TY - JOUR
T1 - Efficient and verified simulation of a path ensemble for conformational change in a united-residue model of calmodulin
AU - Zhang, Bin W.
AU - Jasnow, David
AU - Zuckerman, Daniel M.
PY - 2007/11/13
Y1 - 2007/11/13
N2 - 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.
AB - 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.
KW - Conformational transition
KW - Path sampling
KW - Transition path
KW - Weighted ensemble
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U2 - 10.1073/pnas.0706349104
DO - 10.1073/pnas.0706349104
M3 - Article
C2 - 17984047
AN - SCOPUS:36749060078
SN - 0027-8424
VL - 104
SP - 18043
EP - 18048
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 46
ER -