Solvent interaction energy calculations on molecular dynamics trajectories: increasing the efficiency using systematic frame selection.
Solvent interaction energy calculations on molecular dynamics trajectories: increasing the efficiency using systematic frame selection.
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DOI：
10.1021/ci200191m
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发表时间：
2011-10-24
影响因子：
5.6
通讯作者：
Thompson JJ
中科院分区：
文献类型：
--
作者：
Lill MA;Thompson JJ
端点方法，如线性相互作用能(LIE)分析、分子力学广义Born溶剂可及表面(MM/GBSA)和溶剂相互作用能(SIE)分析已成为计算蛋白质-配体结合自由能的流行方法。这种方法通常使用分子动力学(MD)模拟来生成包含结合和非结合状态的蛋白质结构集合。能量评估方法(LIE，MM/GBSA或SIE)随后被用来计算系综中每个成员的能量，从而提供束缚态和非束缚态之间的平均自由能差的估计。需要为每个帧和每个轨迹同时进行MD模拟和能量计算的工作流程被证明是计算昂贵的。为了降低与端点方法相关的高计算成本，我们研究了几种可以从MD模拟中智能地选择帧的方法，包括聚类，并解决了选择的帧的数量如何影响SIE计算的精度的问题。
End-point methods such as Linear Interaction Energy (LIE) analysis, Molecular Mechanics Generalized Born Solvent Accessible Surface (MM/GBSA) and Solvent Interaction Energy (SIE) analysis have become popular techniques to calculate the free energy associated with protein-ligand binding. Such methods typically use molecular dynamics (MD) simulations to generate an ensemble of protein structures that encompasses the bound and unbound states. The energy evaluation method (LIE, MM/GBSA or SIE) is subsequently used to calculate the energy of each member of the ensemble, thus providing an estimate of the average free energy difference between the bound and unbound states. The workflow requiring both MD simulation and energy calculation for each frame and each trajectory proves to be computationally expensive. In an attempt to reduce the high computational cost associated with end-point methods, we study several methods by which frames may be intelligently selected from the MD simulation including clustering and address the question how the number of selected frames influences the accuracy of the SIE calculations.