论文标题
随机最佳控制分子过渡路径的集体可变自由采样
Stochastic Optimal Control for Collective Variable Free Sampling of Molecular Transition Paths
论文作者
论文摘要
我们考虑了在两个分子系统的两个给定的亚稳态态之间取样过渡路径的问题,例如化学反应的折叠和展开的蛋白质或产物和反应物。由于存在分离状态的高能屏障,因此不太可能通过标准分子动力学(MD)模拟对这些过渡路径进行采样。增加具有偏见潜力的MD的传统方法,以增加过渡的可能性,取决于基于集体变量(CVS)的降低性步骤。不幸的是,选择合适的简历需要化学直觉,因此传统方法并不总是适用于较大的系统。另外,当使用错误的CV时,偏差电位可能不会是最小的,并且沿着与过渡无关的系统偏置系统。我们提出了一种用于采样上述过渡的机器学习方法,显示了采样分子过渡路径的问题,Schrödinger桥问题和随机最佳控制之间的形式关系。与以前的非机械学习方法不同,我们的方法(名为PIPS)不取决于CVS。我们表明,我们的方法成功会产生低能量转变,用于丙氨酸二肽以及较大的聚丙烯和氯醇蛋白。
We consider the problem of sampling transition paths between two given metastable states of a molecular system, e.g. a folded and unfolded protein or products and reactants of a chemical reaction. Due to the existence of high energy barriers separating the states, these transition paths are unlikely to be sampled with standard Molecular Dynamics (MD) simulation. Traditional methods to augment MD with a bias potential to increase the probability of the transition rely on a dimensionality reduction step based on Collective Variables (CVs). Unfortunately, selecting appropriate CVs requires chemical intuition and traditional methods are therefore not always applicable to larger systems. Additionally, when incorrect CVs are used, the bias potential might not be minimal and bias the system along dimensions irrelevant to the transition. Showing a formal relation between the problem of sampling molecular transition paths, the Schrödinger bridge problem and stochastic optimal control with neural network policies, we propose a machine learning method for sampling said transitions. Unlike previous non-machine learning approaches our method, named PIPS, does not depend on CVs. We show that our method successful generates low energy transitions for Alanine Dipeptide as well as the larger Polyproline and Chignolin proteins.