Laboratorium für Physikalische Chemie, ETH Zürich, ETH-Hönggerberg, HCI, CH-8093 Zürich, Switzerland.
Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil.
J Chem Theory Comput. 2020 Dec 8;16(12):7556-7580. doi: 10.1021/acs.jctc.0c00688. Epub 2020 Nov 4.
Experimental solvation free energies are nowadays commonly included as target properties in the validation and sometimes even in the calibration of condensed-phase force fields. However, this is often done in a nonsystematic fashion, by considering available solvation free energies involving an arbitrary collection of solutes in a limited set of solvents (e.g., water, octanol, chloroform, cyclohexane, or hexane). Here, this approach is made more systematic by introducing the concept of cross-solvation free energies Δ for a set of molecules that are all in the liquid state under ambient conditions, namely the matrix of entries for Δ considering each of the molecules either as a solute (A) or as a solvent (B). Relying on available experimental literature followed by careful data curation, a complete Δ matrix of 625 entries is constructed for 25 molecules with one to seven carbon atoms representative for alkanes, chloroalkanes, ethers, ketones, esters, alcohols, amines, and amides. This matrix is then used to compare the relative accuracies of four popular condensed-phase force fields: GROMOS-2016H66, OPLS-AA, AMBER-GAFF, and CHARMM-CGenFF. In broad terms, and in spite of very different force-field functional-form choices and parametrization strategies, the four force fields are found to perform similarly well. Relative to the experimental values, the root-mean-square errors range between 2.9 and 4.0 kJ·mol (lowest value of 2.9 for GROMOS and OPLS), and the average errors range between -0.8 and +1.0 kJ·mol (lowest magnitude of 0.2 for AMBER and CHARMM). These differences are statistically significant but not very pronounced, especially considering the influence of outliers, some of which possibly caused by inaccurate experimental data.
目前，实验溶剂化自由能通常被纳入验证中，有时甚至纳入凝聚相力场的校准中，作为目标性质。然而，这通常是通过考虑任意集合的溶质在有限溶剂集合（如水、辛醇、氯仿、环己烷或己烷）中的可用溶剂化自由能来完成的，这种方法缺乏系统性。在此，通过引入交叉溶剂化自由能Δ的概念，使方法变得更加系统，该概念适用于一组在环境条件下均处于液态的分子，即对于Δ的矩阵，其中考虑到每种分子可以是溶质（A）或溶剂（B），共有 625 个条目。基于现有的实验文献，并进行仔细的数据整理，为具有 1 到 7 个碳原子的 25 个分子构建了一个完整的 Δ矩阵，这些分子代表了烷烃、氯代烷烃、醚、酮、酯、醇、胺和酰胺。然后，使用该矩阵比较了四种流行的凝聚相力场的相对准确性：GROMOS-2016H66、OPLS-AA、AMBER-GAFF 和 CHARMM-CGenFF。总的来说，尽管力场的功能形式选择和参数化策略有很大差异，但这四种力场的性能都非常相似。相对于实验值，均方根误差范围在 2.9 和 4.0 kJ·mol（GROMOS 和 OPLS 的最低值为 2.9）之间，平均误差范围在-0.8 和+1.0 kJ·mol（AMBER 和 CHARMM 的最低值为 0.2）之间。这些差异具有统计学意义，但并不十分明显，尤其是考虑到离群值的影响，其中一些可能是由实验数据不准确引起的。
