On the other hand, participants in past D3R Grand Challenges have reported poor correlations between their estimated MM-GBSA binding scores and experimental affini-ties . In fact, MM-GBSA and MM-PBSA are not always accurate methods for drug design projects because the quality of the results appears to depend on the protein-ligand system, the ligand sets, and details used in the method, such as the interior dielectric constant, the continuum-solvation method, the charges, and the entropies .