Douglas Tsao - Ab initio folding of proteins with all-atom discrete molecular dynamics

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      Publication Details (including relevant citation   information):

      Ding, F., Tsao, D., Nie, H., and Dokholyan, N. V.,   Structure, 16:1010-1018, (2008)


      Discrete   molecular dynamics (DMD) is a rapid sampling method used in   protein folding and aggregation studies. Until now, DMD was used   to perform simulations of simplified protein models in   conjunction with structure-based force fields. Here, we develop   an all-atom protein model and a transferable force field   featuring packing, solvation, and environment-dependent hydrogen   bond interactions. We performed folding simulations of six small   proteins (20-60 residues) with distinct native structures by the   replica exchange method. In all cases, native or near-native   states were reached in simulations. For three small proteins,   multiple folding transitions are observed, and the   computationally characterized thermodynamics are in qualitative   agreement with experiments. The predictive power of all-atom DMD   highlights the importance of environment-dependent hydrogen bond   interactions in modeling protein folding. The developed approach   can be used for accurate and rapid sampling of conformational   spaces of proteins and protein-protein complexes and applied to   protein engineering and design of protein-protein   interactions.

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