Yu Tang-Qing, Lu Jianfeng, Abrams Cameron F, Vanden-Eijnden Eric
Courant Institute of Mathematical Sciences, New York University, New York, NY 10012.
Department of Mathematics, Duke University, Durham, NC 27708; Department of Physics, Duke University, Durham, NC 27708; Department of Chemistry, Duke University, Durham, NC 27708.
Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11744-11749. doi: 10.1073/pnas.1605089113. Epub 2016 Oct 3.
Replica exchange molecular dynamics (REMD) is a popular method to accelerate conformational sampling of complex molecular systems. The idea is to run several replicas of the system in parallel at different temperatures that are swapped periodically. These swaps are typically attempted every few MD steps and accepted or rejected according to a Metropolis-Hastings criterion. This guarantees that the joint distribution of the composite system of replicas is the normalized sum of the symmetrized product of the canonical distributions of these replicas at the different temperatures. Here we propose a different implementation of REMD in which (i) the swaps obey a continuous-time Markov jump process implemented via Gillespie's stochastic simulation algorithm (SSA), which also samples exactly the aforementioned joint distribution and has the advantage of being rejection free, and (ii) this REMD-SSA is combined with the heterogeneous multiscale method to accelerate the rate of the swaps and reach the so-called infinite-swap limit that is known to optimize sampling efficiency. The method is easy to implement and can be trivially parallelized. Here we illustrate its accuracy and efficiency on the examples of alanine dipeptide in vacuum and C-terminal β-hairpin of protein G in explicit solvent. In this latter example, our results indicate that the landscape of the protein is a triple funnel with two folded structures and one misfolded structure that are stabilized by H-bonds.
复制交换分子动力学（REMD）是一种加速复杂分子系统构象采样的常用方法。其思路是在不同温度下并行运行系统的多个副本，并定期交换这些副本。这些交换通常每隔几步分子动力学步骤尝试一次，并根据Metropolis-Hastings准则接受或拒绝。这保证了副本复合系统的联合分布是这些副本在不同温度下的正则分布的对称化乘积的归一化总和。在这里，我们提出了一种不同的REMD实现方式，其中：（i）交换服从通过 Gillespie 随机模拟算法（SSA）实现的连续时间马尔可夫跳跃过程，该算法也能精确采样上述联合分布，并且具有无拒绝的优点；（ii）这种 REMD-SSA 与非均匀多尺度方法相结合，以加速交换速率并达到所谓的无限交换极限，已知该极限可优化采样效率。该方法易于实现且可轻松并行化。在这里，我们以真空中的丙氨酸二肽和明确溶剂中蛋白质 G 的 C 端β-发夹为例来说明其准确性和效率。在后一个例子中，我们的结果表明该蛋白质的构象是一个三漏斗结构，有两个折叠结构和一个由氢键稳定的错误折叠结构。
