Molecular Dynamics–Based Thermodynamic and Kinetic Characterization of Membrane Protein Conformational Transitions
Molecular Dynamics–Based Thermodynamic and Kinetic Characterization of Membrane Protein Conformational Transitions
复制标题
基于分子动力学的膜蛋白构象转变的热力学和动力学表征
DOI：
10.1007/978-1-0716-1394-8_16
复制
发表时间：
2021
影响因子：
--
通讯作者：
Moradi, Mahmoud
中科院分区：
文献类型：
--
作者：
Ogden, Dylan;Moradi, Mahmoud
分子动力学(MD)模拟是研究膜蛋白结构动力学的常规方法。然而，传统的分子生物学方法往往无法提取膜蛋白的重要构象转变，如参与主动膜转运或通道激活过程的蛋白。在这里，我们描述了多种基于分子动力学的技术的组合，这些技术允许对膜蛋白的大规模构象变化的能量学和动力学进行严格的表征。该方法基于有偏的、非平衡的、基于集体变量的模拟，包括非平衡拉动、具有成群轨迹的弦方法、偏差交换伞形抽样和速率估计技术。
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.