Lecture GK-13

Protein surfaces and protein-protein docking

Aims

• To introduce alternative definintions of molecular surface.
• 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.

Objectives

After this lecture you will:

• understand how a probe sphere is used in defining the solvent accessible surface and the molecular surface;
• be aware of spherical harmonic surfaces;
• understand, in principle, how surface skins can be used in predicting protein docking conformations;
• understand how a probe sphere is used in defining a polyhedral representation of a protein's shape;
• understand how propensities can be used to predict binding sites.

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). This appendix includes some references to papers on molecular surface representation by Michael Connolly. In addition to these, Connolly has written an online 2D demo (Java) of molecular surface calculations and an interesting review article.

Voronoi and Delaunay constructions are illustrated in Figures 1 and 2 in these papers:

Gerstein, M., Tsai, J. and Levitt, M. (1995) The volume of atoms on the protein surface: calculated from simulation, using Voronoi polyhedra. J. Mol. Biol., 249, 955-966 (PubMed)

Tsai, J., Taylor, R., Chothia, C. and Gerstein, M. (1999) The packing density in proteins: standard radii and volumes. J. Mol. Biol., 290, 253-266 (PubMed)

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. (PubMed)