found a free energy of binding of 12.2 ± 3.7 kcal/mol, 67 i.e. a positive free energy of binding energy with the MM/GBSA approach. The difference between our results and those of Hayashino et al. stems mainly from changes in the solvation free energies (∆G pol + ∆G np ) in MM/GBSA and is most likely due to differences in how MM/GBSA is parameterizated.