Center for Molecular Biosciences Innsbruck, Department of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 80/82, Innsbruck, Austria.
J Chem Phys. 2022 May 28;156(20):204101. doi: 10.1063/5.0087549.
Grid Inhomogeneous Solvation Theory (GIST) has proven useful to calculate localized thermodynamic properties of water around a solute. Numerous studies have leveraged this information to enhance structure-based binding predictions. We have recently extended GIST toward chloroform as a solvent to allow the prediction of passive membrane permeability. Here, we further generalize the GIST algorithm toward all solvents that can be modeled as rigid molecules. This restriction is inherent to the method and is already present in the inhomogeneous solvation theory. Here, we show that our approach can be applied to various solvent molecules by comparing the results of GIST simulations with thermodynamic integration (TI) calculations and experimental results. Additionally, we analyze and compare a matrix consisting of 100 entries of ten different solvent molecules solvated within each other. We find that the GIST results are highly correlated with TI calculations as well as experiments. For some solvents, we find Pearson correlations of up to 0.99 to the true entropy, while others are affected by the first-order approximation more strongly. The enthalpy-entropy splitting provided by GIST allows us to extend a recently published approach, which estimates higher order entropies by a linear scaling of the first-order entropy, to solvents other than water. Furthermore, we investigate the convergence of GIST in different solvents. We conclude that our extension to GIST reliably calculates localized thermodynamic properties for different solvents and thereby significantly extends the applicability of this widely used method.
格子不均匀溶剂化理论（GIST）已被证明可用于计算溶质周围水的局部热力学性质。许多研究都利用了这一信息来增强基于结构的结合预测。我们最近将 GIST 扩展到氯仿作为溶剂，以允许预测被动膜的通透性。在这里，我们进一步将 GIST 算法推广到所有可以建模为刚性分子的溶剂。这种限制是方法固有的，已经存在于不均匀溶剂化理论中。在这里，我们通过将 GIST 模拟的结果与热力学积分（TI）计算和实验结果进行比较，表明我们的方法可以应用于各种溶剂分子。此外，我们分析并比较了一个由 100 个条目组成的矩阵，其中包含 10 种不同溶剂分子在彼此内部的溶剂化。我们发现，GIST 的结果与 TI 计算和实验高度相关。对于一些溶剂，我们发现与真实熵的皮尔逊相关系数高达 0.99，而其他溶剂则受到一阶近似的影响更大。GIST 提供的焓熵分裂使我们能够扩展最近发表的一种方法，该方法通过一阶熵的线性标度来估计高阶熵，从而将其应用于水以外的溶剂。此外，我们还研究了 GIST 在不同溶剂中的收敛性。我们得出结论，我们对 GIST 的扩展能够可靠地计算不同溶剂的局部热力学性质，从而显著扩展了这种广泛使用的方法的适用性。
