While we find MM-GBSA performs poorly here, a variety of previous literature results have reported reasonable performance and positive correlations between calculated binding scores and experimental affinities . The GB-Neck2 model used in this work is a relatively new GBSA model and has not been widely tested for protein-ligand binding affinity rankings. However, Su et al. used it successfully in their QM-MM/GBSA work on benzimidazole inhibitors . It is also possible that successes of MM-GBSA may be published more often than failures so our sampling of the literature could be subject to publication bias. Moreover, participants in previous D3R challenges found a poor correlation between MM-GBSA free energy estimates and experimental binding affinities . In the best case scenario, MM-GBSA is expected to be consistent with the results generated using the MM-PBSA method (molecular mechanics -Poisson-Boltzmann surface area), which itself has been shown to be an unreliable method .