SGOOP-d: Estimating Kinetic Distances and Reaction Coordinate Dimensionality for Rare Event Systems from Biased/Unbiased Simulations
SGOOP-d: Estimating Kinetic Distances and Reaction Coordinate Dimensionality for Rare Event Systems from Biased/Unbiased Simulations
复制标题
SGOOP-d：通过有偏/无偏模拟估计罕见事件系统的动力学距离和反应坐标维数
DOI：
10.1021/acs.jctc.1c00431
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Tiwary, Pratyush
中科院分区：
文献类型：
--
作者：
Tsai, Sun-Ting;Smith, Zachary;Tiwary, Pratyush
理解动力学包括反应途径和相关的过渡速率是许多化学和生物系统中的重要而困难的问题，特别是在多个竞争途径的情况下。当这些高维系统被投影到低维坐标上时，通常需要增强采样或解释模拟和实验，最终可能会失去底层高维景观的动力学连通性。因此，在低维投影中，亚稳态可能看起来比实际更近或更远。为了解决这个问题，在这项工作中，我们开发了一种形式主义，学习一个多维但最小复杂的反应坐标（RC）的通用高维系统。当沿着该RC沿着投影时，所有可能的动力学相关路径都可以被划分，并且保持真正的高维连通性。我们的方法的定义属性之一在于，它可以工作在长期无偏模拟以及偏模拟经常需要罕见的事件系统。我们通过研究包括小肽Ace-Ala 3-Nme中的构象转变的一系列模型系统来证明该方法的实用性，其中我们示出了如何通过我们先前公开的光谱间隙优化方法“SGOP”[Tivary，P.和Berne，B. J.Proc. Natl. Acad. Sci.2016，113，2839]可以分别捕获28个主要状态到状态转变中的23个和所有28个的动力学。
Understanding kinetics including reaction pathways and associated transition rates is an important yet difficult problem in numerous chemical and biological systems, especially in situations with multiple competing pathways. When these high-dimensional systems are projected on low-dimensional coordinates, which are often needed for enhanced sampling or for interpretation of simulations and experiments, one can end up losing the kinetic connectivity of the underlying high-dimensional landscape. Thus, in the low-dimensional projection, metastable states might appear closer or further than they actually are. To deal with this issue, in this work, we develop a formalism that learns a multidimensional yet minimally complex reaction coordinate (RC) for generic high-dimensional systems. When projected along this RC, all possible kinetically relevant pathways can be demarcated and the true high-dimensional connectivity is maintained. One of the defining attributes of our method lies in that it can work on long unbiased simulations as well as biased simulations often needed for rare event systems. We demonstrate the utility of the method by studying a range of model systems including conformational transitions in a small peptide Ace-Ala3-Nme, where we show how two-dimensional and three-dimensional RCs found by our previously published spectral gap optimization method “SGOOP” [Tiwary, P. and Berne, B. J.Proc. Natl. Acad. Sci.2016,113, 2839] can capture the kinetics for 23 and all 28 out of the 28 dominant state-to-state transitions, respectively.