Mimicking the action of folding chaperones by Hamiltonian replica-exchange molecular dynamics simulations: Application in the refinement of de novo models

Fan, Hao, Periole, Xavier and Mark, Alan E. (2012) Mimicking the action of folding chaperones by Hamiltonian replica-exchange molecular dynamics simulations: Application in the refinement of de novo models. Proteins: Structure, Function, and Bioinformatics, 80 7: 1744-1754. doi:10.1002/prot.24068


Author Fan, Hao
Periole, Xavier
Mark, Alan E.
Title Mimicking the action of folding chaperones by Hamiltonian replica-exchange molecular dynamics simulations: Application in the refinement of de novo models
Journal name Proteins: Structure, Function, and Bioinformatics   Check publisher's open access policy
ISSN 0887-3585
1097-0134
Publication date 2012-07-01
Year available 2012
Sub-type Article (original research)
DOI 10.1002/prot.24068
Open Access Status Not yet assessed
Volume 80
Issue 7
Start page 1744
End page 1754
Total pages 11
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley & Sons
Language eng
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.
Keyword Protein structure prediction
Protein structure refinement
Replica-exchange molecular dynamics
Chaperone
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP0878608
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 28 Jun 2012, 21:11:45 EST by Lucy O'Brien on behalf of School of Chemistry & Molecular Biosciences