Church Jonathan R, Blumer Ofir, Keidar Tommer D, Ploutno Leo, Reuveni Shlomi, Hirshberg Barak
School of Chemistry, Tel Aviv University, Tel Aviv 6997801, Israel.
The Center for Computational Molecular and Materials Science, Tel Aviv University, Tel Aviv 6997801, Israel.
J Chem Theory Comput. 2025 Jan 28;21(2):605-613. doi: 10.1021/acs.jctc.4c01238. Epub 2025 Jan 8.
We present a procedure for enhanced sampling of molecular dynamics simulations through informed stochastic resetting. Many phenomena, such as protein folding and crystal nucleation, occur over time scales inaccessible in standard simulations. We recently showed that stochastic resetting can accelerate molecular simulations that exhibit broad transition time distributions. However, standard stochastic resetting does not exploit any information about the reaction progress. For a model system and chignolin in explicit water, we demonstrate that an informed resetting protocol leads to greater accelerations than standard stochastic resetting in molecular dynamics and Metadynamics simulations. This is achieved by resetting only when a certain condition is met, e.g., when the distance from the target along the reaction coordinate is larger than some threshold. We use these accelerated simulations to infer important kinetic observables such as the unbiased mean first-passage time and direct transit time. For the latter, Metadynamics with informed resetting leads to speedups of 2-3 orders of magnitude over unbiased simulations with relative errors of only ∼35-70%. Our work significantly extends the applicability of stochastic resetting for enhanced sampling of molecular simulations.
我们提出了一种通过信息随机重置来增强分子动力学模拟采样的方法。许多现象，如蛋白质折叠和晶体成核，发生的时间尺度在标准模拟中是无法达到的。我们最近表明，随机重置可以加速那些呈现出宽泛过渡时间分布的分子模拟。然而，标准的随机重置并未利用任何有关反应进程的信息。对于一个模型系统以及在明确水环境中的奇诺林，我们证明在分子动力学和元动力学模拟中，一种信息重置协议比标准随机重置能带来更大的加速效果。这是通过仅在满足特定条件时进行重置来实现的，例如，当沿着反应坐标与目标的距离大于某个阈值时。我们使用这些加速模拟来推断重要的动力学可观测量，如无偏平均首次通过时间和直接穿越时间。对于后者，带有信息重置的元动力学比无偏模拟加速了2 - 3个数量级，相对误差仅约为35 - 70%。我们的工作显著扩展了随机重置在增强分子模拟采样方面的适用性。
