Here, MM-GBSA scores are reported in units of kcal/mol and are based on end-point free energy estimates. However, they should not be confused with true binding free energy calculations , as they involve several additional approximations. Partly as a result, calculated MM-GBSA values are typically much lower (more negative) than experimental binding free energies. The differences arise from the different approximations used to account for the solvation and configurational entropy of the protein and the ligand. Also, water molecules or cavities in the binding pocket are modeled using bulk (continuum) water, which cannot capture the finer details of water-mediated interactions present in explicit water simulations, and in some cases can produce artifactual water placements. Hence in this work, we will be referring the MM-GBSA values as MM-GBSA scores and not MM-GBSA free energies.