Suite 2020 3

Post-simulation MM/GBSA analysis was performed by using the thermal_MMGBSA.py script of the Prime/Desmond module of the Schrodinger suite 2020-3 [27 (link),28 (link)]. From each MD trajectory, every 10th frame was extracted from the last 50 ns of simulated trajectories, averaging over 50 frames, for binding free energy calculations of teicoplanin. The Prime MM/GBSA method uses rule of additivity wherein total binding free energy (Kcal/mol) represents a summation of individual energy modules like coulombic, covalent, hydrogen bond, van der Waals, self-contact, lipophilic, solvation, and π-π stackings of ligand and protein.[38] (link)

MM/GBSA technique was exploited as a post-docking validation protocol. The binding energy computed by Prime MM/GBSA of Schrödinger Suite 2020-3 [27 (link),28 (link)] demonstrates an adequate estimation of binding affinity. The MM/GBSA protocol implemented in Prime combines OPLS molecular mechanics energies, a VSGB solvation model for polar solvation (G_SGB), and a nonpolar solvation expression (G_NP) involving nonpolar solvent-accessible surface area (SASA) and van der Waals interactions [29] (link). For each docked teicoplanin-M^Pro complex, Prime MM/GBSA estimated the binding free energy (ΔG_bind) of teicoplanin according to the equation [30] (link). $\Delta G_{bind}=\Delta E_{MM}+\Delta G_{solv}+\Delta G_{SA}$
Where, ΔE_MM is the difference in energy between the complex structure and the sum of the energies of the protein with and without teicoplanin, ΔG_solv is the difference in the GBSA solvation energy of the teicoplanin-protein complex and the sum of the solvation energies for the teicoplanin-bound and unbound protein, and ΔG_SA is the difference in the energy of surface area for the teicoplanin-M^Pro complex and the sum of the surface area energies for the ligand and un-complexed protein.