Ray Dhiman, Parrinello Michele
Atomistic Simulations, Italian Institute of Technology, Via Enrico Melen 83, 16152 Genova, Italy.
J Chem Theory Comput. 2023 Sep 12;19(17):5649-5670. doi: 10.1021/acs.jctc.3c00660. Epub 2023 Aug 16.
Metadynamics is a popular enhanced sampling algorithm for computing the free energy landscape of rare events by using molecular dynamics simulation. Ten years ago, Tiwary and Parrinello introduced the infrequent metadynamics approach for calculating the kinetics of transitions across free energy barriers. Since then, metadynamics-based methods for obtaining rate constants have attracted significant attention in computational molecular science. Such methods have been applied to study a wide range of problems, including protein-ligand binding, protein folding, conformational transitions, chemical reactions, catalysis, and nucleation. Here, we review the principles of elucidating kinetics from metadynamics-like approaches, subsequent methodological developments in this area, and successful applications on chemical, biological, and material systems. We also highlight the challenges of reconstructing accurate kinetics from enhanced sampling simulations and the scope of future developments.
元动力学是一种流行的增强采样算法，用于通过分子动力学模拟计算罕见事件的自由能景观。十年前，蒂瓦里和帕里尼罗引入了非频繁元动力学方法来计算跨越自由能垒的跃迁动力学。从那时起，基于元动力学的获取速率常数的方法在计算分子科学中引起了广泛关注。此类方法已被应用于研究广泛的问题，包括蛋白质-配体结合、蛋白质折叠、构象转变、化学反应、催化和成核。在此，我们回顾了从类元动力学方法阐明动力学的原理、该领域随后的方法学发展以及在化学、生物和材料系统上的成功应用。我们还强调了从增强采样模拟中重建准确动力学的挑战以及未来发展的范围。
