Simulations of the trypsin-benzamidine system were performed in an almost identical fashion to our previous study, in which we parametrized the protein using the AMBER ff14SB forcefield, 39 *14 with all simulations performed at 298.15 K and, in the MD simulations, with rigid hydrogenheavy atom bonds, and a nonbonded cutoff of 9 Å, and a timestep of 2 fs, using OpenMM. The OpenMM implementation allowed us to check for a collision every time step, instead of every 10 time steps of the previous implementation, which likely improved calculation accuracy. We added some additional milestones to the trypsin-benzamidine system, such that milestones were located at 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, and 18 Å from the center of mass of the binding site.