For the hydration free energy tests, we focused on non-ionized molecules, thus avoiding ambiguity in interpreting the experimental data. The data are drawn from the FreeSolv database, which has been tried and tested in previous studies. The FreeSolv database currently contains 643 neutral small molecules. We selected 100 molecules containing only hydrogen, carbon, nitrogen, and oxygen atoms. With the chosen molecules, the ∆G solv ranges from +3 kcal/mol to -25 kcal/mol. The chemical structures are shown in Figure .