Next, we minimized each system for 100 ps using a 1 fs timestep, a Brownian motion thermostat at 10 K with a maximum displacement of 0.1 Å per step, while restraining all heavy atoms of the complex with a force constant of 50 kcal/mol/Å 2 . We then thermalized each system using the NVT ensemble with a Langevin thermostat at 10K for 12 ps and keeping the positional restraints as detailed before. While retaining the restraints on the solute's heavy atoms, we perform 20 ps of NVT simulation making GCMC 44 moves every 50 fs followed by an unrestrained 1 ns of simulation with the same GCMC interval. This was to ensure the protein-ligand complex was adequately solvated. We further thermalized each system by running a 10 ns NPT ensemble simulation using Martyna-Tuckerman-Klein (MTK) thermostat/barostat with a 2 fs timestep at 300 K. During this final thermalization stage, we verified the ligand pose's stability by monitoring that its root-mean-squared-deviation (RMSD) did not exceed 2.5 Å with respect to the input conformation.