†Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
‡Uppsala Center for Computational Chemistry, Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Husargatan 3, Box 596, SE-75124 Uppsala, Sweden.
J Chem Inf Model. 2015 Jun 22;55(6):1192-201. doi: 10.1021/acs.jcim.5b00106. Epub 2015 Jun 3.
Quantitative prediction of physical properties of liquids is a longstanding goal of molecular simulation. Here, we evaluate the predictive power of the Generalized Amber Force Field (Wang et al. J. Comput. Chem. 2004, 25, 1157-1174) for the Gibbs energy of solvation of organic molecules in organic solvents using the thermodynamics integration (TI) method. The results are compared to experimental data, to a model based on quantitative structure property relations (QSPR), and to the conductor-like screening models for realistic solvation (COSMO-RS) model. Although the TI calculations yield slightly better correlation to experimental results than the other models, in all fairness we should conclude that the difference between the models is minor since both QSPR and COSMO-RS yield a slightly lower RMSD from that of the experiment (<3.5 kJ/mol). By analyzing which molecules (either as solvents or solutes) are outliers in the TI calculations, we can pinpoint where additional parametrization efforts are needed. For the force field based TI calculations, deviations from the experiment occur in particular when compounds containing nitro or ester groups are solvated into other liquids, suggesting that the interaction between these groups and solvents may be too strong. In the COSMO-RS calculations, outliers mainly occur when compounds containing (in particular aromatic) rings are solvated despite using a ring correction term in the calculations.
定量预测液体的物理性质是分子模拟的一个长期目标。在这里，我们使用热力学积分（TI）方法评估通用 Amber 力场（Wang 等人，J. Comput. Chem. 2004, 25, 1157-1174）对有机溶剂中有机分子溶剂化吉布斯自由能的预测能力。结果与实验数据、基于定量结构性质关系（QSPR）的模型以及现实溶剂化的导体相似性屏蔽模型（COSMO-RS）模型进行了比较。尽管 TI 计算与实验结果的相关性略好于其他模型，但公平地说，我们应该得出结论，这些模型之间的差异很小，因为 QSPR 和 COSMO-RS 与实验相比的 RMSD 略低（<3.5 kJ/mol）。通过分析 TI 计算中的哪些分子（无论是溶剂还是溶质）是离群值，我们可以指出需要进行额外参数化的地方。对于基于力场的 TI 计算，当含有硝基或酯基的化合物被溶解到其他液体中时，与实验的偏差特别大，这表明这些基团与溶剂之间的相互作用可能太强。在 COSMO-RS 计算中，当包含（特别是芳环）环的化合物被溶解时，尽管在计算中使用了环校正项，但离群值主要出现。
