In these equations, ΔEMM, ΔGbind, solv, and −TΔS are calculated in the gas phase. ΔEMM is the gas phase molecular mechanical energy changes which includes covalent, electrostatic, and van der Waals energies. Based on previous studies, the entropy change during binding is small and neglected in these calculations.48−50 ΔGbind, solv is the solvation free energy which comprises the polar and nonpolar components. The polar solvation is calculated using the MMPBSA method by setting a value of 80 and 2 for solvent and solute dielectric constants. The nonpolar free energy is simply estimated from the solvent accessible surface area (SASA) of the solute from the eq 5.