Binding free energy calculation using MM-PBSA

The free energy calculation provides a quantitative estimation of interactions between protein and ligand that help to understand the stability of that protein–ligand complex [18]. The binding free energy including the free solvation energy (polar and nonpolar solvation energies) and potential energy (electrostatic and Vander Waals interactions) of each protein–ligand complexes was calculated by the Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) method. The MD trajectories were processed before doing MM-PBSA calculations for last 1 ns. The MM-PBSA binding free energy calculation was done with ‘g_mmpbsa’ [18] script. The binding energy is calculated by using the following equation:

where ΔG binding = the total binding energy of the complex, G receptor = the binding energy of free receptor, G ligand = the binding energy of unbounded ligand.