Efficient and verified simulation of a path ensemble for conformational change in a united-residue model of calmodulin

Bin W. Zhang, David Jasnow, Daniel M. Zuckerman

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

The computational sampling of rare, large-scale, conformational transitions in proteins is a well appreciated challenge - for which a number of potentially efficient path-sampling methodologies have been proposed. Here, we study a large-scale transition in a united-residue model of calmodulin using the "weighted ensemble" (WE) approach of Huber and Kim. Because of the model's relative simplicity, we are able to compare our results with brute-force simulations. The comparison indicates that the WE approach quantitatively reproduces the brute-force results, as assessed by considering (i) the reaction rate, (ii) the distribution of event durations, and (iii) structural distributions describing the heterogeneity of the paths. Importantly, the WE method is readily applied to more chemically accurate models, and by studying a series of lower temperatures, our results suggest that the WE method can increase efficiency by orders of magnitude in more challenging systems.

Original languageEnglish (US)
Pages (from-to)18043-18048
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number46
DOIs
StatePublished - Nov 13 2007

Keywords

  • Conformational transition
  • Path sampling
  • Transition path
  • Weighted ensemble

ASJC Scopus subject areas

  • General

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