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Proposing Institution

Assistant Professorship Computergestützte Biokatalyse,TUM
Project Manager

Dr. Ana Gamiz-Hernandez
Lichtenbergstr. 4
85747 Garching
Heat shock protein 90 (Hsp90) is a molecular chaperone essential for the folding and stabilization of a wide variety of client proteins in eukaryotes. Many of these processes are associated with cancer and other diseases, making Hsp90 an attractive drug target. Previous studies show that Hsp90 is a highly flexible protein that can adopt a wide range of distinct conformational states, which in turn are tightly coupled to the ATPase activity of the enzyme. In this project, we perform classical atomistic molecular dynamics (MD) simulations, free energy calculations, and hybrid quantum mechanics/classical mechanics (QM/MM) simulations on both monomeric and full-length dimeric models of Hsp90 in order to systematically probe how long-range effects in the global Hsp90 structure regulate ATP-binding and hydrolysis. The simulations are performed in close combination to in-house biophysical experiments (NMR, SAXS, FRET). The study is likely to provide important insight into the molecular mechanism and regulation of Hsp90.

Impressum, Conny Wendler