WExplore: hierarchical exploration of high-dimensional spaces using the weighted ensemble algorithm.
WExplore: hierarchical exploration of high-dimensional spaces using the weighted ensemble algorithm.
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DOI：
10.1021/jp411479c
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发表时间：
2014-04-03
期刊：
影响因子：
--
通讯作者：
Brooks CL 3rd
中科院分区：
文献类型：
--
作者：
Dickson A;Brooks CL 3rd
由于生物分子系统中的大多数相关运动无法通过传统的分子动力学模拟进行，因此增强罕见事件采样的算法是必不可少的。人们对本质上无序的系统越来越感兴趣，并且希望在药物开发中瞄准蛋白质构象集合（而不是单一结构），这激发了对增强采样算法的需求，这些算法不仅限于“双盆”问题，而且可以有效地确定结构集合。对于没有经过充分研究的系统，这通常必须在很少或根本没有有关感兴趣动态的信息的情况下完成。在这里，我们提出了一种新颖的策略来确定结构集成，该策略使用在分层框架中组织的动态定义的采样区域。它基于加权集成算法，其中系统副本（“副本”）的集成通过合并和克隆操作定向到配置空间的新区域。采样层次结构允许定义大量区域，同时仅使用少量可以在多个长度尺度上平衡的副本。我们在两个可分析求解的模型系统上演示了该算法，并在显式溶剂中检查了 10 残基肽 chignolin。使用构型空间网络对后一个系统进行分析，发现有利于折叠的新型氢键。
As most relevant motions in biomolecular systems are inaccessible to conventional molecular dynamics simulations, algorithms that enhance sampling of rare events are indispensable. Increasing interest in intrinsically disordered systems and the desire to target ensembles of protein conformations (rather than single structures) in drug development motivate the need for enhanced sampling algorithms that are not limited to “two-basin” problems, and can efficiently determine structural ensembles. For systems that are not well-studied, this must often be done with little or no information about the dynamics of interest. Here we present a novel strategy to determine structural ensembles that uses dynamically defined sampling regions that are organized in a hierarchical framework. It is based on the weighted ensemble algorithm, where an ensemble of copies of the system (“replicas”) is directed to new regions of configuration space through merging and cloning operations. The sampling hierarchy allows for a large number of regions to be defined, while using only a small number of replicas that can be balanced over multiple length scales. We demonstrate this algorithm on two model systems that are analytically solvable and examine the 10-residue peptide chignolin in explicit solvent. The latter system is analyzed using a configuration space network and novel hydrogen bonds are found that facilitate folding.
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