For reference, we also performed standard MD and MD/MC simulations using the same total number of energy evaluations. In the MD case, this meant 5000 iterations of 20000 MD steps. And in the MD/MC case, this meant 5000 iterations of 20000 MD steps interspersed by 10 conventional MC move proposals involving random ligand rotation. The number of energy evaluations at each iteration was kept constant between methods. Thus, with a 2fs timestep we simulated for an equivalent of 200ns total with each method.