Temperature weighted histogram analysis method, replica exchange, and transition paths
Temperature weighted histogram analysis method, replica exchange, and transition paths
复制标题
DOI：
10.1021/jp045294f
复制
发表时间：
2005-04-14
影响因子：
3.3
通讯作者：
Levy, RM
中科院分区：
文献类型：
--
作者：
Gallicchio, E;Andrec, M;Levy, RM
我们使用加权直方图分析方法分析来自副本交换分子动力学模拟的数据，以联合收割机来自所有温度副本（T-WHAM）的数据，从而获得G肽（蛋白G的B1结构域的C-末端β-发夹）在构象空间区域中的平均力的室温势，该构象空间区域未在室温下采样。我们能够确定在次要α-螺旋群体和主要β-发夹群体之间的过渡区域中的平均力的潜力，并确定它们之间的可能过渡路径，沿着该路径肽保留了大量的二级结构。这一观察结果为蛋白质中β折叠二级结构形成的可能机制提供了新的见解。我们开发了一种新的贝叶斯统计不确定性估计方法的任何数量来自WHAM，并用它来验证计算的潜力的平均力。通过对副本交换模拟的T-WHAM分析，在室温下估计具有不利自由能的平均力的潜力区域的可行性在可以解析地解决的系统上进一步测试，并提出了在更复杂的化学系统中发现的一些相同的挑战。
We analyzed the data from a replica exchange molecular dynamics simulation using the weighted histogram analysis method to combine data from all of the temperature replicas (T-WHAM) to obtain the room-temperature potential of mean force of the G-peptide (the C-terminal beta-hairpin of the B1 domain of protein G) in regions of conformational space not sampled at room temperature. We were able to determine the potential of mean force in the transition region between a minor a-helical population and the major beta-hairpin population and identify a possible transition path between them along which the peptide retains a significant amount of secondary structure. This observation provides new insights into a possible mechanism of formation of beta-sheet secondary structures in proteins. We developed a novel Bayesian statistical uncertainty estimation method for any quantity derived from WHAM and used it to validate the calculated potential of mean force. The feasibility of estimating regions of the potential of mean force with unfavorable free energy at room temperature by T-WHAM analysis of replica exchange simulations was further tested on a system that can be solved analytically and presented some of the same challenges found in more complex chemical systems.