2.5. MM–GBSA

To predict the theoretical free energies of binding of ligands to receptor, generally two most commonly used methods are (a) the molecular mechanics generalized Born surface area (MM-GBSA) and (b) molecular mechanics Poisson–Boltzmann surface area (MM-PBSA). Both methods are equally efficient to predict the correct binding affinities (Chen, 2016; Chen et al., 2015; Hou et al., 2011; Venugopal et al., 2020). Here, we used the MM-GBSA method to calculate the relative binding free energies of green tea polyphenols to Mpro protein. The free energy of binding can be calculated as ΔG_bind = ΔH − TΔS.

ΔH = ΔE_elec + ΔE_vdW + ΔG_polar + ΔG_non-polar, where E_elec and E_vdW are the electrostatic and van der Waal’s contributions, and G_ploar and G_non-polar are the polar and non-polar solvation terms, respectively. The non-polar energy is calculated from the SASA while the polar contribution of the free energy can be estimated using generalized Born model with an external dielectric constant of 80 and internal dielectric constant of 1. The entropic contribution is neglected here due to similar type of ligands bind to the receptor. Therefore, our calculated values are referred to as relative binding free energies. The theoretical binding free energy of the potent inhibitors of Mpro was identified using the prime module of Schrodinger suit (Schrödinger Release 2020-1: Prime, Schrödinger, LLC, New York, NY, 2020). MM-GBSA is a popular method to calculate binding energy, which uses energy properties of free ligand, free receptor and receptor–ligand complex for binding affinity calculation. Binding energies were estimated for the three polyphenols selected based on the binding affinity of AutoDock Vina docking and three complex structures were selected. Then with these docking structures MM-GBSA were calculated.