3.8. Free Energy Calculation Using MM/GBSA Approach

To estimate the binding affinity (ΔG_bind), we used the Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) method [80,120,121]. The ΔG_bind was calculated according to the following equations:

The affinity energy (ΔGbind) is the summation of the interaction energy of the gas phase between protein-ligand (ΔEMM), desolvation free energy (ΔGsolv) and system entropy (-TΔS). ΔEMM is the result of the sum of internal energy (ΔEinternal, sum of the energies of connection, angles, and dihedral) electrostatic contributions (ΔEele) and the van der Waals term (ΔEvdW). ΔGsolv is the sum of the polar (ΔGGB) and non-polar (ΔGNP) contributions. ΔGSA was determined from the solvent accessible surface area (SASA) estimated by the linear combination of pairwise overlaps (LCPO) algorithm.