Conformational populations of ligand-sized molecules by replica exchange molecular dynamics and temperature reweighting.
Conformational populations of ligand-sized molecules by replica exchange molecular dynamics and temperature reweighting.
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DOI：
10.1002/jcc.21419
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发表时间：
2010-05
影响因子：
3
通讯作者：
Levy, Ronald M.
中科院分区：
文献类型：
--
作者：
Okumura, Hisashi;Gallicchio, Emilio;Levy, Ronald M.
关键词：
利用复制交换（RE）分子动力学（MD）方法有效地估计配体大小的分子在溶液中的构象群体的影响。我们比较了一系列烷烃和利匹韦林（TMC 278），对HIV-1逆转录酶的抑制剂，与隐式溶剂化的并行RE分子动力学方法的传统恒温MD技术的计算效率。我们发现，构象人口准确估计这两种方法，但副本交换估计收敛速度更快，特别是利匹韦林的特点是多个稳定状态分离的高自由能障碍。此外，收敛性增强时，加权直方图分析方法（WHAM）估计人口从多个RE温度副本收集的数据。对于小的药物样分子的能量屏障分离的稳定状态，使用RE与WHAM是一种有效的计算方法，用于估计的贡献配体构象重组的结合亲和力。
The use of the replica exchange (RE) molecular dynamics (MD) method for the efficient estimation of conformational populations of ligand-sized molecules in solution is investigated. We compare the computational efficiency of the traditional constant temperature MD technique to that of the parallel RE molecular dynamics method for a series of alkanes and rilpivirine (TMC278), an inhibitor against HIV-1 reverse transcriptase, with implicit solvation. We show that conformational populations are accurately estimated by both methods, however replica exchange estimates converge at a faster rate especially for rilpivirine which is characterized by multiple stable states separated by high free energy barriers. Furthermore convergence is enhanced when the weighted histogram analysis method (WHAM) is employed to estimate populations from the data collected from multiple RE temperature replicas. For small drug-like molecules with energetic barriers separating the stable states, the use of RE with WHAM is an efficient computational approach for estimating the contribution of ligand conformational reorganization to binding affinities.
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影响因子：
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