Protein-ligand complexes were assembled with the tleap tool using AMBER16SB, as the force field for the protein. The systems were explicitly solvated by a cubic water box with cell borders placed at least 13 Å away from any protein or ligand atom using TIP3P as the water model. To neutralize the total charge, Na + /Cl - counterions were added to a final salt concentration of 0.15M. The systems were energy minimized for 1000 steps with the conjugate-gradient method and then 50,000 steps of NVE (100 ps) ensemble (micro-canonical ensemble; constant number of particles (N), constant volume (V), constant energy (E)) followed by 1 ns of NPT (Isothermal-isobaric ensemble; constant number of particles (N), constant pressure (P), constant temperature (T)) simulation, both using a time step of 2 fs and applying harmonic position constraints on protein and ligand atoms, which were gradually reduced with a scaling factor of 0.1. Pressure was maintained at 1 atm using a Berendsen barostat. The Langevin thermostat was set with a low damping constant of 1 ps-1). Bond lengths involving hydrogen atoms were constrained using the M-SHAKE algorithm. The MD production runs were conducted in a NVT ensemble. Long-range Coulomb interactions were treated using the particle mesh Ewald summation method (PME) setting the mesh spacing to 1.0 Å. A nonbonded cutoff distance of 9 Å with a switching distance of 7.5 Å was used.