where ΔEMM was the difference in energy between the ligand-protein complex and the sum of the energies of the ligand and free protein, using the OPLS-2005 force field; ΔGsolv was the difference in the GB/SA solvation energy between the ligand-protein complex and the sum of the solvation energies for the ligand and free protein; and ΔGSA was the difference in the surface area energy between the ligand-protein complex and the sum of the surface area energies for the ligand and free protein. Corrections for entropic changes were not applied. The dielectric constants were set according to solvent water (VSGB2.1 solvation model).