Zhang Bin W, Jasnow David, Zuckerman Daniel M
Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18043-8. doi: 10.1073/pnas.0706349104. Epub 2007 Nov 1.
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.
对蛋白质中罕见的、大规模的构象转变进行计算抽样是一项公认的挑战——针对这一挑战，人们已经提出了许多具有潜在高效性的路径抽样方法。在这里，我们使用休伯和金的“加权系综”（WE）方法，研究钙调蛋白统一残基模型中的大规模转变。由于该模型相对简单，我们能够将我们的结果与强力模拟进行比较。比较表明，通过考虑（i）反应速率、（ii）事件持续时间的分布以及（iii）描述路径异质性的结构分布来评估，WE方法定量地再现了强力模拟的结果。重要的是，WE方法很容易应用于化学上更精确的模型，并且通过研究一系列较低温度，我们的结果表明，在更具挑战性的系统中，WE方法可以将效率提高几个数量级。
