We found that the predicted affinities of ligands modeled in a neutral state (n=18) exhibited better rank correlation (Kendall's τ of 0.44 ± 0.15) with experiment than those for ligands modeled with a +1 charge (Kendall's τ of 0.19 ± 0.07). This suggests that neutral ligands are more amenable to MM-GBSA calculations. Sun et al. have reported ligand binding affinity prediction accuracy degrading with net charge of the ligand. Their Pearson's r degraded from 0.608 ± 0.003 for ligands with net charge zero to 0.564 ± 0.003 for those with net charge one. It is to be noted here, that in our study the sample size for neutral ligands is small (only 18 ligands).