We first minimized the ligand, water, and the ions for 1000 steps with 25 kcal/mol-Å2 positional restraints on the protein, followed by another 1000 steps of minimization with the protein restraints reduced to 10 kcal/mol-Å2 . Next, the system was heated from 10 K to 300 K in NVT ensemble for 140 ps with 10 kcal/mol-Å2 restraints on the protein-ligand complex. We then successively decreased the restraints on the protein-ligand complex for 20 ps to first 5 and then to 2 kcal/mol-Å2 , followed by 2 kcal/mol-Å2 restraint only on the ligand. We used Langevin thermostat with a collision frequency of 2 ps -1 to maintain the temperature of the system. We simulated the system for 14 ns in NPT ensemble for the production run. Isotropic pressure scaling was used to regulate the pressure with a relaxation time of 2 ps. The first four ns was discarded as equilibration.