MM-PBSA calculations

Binding free energies (ΔG_Bind) of the protein–ligand complexes were calculated from molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) evaluated by adaptive Poisson–Boltzmann solver 3.0 (APBS 3.0) using g_mmpbsa package [44, 45]. The MM-PBSA approach is one of the most widely used methods to compute interaction energies among the biomolecular complexes. Together with MD simulation, MM-PBSA can decode significant conformational fluctuations and entropic contributions to the binding energy. In general, the binding free energy (G_Bind) between a protein and a ligand in solvent can be expressed as:

where G_Complex is the total free energy of the protein − ligand complex and G_Protein and G_Ligand are total free energies of the separated protein and ligand in solvent, respectively. The same equation can be used to calculate other types of biomolecular interactions such as protein − protein, protein − DNA complexes, etc.