Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
J Chem Phys. 2017 Jun 28;146(24):244113. doi: 10.1063/1.4989486.
The calculation of free energy differences is a crucial step in the characterization and understanding of the physical properties of biological molecules. In the development of efficient methods to compute these quantities, a promising strategy is that of employing a dual-resolution representation of the solvent, specifically using an accurate model in the proximity of a molecule of interest and a simplified description elsewhere. One such concurrent multi-resolution simulation method is the Adaptive Resolution Scheme (AdResS), in which particles smoothly change their resolution on-the-fly as they move between different subregions. Before using this approach in the context of free energy calculations, however, it is necessary to make sure that the dual-resolution treatment of the solvent does not cause undesired effects on the computed quantities. Here, we show how AdResS can be used to calculate solvation free energies of small polar solutes using Thermodynamic Integration (TI). We discuss how the potential-energy-based TI approach combines with the force-based AdResS methodology, in which no global Hamiltonian is defined. The AdResS free energy values agree with those calculated from fully atomistic simulations to within a fraction of kT. This is true even for small atomistic regions whose size is on the order of the correlation length, or when the properties of the coarse-grained region are extremely different from those of the atomistic region. These accurate free energy calculations are possible because AdResS allows the sampling of solvation shell configurations which are equivalent to those of fully atomistic simulations. The results of the present work thus demonstrate the viability of the use of adaptive resolution simulation methods to perform free energy calculations and pave the way for large-scale applications where a substantial computational gain can be attained.
自由能差异的计算是描述和理解生物分子物理性质的关键步骤。在开发计算这些量的有效方法时，一种有前途的策略是采用溶剂的双重分辨率表示，特别是在感兴趣的分子附近使用精确模型，而在其他地方使用简化描述。一种这样的并发多分辨率模拟方法是自适应分辨率方案 (AdResS)，其中粒子在不同子区域之间移动时平滑地改变其分辨率。然而，在将这种方法应用于自由能计算之前，有必要确保溶剂的双重分辨率处理不会对计算出的量产生不利影响。在这里，我们展示了如何使用自适应分辨率方案 (AdResS) 使用热力学积分 (TI) 计算小极性溶质的溶剂化自由能。我们讨论了基于势能的 TI 方法如何与基于力的 AdResS 方法相结合，在这种方法中没有定义全局哈密顿量。AdResS 的自由能值与完全原子模拟计算的自由能值相差不到 kT 的分数。即使对于大小与相关长度相当的小原子区域，或者当粗粒度区域的性质与原子区域的性质极其不同时，也是如此。这些准确的自由能计算之所以成为可能，是因为 AdResS 允许采样与完全原子模拟等效的溶剂化壳配置。因此，本工作的结果证明了使用自适应分辨率模拟方法进行自由能计算的可行性，并为可以获得大量计算收益的大规模应用铺平了道路。
