The structures from the docking calculations were used to prepare the systems for molecular dynamics (MD) simulations with System Builder. For non-covalently docked poses, mutated Ala198 was first reverted to Ser198, then TIP4P water molecules were added up to 10 Å from the protein surface to solvate the protein in a orthorombic box. Next, Na + and Cl -ions were added to neutralise the system and produce the final 0.15 M concentration. OPLS_2005 force field was used for parametrisation of the macromolecule as well as the ligand. Default Desmond relaxation protocol (desmond_npt_relax.msj) was used for the equilibration stage: (1) 100 ps of Brownian Dynamics NVT, 10 K, small timesteps, with restraints on the solute heavy atoms, (2) 12 ps NVT, 10 K, with small timesteps and restraints on the solute heavy atoms, (3) 12 ps NPT, 10 K, and restraints on the solute heavy atoms, (4) 24 ps unrestrained NPT; followed by the production stage. The following setup was used for the MD production stage: 1.2 ps interval for energy, isothermal-isobaric NPT ensemble at 300 K and 1.013 bar pressure with Langevin thermostat and barostat (1 and 2 ps relaxation time, respectively, isotropic coupling), RESPA integrator with 2 fs time step, cut-off scheme at 9.0 Å, and random seed. The simulations times were 20-1000 ns with 1000 frames per trajectory. The simulation results were analysed using the built-in Desmond tools. In addition, the binding pose metadynamics for the compound 6 case A and B poses obtained from non-covalent docking followed the default workflow (10 simulations/pose).