Levy Ronald M, Matubayasi Nobuyuki, Zhang Bin W
Center for Biophysics and Computational Biology and Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, United States.
Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan.
J Phys Chem B. 2020 Dec 31;124(52):11771-11782. doi: 10.1021/acs.jpcb.0c08988. Epub 2020 Dec 11.
Solvation thermodynamics is concerned with the evaluation and physical interpretation of solvation free energies. Endpoints DFT provides a framework for computing solvation free energies by combining molecular simulations with a version of the classical density-functional theory of solutions which focuses on ω, the indirect (solvent-mediated) part of the solute-solvent potential of mean force (indirect PMF). The simulations are performed at the endpoints of a hypothetical charging process which transforms the solvent density from the pure liquid state to that of the solution state. The endpoints DFT expression for solvation free energy can be shown to be equivalent to the standard expression for which the key quantity is the direct correlation function, but it has the advantage that the indirect term ω is more focused on the change in solvent-solvent correlations with respect to the pure liquid as the solute is inserted into the solution. In this Perspective, we review recent developments of endpoints DFT, highlighting a series of papers we have written together beginning in 2017. We emphasize the importance of dimensionality reduction as the key to the evaluation of endpoints DFT expressions and present a recently developed, spatially resolved version of the theory. The role of interfacial water at certain positions which stabilize or destabilize a solute in solution can be analyzed with the spatially resolved version, and it is of considerable interest to investigate how changes in solvation affect protein-ligand binding and conformational landscapes from an endpoints DFT perspective. Endpoints DFT can also be employed in materials science; an example involving the rational design strategy for polymer membrane separation is described. The endpoints DFT method is a scheme to evaluate the solvation free energy by introducing approximations to integrate the classical density functional over a charging parameter. We have further proposed a new functional which captures the correct dependence of the indirect PMF ω at both endpoints of the charging process, and we review how it might be employed in future work.
溶剂化热力学关注溶剂化自由能的评估和物理解释。端点密度泛函理论（Endpoints DFT）通过将分子模拟与一种经典溶液密度泛函理论相结合，提供了一个计算溶剂化自由能的框架，该理论专注于溶质 - 溶剂平均力势的间接（溶剂介导）部分ω（间接平均力势）。模拟是在一个假设的充电过程的端点进行的，该过程将溶剂密度从纯液态转变为溶液态。溶剂化自由能的端点DFT表达式可以证明等同于以直接相关函数为关键量的标准表达式，但它的优势在于间接项ω更关注当溶质插入溶液时，相对于纯液体，溶剂 - 溶剂相关性的变化。在这篇展望文章中，我们回顾了端点DFT的最新进展，重点介绍了我们从2017年开始共同撰写的一系列论文。我们强调降维作为评估端点DFT表达式的关键的重要性，并介绍了该理论最近发展的空间分辨版本。利用空间分辨版本可以分析溶液中某些位置的界面水对溶质稳定或不稳定的作用，从端点DFT的角度研究溶剂化变化如何影响蛋白质 - 配体结合和构象景观具有相当大的意义。端点DFT也可应用于材料科学；描述了一个涉及聚合物膜分离合理设计策略的例子。端点DFT方法是一种通过引入近似来对充电参数上的经典密度泛函进行积分以评估溶剂化自由能的方案。我们进一步提出了一种新的泛函，它在充电过程的两个端点都能捕捉间接平均力势ω的正确依赖性，并回顾了它在未来工作中可能的应用方式。
