論文

査読有り
2019年9月10日

Nontargeted Parallel Cascade Selection Molecular Dynamics Using Time-Localized Prediction of Conformational Transitions in Protein Dynamics

Journal of Chemical Theory and Computation
  • Ryuhei Harada
  • ,
  • Vladimir Sladek
  • ,
  • Yasuteru Shigeta

15
9
開始ページ
5144
終了ページ
5153
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1021/acs.jctc.9b00489
出版者・発行元
AMER CHEMICAL SOC

Copyright © 2019 American Chemical Society. Nontargeted parallel cascade selection molecular dynamics (nt-PaCS-MD) is an enhanced conformational sampling method of proteins, which does not rely on knowledge of the target structure. It makes use of cyclic resampling from some relevant initial structures to expand the searched conformational subspace. The efficiency of nt-PaCS-MD depends on the selections of these initial structures. They are usually stochastically occurring perturbed structures at which larger conformation transitions are about to happen. Reliable identification of these is the key to using nt-PaCS-MD. Two new parameters, the moving root-mean-square deviation (mRMSD) and the inner products of the backbone dihedral angles φ and ψ, are introduced as indicators of conformational outliers in MD trajectories. Both are based on the analysis of a time-localized set of coordinates, overcoming the need for a target structure while still capturing the complexity of the conformational transition. The reference to which the mRMSD relates is the close surrounding of the i-th conformation, often the (i-1)st one. Hence the name "time-localized" analysis. In this work, we focus on its interplay with nt-PaCS-MD and show that it increases its effectiveness compared to older versions. The target system is the midsized protein T4 lysozyme (in explicit water) on which we demonstrate the open-closed transition without referring to any target configuration. Additionally, we show that the short MD trajectories can be used for the construction of a free energy landscape of the conformational transition based on the Markov state model.

リンク情報
DOI
https://doi.org/10.1021/acs.jctc.9b00489
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31411882
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000485829800036&DestApp=WOS_CPL
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85071995552&origin=inward
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85071995552&origin=inward
ID情報
  • DOI : 10.1021/acs.jctc.9b00489
  • ISSN : 1549-9618
  • eISSN : 1549-9626
  • PubMed ID : 31411882
  • SCOPUS ID : 85071995552
  • Web of Science ID : WOS:000485829800036

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