Assessing the performance of MM/PBSA and MM/GBSA methods. 4. Accuracies of MM/PBSA and MM/GBSA methodologies evaluated by various simulation protocols using PDBbind data set

By using different evaluation strategies, we systemically evaluated the performance of Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) methodologies based on more than 1800 protein-ligand crystal structures in the PDBbind database. The results can be summarized as follows: (1) for the one-protein-family/one-binding-ligand case which represents the unbiased protein-ligand complex sampling, both MM/GBSA and MM/PBSA methodologies achieve approximately equal accuracies at the interior dielectric constant of 4 (with rp = 0.408 ± 0.006 of MM/GBSA and rp = 0.388 ± 0.006 of MM/PBSA based on the minimized structures); while for the total…