MM/PBSA free energy calculation

The MM/PBSA (Molecular Mechanics Poisson Boltzmann Surface Area) technique was utilized for the calculation of the binding energy of the protein–ligand complexes. MMPBSA is a collective energy of the system, which is represented by the van der Waal energy, electrostatic energy, SASA energy, and binding energy of the system. In MM-PBSA, the polar part of the solvation energy is calculated by using the linear relation to the solvent accessible surface area. In the present study, the g_mm-pbsa module of GROMACS was applied for the determination of different components of the binding free energy of complexes [25]. Considering the convergence issue associated with MM-PBSA calculations, only the last 10 ns of data were utilized for the analysis. It is to be noted that the entropy calculations were not done in the current study that could change the numerical values of the binding free energy reported for the compounds.