Conventional MD simulations were performed using the CUDA version of the PMEMD module of the AMBER 16 simulation package. The protein, ligands and solvent were described using the ff14SB force field, the General AMBER Force Field 2 (GAFF2), and the TIP3P water model, 66 respectively. Following initial minimization and equilibration, each system (summarized in Table ) was subjected to 10 x 500 ns of molecular dynamics simulations controlled by the Langevin thermostat with a collision frequency of 2 ps -1 , 67 and the Berendsen barostat with a 1 ps coupling constant. This led to a cumulative 5 μs of production simulations per system, and a cumulative total of 70 μs of conventional MD simulations over all systems studied (Table ).