Interestingly, our results for ff99SB-ILDN and GAFF2 with the HG-optimized radii give a slightly better RMSE than the explicit solvent results from Alibay et al.; 2.8 kcal/mol in explicit solvent and 2.5 kcal/mol in implicit solvent with the HG-optimized radii. However, the results in explicit solvent provide a higher correlation with experimental data than in implicit solvent, R 2 of 0.8 compared to 0.1.