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BP: Fachverband Biologische Physik

BP 25: Protein Structure and Folding

BP 25.3: Talk

Thursday, February 28, 2008, 15:00–15:15, PC 203

Relation of Evolutionary Dynamics to Molecular Mechanics — •Kay Hamacher — Bioinformatics & Theo. Biology Group, Dept. of Biology, Technische Universität Darmstadt, Schnittspahnstr. 10, 64287 Darmstadt, Germany

We investigate the connection between sequence evolution under selective pressure induced by drugs and the functional and molecular-stability characteristics of a protein.

To this end we analyze sequence data of the human immunodeficiency virus (HIV) type 1 protease for more than 45,000 patients. We then formulate a chemo-physical-model for the stability and the functional modes of the protease and correlate the findings on the sequence evolutionary dynamics to extensive in-silico-mutagensis studies performed with this chemo-physical-model. First we derive a physical explanation for the particular important mutation V82F-I84V.

In a second step we discuss interactions in the β-sheet dimerization interface to be most important for maintaining function and stability of the protease. These interactions are at the same time evolutionary conserved - implications of and comparisons to experimental and other theoretical results are finally discussed.