Dipartimento di Chimica, Università di Firenze, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Italy.
Dipartimento di Scienze Chimiche, Università di Padova, Via Marzolo 1, I-35131 Padova, Italy.
J Chem Theory Comput. 2011 Mar 8;7(3):582-93. doi: 10.1021/ct100568n. Epub 2011 Feb 9.
To achieve acceptable accuracy in fast-switching free energy estimates by Jarzynski equality [ Phys. Rev. Lett. 1997 , 78 , 2690 ] or Crooks fluctuation theorem [ J. Stat. Phys. 1998 , 90 , 1481 ], it is often necessary to realize a large number of externally driven trajectories. This is basically due to inefficient calculation of path-ensemble averages arising from the work dissipated during the nonequilibrium paths. We propose a computational technique, addressed to Monte Carlo simulations, to improve free energy estimates by lowering the dissipated work. The method is inspired by the dynamical freezing approach, recently developed in the context of molecular dynamics simulations [ Phys. Rev. E 2009 , 80 , 041124 ]. The idea is to limit the configurational sampling to particles of a well-established region of the sample (namely, the region where dissipation is supposed to occur), while leaving fixed (frozen) the other particles. Therefore, the method, called configurational freezing, is based on the reasonable assumption that dissipation is a local phenomenon in single-molecule nonequilibrium processes, a statement which is satisfied by most processes, including folding of biopolymers, molecular docking, alchemical transformations, etc. At variance with standard simulations, in configurational freezing simulations the computational cost is not correlated with the size of the whole system, but rather with that of the reaction site. The method is illustrated in two examples, i.e., the calculation of the water to methane relative hydration free energy and the calculation of the potential of mean force of two methane molecules in water solution as a function of their distance.
为了在快速切换自由能估计中实现可接受的准确性，例如通过 Jarzynski 等式[Phys. Rev. Lett. 1997, 78, 2690]或 Crooks 涨落定理[J. Stat. Phys. 1998, 90, 1481]，通常需要实现大量外部驱动轨迹。这主要是由于在非平衡路径中耗散的功导致路径集合平均值的计算效率低下。我们提出了一种计算技术，针对蒙特卡罗模拟，通过降低耗散功来提高自由能估计。该方法的灵感来自最近在分子动力学模拟背景下开发的动力学冻结方法[Phys. Rev. E 2009, 80, 041124]。该方法的基本思想是将构象采样限制在样本中一个已建立的区域（即耗散应该发生的区域）的粒子上，同时固定（冻结）其他粒子。因此，该方法称为构象冻结，它基于一个合理的假设，即耗散是单分子非平衡过程中的局部现象，这一说法适用于大多数过程，包括生物聚合物折叠、分子对接、化学转变等。与标准模拟不同，在构象冻结模拟中，计算成本与整个系统的大小无关，而是与反应部位的大小相关。该方法在两个示例中进行了说明，即计算水到甲烷的相对水合自由能和计算两个甲烷分子在水溶液中的平均力势能作为它们距离的函数。
