Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR, USA.
Methods Mol Biol. 2021;2302:289-309. doi: 10.1007/978-1-0716-1394-8_16.
Molecular dynamics (MD) simulations are routinely used to study structural dynamics of membrane proteins. However, conventional MD is often unable to sample functionally important conformational transitions of membrane proteins such as those involved in active membrane transport or channel activation process. Here we describe a combination of multiple MD based techniques that allows for a rigorous characterization of energetics and kinetics of large-scale conformational changes in membrane proteins. The methodology is based on biased, nonequilibrium, collective-variable based simulations including nonequilibrium pulling, string method with swarms of trajectories, bias-exchange umbrella sampling, and rate estimation techniques.
分子动力学（MD）模拟通常用于研究膜蛋白的结构动力学。然而，传统的 MD 通常无法采样膜蛋白的功能重要构象转变，例如那些涉及主动膜转运或通道激活过程的构象转变。在这里，我们描述了多种基于 MD 的技术的组合，这些技术可以严格表征膜蛋白中大规模构象变化的能量学和动力学。该方法基于有偏差的、非平衡的、基于集体变量的模拟，包括非平衡拉伸、带有轨迹群的字符串方法、偏差交换伞形采样和速率估计技术。
