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Mimicking the action of folding chaperones by Hamiltonian replica‐exchange molecular dynamics simulations: Application in the refinement of de novo models
Author(s) -
Fan Hao,
Periole Xavier,
Mark Alan E.
Publication year - 2012
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24068
Subject(s) - replica , molecular dynamics , protein folding , chemistry , folding (dsp implementation) , in silico , protein secondary structure , biological system , computational chemistry , statistical physics , physics , biology , art , biochemistry , electrical engineering , visual arts , engineering , gene
Abstract The efficiency of using a variant of Hamiltonian replica‐exchange molecular dynamics (Chaperone H‐replica‐exchange molecular dynamics [CH‐REMD]) for the refinement of protein structural models generated de novo is investigated. In CH‐REMD, the interaction between the protein and its environment, specifically, the electrostatic interaction between the protein and the solvating water, is varied leading to cycles of partial unfolding and refolding mimicking some aspects of folding chaperones. In 10 of the 15 cases examined, the CH‐REMD approach sampled structures in which the root‐mean‐square deviation (RMSD) of secondary structure elements (SSE‐RMSD) with respect to the experimental structure was more than 1.0 Å lower than the initial de novo model. In 14 of the 15 cases, the improvement was more than 0.5 Å. The ability of three different statistical potentials to identify near‐native conformations was also examined. Little correlation between the SSE‐RMSD of the sampled structures with respect to the experimental structure and any of the scoring functions tested was found. The most effective scoring function tested was the DFIRE potential. Using the DFIRE potential, the SSE‐RMSD of the best scoring structures was on average 0.3 Å lower than the initial model. Overall the work demonstrates that targeted enhanced‐sampling techniques such as CH‐REMD can lead to the systematic refinement of protein structural models generated de novo but that improved potentials for the identification of near‐native structures are still needed. Proteins 2012; © 2012 Wiley Periodicals, Inc.