Title: Capacities and the Free Passage of Entropic Barriers Show Chinese title

Title: 容量和熵势垒的自由通过

Abstract: We propose an approach for estimating the probability that a given small target, among many, will be the first to be reached in a molecular dynamics simulation. Reaching small targets out of a vast number of possible configurations constitutes an entropic barrier. Experimental evidence suggests that entropic barriers are ubiquitous in biomolecular systems, and often characterize the rate-limiting step of biomolecular processes. Presumably for the same reasons, they often characterize the rate-limiting step in simulations. To the extent that first-passage probabilities can be computed without requiring direct simulation, the process of traversing entropic barriers can replaced by a single choice from the computed ("first-passage") distribution. We will show that in the presence of certain entropic barriers, first-passage probabilities are approximately invariant to the initial configuration, provided that it is modestly far away from each of the targets. We will further show that as a consequence of this invariance, the first-passage distribution can be well-approximated in terms of "capacities" of local sets around the targets. Using these theoretical results and a Monte Carlo mechanism for approximating capacities, we provide a method for estimating the hitting probabilities of small targets in the presence of entropic barriers. In numerical experiments with an idealized ("golf-course") potential, the estimates are as accurate as the results of direct simulations, but far faster to compute. Show Chinese abstract

Abstract: 我们提出一种方法，用于估计在分子动力学模拟中，众多小目标中某个给定小目标首先被达到的概率。 在大量可能构型中达到小目标构成了熵障碍。 实验证据表明，熵障碍在生物分子系统中普遍存在，并且通常表征生物分子过程的限速步骤。 出于同样的原因，它们通常也表征模拟中的限速步骤。 只要可以无需直接模拟即可计算首次通过概率，那么穿越熵障碍的过程就可以由从计算出的（“首次通过”）分布中进行一次选择来替代。 我们将证明，在某些熵障碍存在的情况下，只要初始构型离每个目标都适度远离，首次通过概率近似不变。 我们还将进一步证明，由于这种不变性，首次通过分布可以用目标周围局部集合的“容量”很好地近似。 利用这些理论结果和一种用于近似容量的蒙特卡洛机制，我们提供了一种在存在熵障碍的情况下估计小目标击中概率的方法。 在具有理想化（“高尔夫球场”）势能的数值实验中，该估计结果的准确性与直接模拟的结果相当，但计算速度要快得多。