Force Field Benchmark of Organic Liquids. 2. Gibbs Energy of Solvation

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. <i>J. Comput. Chem.</i> <b>2004</b>, <i>25</i>, 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 (