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Proposing Institution

Physik-Departement T38, TUM
Project Manager

Prof. Dr. Martin Zacharias
James-Franck-Str. 1
85748 Garching
Conformational changes and transitions often mediate the function of proteins and are also frequently involved in association processes. Experimental structural analysis provides at most the atomic structures of the unbound partners and of the final complex, however, the process of conformational changes cannot be uncovered by experiments alone. Molecular Dynamics (MD) simulations offer, in principle, the possibility to analyze the complete process at atomic detail. We plan to use advanced sampling approaches to study the process of amyloid fibril aggregation and the mechanism of global changes in the Hsp90 chaperone protein that mediate folding of protein molecules. As main approach we plan to perform Umbrella Sampling simulations in combination with Hamiltonian replica exchange (H-REMD) to allow rapid and converged calculations of free energy landscapes for conformational transitions. Specifically, the association/dissociation of amyloid peptides at a growing amyloid tip and global domain motions of Hsp90 substructures will be investigated. The combined Umbrella Sampling and H-REMD approach shows very good scaling on the SuperMUC parallel supercomputer. The simulations will give atomic resolution insight into the mechanism of amyloid formation and associated conformational changes and also insight into the mechanism of Hsp90 to assist protein folding.

Impressum, Conny Wendler