A structural perspective on protein molecular evolution
The substitution patterns of protein-coding genes are strongly shaped by the 3-dimensional structure of the expressed protein. For example, solvent-exposed residues tend to accumulate mutations much more rapidly than buried residues. To properly account for these effects in comparative sequence analysis, we need to develop methods that can analyze sequences in a structural context. We have started to develop such methods, and can, for example, identify sites with significantly elevated or reduced substitution rate given their location in the protein structure. I will discuss the application of such methods to viral proteins. I will also discuss the evolution of transmembrane proteins, and will show that the membrane environment creates a unique evolutionary constraint. Finally, I will discuss a novel method of calculating a residue's relative solvent accessibility (RSA). RSA is a crucial ingredient in the evolutionary models we develop, and I will demonstrate that our method overcomes an important flaw in current RSA calculations.
Claus Wilke is Assistant Professor at the University of Texas, Austin, and in the Section of Integrative Biology of the Center for Computational Biology and Bioinformatics as well as the Institute for Cell and Molecular Biology.For more information, see http://www.icmb.utexas.edu/profile/profile_claus_wilke.asp