发表机构
Norwegian University of Science and Technology（挪威科技大学）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
本文提出多分辨率线栅栏法，通过高分辨率传播子轨迹增加射击点扩散，提升路径采样效率，在蛋白质-配体解离中实现超一个数量级的加速。
AI 中文摘要
路径采样方法通过蒙特卡洛（MC）移动计算热力学和动力学性质，这些移动从短的向前和向后分子动力学（MD）片段生成轨迹。最近，线栅栏移动被开发出来，以实现接近统一的接受率，同时快速去相关连续路径，这两个性质在传统MC方案中通常是相互冲突的。然而，在大型系统（如生物分子模拟）中，帧保存频率通常保持较低以减少存储需求。同样，当评估序参数昂贵时，帧保存频率降低以减少相关成本。在任一情况下，这都可能严重限制可用射击点的数量，在极端情况下仅留下一个点（通常是具有最高序参数值的点）可供射击。重复射击可能源自相同构型，从而降低采样效率。在此，我们引入线栅栏移动的多分辨率变体，其中选定的子轨迹以比存储轨迹更高的时间分辨率传播。这种细化仅影响MC移动，不改变生成路径的结构或存储，但增强了射击点沿轨迹的扩散，从而提高采样效率。该方法在两个模型系统和一个真实的蛋白质-配体解离过程中得到展示，后者显示估计效率提升超过一个数量级。
英文摘要
Path sampling methods enable the computation of thermodynamic and kinetic properties through Monte Carlo (MC) moves that generate trajectories from short forward and backward molecular dynamics (MD) segments. Recently, the wire-fencing move was developed to achieve near-unity acceptance while also rapidly decorrelating successive paths, two properties that are usually in conflict in conventional MC schemes. However, in large systems, such as biomolecular simulations, the frame-saving frequency is often kept low to reduce storage requirements. Likewise, when evaluating the order parameter is expensive, frames are saved less frequently to reduce the associated cost. In either situation, this can severely limit the number of available shooting points, in extreme situations leaving only a single point, typically the one with the highest order parameter value, accessible for shooting. Repeated shootings may then originate from the same configuration, reducing sampling efficiency. Here, we introduce a multi-resolution variant of the wire-fencing move in which selected subtrajectories are propagated at higher temporal resolution than the stored trajectories. This refinement affects only the MC move and does not alter the structure or storage of the generated paths, but enhances the diffusion of shooting points along the trajectory and thereby improves sampling efficiency. The approach is demonstrated on two model systems and a realistic protein--ligand unbinding process, with the latter showing an estimated efficiency improvement of more than an order of magnitude.
Comments13 pages, 4 figures
