Laufer Center Seminar

Claus Wilke

Assistant Professor, Section of Integrative Biology, and Center for Computational Biology and Bioinformatics

University of Texas at Austin

 A structural perspective on protein molecular evolution

The substitution patterns of protein-coding genes are strongly shaped bythe
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.