binding surfaces.
• To describe a method for combinatorial docking.
• To introduce structural proteomics.

Objectives

After this lecture you will be able to:

• describe, in principle, how surface skins can be used in predicting protein docking conformations;
• describe how a probe sphere is used in defining a polyhedral representation of a protein's shape;
• discuss how propensities can be used to predict binding sites;
• explain how combinatorial docking can be used to predict the conformations of large macromolecular complexes;
• describe the problem of fitting high-resolution molecular structures into envelopes derived from low-resolution data.

Supplementary Material

Some of the lecture slides are available on-line (PDF).

A brief description of the molecular polyhedral shape representation program is given in an appendix of my PhD thesis (PDF, local access only).

For information on spherical harmonic surface representation and protein docking, see Dave Ritchie's web pages. From there you can download PDF versions of the papers about this work and slides from Dave Ritchie's presentations.

Surface triplet propensities are described in: Mehio, W., Kemp, G.J.L., Taylor P. and Walkinshaw, M.D. (2010) Identification of protein binding surfaces using surface triplet propensities. Bioinformatics, 26, 2549-2555 ( doi:10.1093/bioinformatics/btq490)

An approach to combinatorial docking is described in: Inbar, Y., Benyamini H., Nussinov R. and Wolfson H.J. (2005) Prediction of multimolecular assemblies by multiple docking. J. Mol. Biol., 349, 435-447 (doi:10.1016/j.jmb.2005.03.039)

"The Inner Life of a Cell" is the result of a collaboration between scientists at Harvard University and a scientific animation company. An extended version with commentary is available on the Harvard University web site.