The MD simulations were carried out using the pmemd.cuda module of the Amber18 simulation package . We used Antechamber (from Amber 16 package ) to add partial charges to the ligand atoms using the AM1-BCC model . Tleap, an auxiliary program of Amber16 was used to set up the simulation box and parameters. The protein and the ligands were modeled using the Amberff99sb and GAFF version 1.8 force fields respectively. The protein-ligand complex was then solvated in TIP3P water in a cubic box with 10 Å padding. Na+ and Cl-counter ions were added to achieve a salt concentration of 0.1M with additional Cl-ions to ensure that the system was neutral. SHAKE was used to constrain the protein heavy atomhydrogen bonds with a time step of 2 fs. Long-range electrostatic interactions were calculated using the particle mesh Ewald method, with a cutoff of 9.0 Å for the real space electrostatics and Lennard-Jones forces.