The computer simulation of many molecular processes is complicated by long time scales caused by rare transitions between long-lived states. Here, we propose a new approach to simulate such rare events, which combines transition path sampling with enhanced exploration of configuration space. The method relies on exchange moves between configuration and trajectory space, carried out based on a generalized ensemble. This scheme substantially enhances the efficiency of the transition path sampling simulations, particularly for systems with multiple transition channels, and yields information on thermodynamics, kinetics and reaction coordinates of molecular processes without distorting their dynamics. The method is illustrated using the isomerization of proline in the KPTP tetrapeptide.

翻译：许多分子过程的计算机模拟因长寿命状态之间的罕见跃迁所导致的长时间尺度而变得复杂。本文提出一种模拟此类罕见事件的新方法，该方法将跃迁路径采样与构型空间增强探索相结合。该技术基于广义系综，通过构型空间与轨迹空间之间的交换移动实现。这一方案显著提升了跃迁路径采样模拟的效率，尤其适用于含有多条跃迁通道的系统，并能在不扭曲动力学的前提下提供分子过程的热力学、动力学及反应坐标信息。该方法通过KPTP四肽中脯氨酸的异构化反应加以验证。