Iida Shinji, Tomoshi Kameda
Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-Ku, Tokyo, 135-0064 Japan.
Biophys Rev. 2022 Dec 29;14(6):1303-1314. doi: 10.1007/s12551-022-01036-3. eCollection 2022 Dec.
Non-equilibrium molecular dynamics (NEMD) simulation has been recognized as a powerful tool for examining biomolecules and provides fruitful insights into not only non-equilibrium but also equilibrium processes. We review recent advances in NEMD simulation and relevant, fundamental results of non-equilibrium statistical mechanics. We first introduce Crooks fluctuation theorem and Jarzynski equality that relate free energy difference to work done on a physical system during a non-equilibrium process. The theorems are beneficial for the analysis of NEMD trajectories. We then describe rate theory, a framework to calculate molecular kinetics from a non-equilibrium process; this theoretical framework enables us to calculate a reaction time-mean-first passage time-from NEMD trajectories. We, in turn, present recent NEMD techniques that apply an external force to a system to enhance molecular dissociation and introduce their application to biomolecules. Lastly, we show the current status of an appropriate selection of reaction coordinates for NEMD simulation.
非平衡分子动力学（NEMD）模拟已被公认为是研究生物分子的强大工具，它不仅为非平衡过程，也为平衡过程提供了丰富的见解。我们回顾了NEMD模拟的最新进展以及非平衡统计力学的相关基础结果。我们首先介绍将自由能差与非平衡过程中对物理系统所做的功联系起来的克鲁克斯涨落定理和雅尔津斯基等式。这些定理有助于分析NEMD轨迹。然后我们描述速率理论，这是一个从非平衡过程计算分子动力学的框架；这个理论框架使我们能够从NEMD轨迹计算反应时间平均首次通过时间。接着，我们介绍了最近的NEMD技术，这些技术对系统施加外力以增强分子解离，并介绍了它们在生物分子中的应用。最后，我们展示了为NEMD模拟适当选择反应坐标的现状。
