A Simple and Accurate Method To Calculate Free Energy Profiles and Reaction Rates from Restrained Molecular Simulations of Diffusive Processes.
A Simple and Accurate Method To Calculate Free Energy Profiles and Reaction Rates from Restrained Molecular Simulations of Diffusive Processes.
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一种通过扩散过程的约束分子模拟计算自由能分布和反应速率的简单而准确的方法。
DOI：
10.1021/acs.jpcb.6b02139
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Karplus,Martin
中科院分区：
文献类型：
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作者：
Ovchinnikov,Victor;Nam,Kwangho;Karplus,Martin
本文提出了一种从限制分子模拟中同时获得扩散体系自由能分布和扩散常数的方法。该方法是基于低阶展开的自由能和扩散系数的反应坐标的函数。这些扩展导致模拟统计和模型参数之间的简单分析关系。该方法进行了测试的1D和2D模型系统，其精度被发现是可比的或优于现有的替代品，这是简要讨论。该方法的一个重要方面是自由能是通过积分其导数来构造的，其可以在不需要重叠采样窗口的情况下计算。该方法在任何支持外部伞电位的分子模拟程序中的实施（例如，CHARMM）只需要修改几行代码。作为对实际生物分子体系的适用性的证明，该方法被应用于模拟隐式溶剂中16残基肽的α-螺旋Participate β-折叠转变，反应坐标由弦方法提供。简要讨论了该方法的可能修改;它们包括推广到多维反应坐标[在Ermak和McCammon（Ermak，D. L.的; McCammon，J.A.J.Chem.Phys.1978，69，1352-1360）]，自由能表面的高阶展开，在非平衡系统中的适用性，以及Markovianity的简单检验。鉴于该方法相对于标准伞形采样的开销较小，我们建议在伞形电位模拟合适的情况下将其常规应用。
A method is developed to obtain simultaneously free energy profiles and diffusion constants from restrained molecular simulations in diffusive systems. The method is based on low-order expansions of the free energy and diffusivity as functions of the reaction coordinate. These expansions lead to simple analytical relationships between simulation statistics and model parameters. The method is tested on 1D and 2D model systems; its accuracy is found to be comparable to or better than that of the existing alternatives, which are briefly discussed. An important aspect of the method is that the free energy is constructed by integrating its derivatives, which can be computed without need for overlapping sampling windows. The implementation of the method in any molecular simulation program that supports external umbrella potentials (e.g., CHARMM) requires modification of only a few lines of code. As a demonstration of its applicability to realistic biomolecular systems, the method is applied to model the α-helix ↔ β-sheet transition in a 16-residue peptide in implicit solvent, with the reaction coordinate provided by the string method. Possible modifications of the method are briefly discussed; they include generalization to multidimensional reaction coordinates [in the spirit of the model of Ermak and McCammon (Ermak, D. L.; McCammon, J. A.J. Chem. Phys.1978,69, 1352–1360)], a higher-order expansion of the free energy surface, applicability in nonequilibrium systems, and a simple test for Markovianity. In view of the small overhead of the method relative to standard umbrella sampling, we suggest its routine application in the cases where umbrella potential simulations are appropriate.