Our thermodynamic test system, gas-phase water at 500K, allows us to check that we maintain the correct Boltzmann distribution for a system that has a large number of accepted MC tries; here ~57% of the MC steps resulted in a new water configuration. The potential energy distribution provided by the MC/MD method agrees closely with that provided by a pure MD simulation of the same system (Figure ). In addition, the results are highly consistent across all eight MC/MD runs, as shown in Figure , which shows all simulations starting from the same configuration energy, diverging as sampling proceeds, and converging to very similar mean energies. For pure MD, the mean potential energy over 10 7 energy evaluations was -126.8 kcal mol -1 , while the mean potential energy for MC/MD for 10 7 energy evaluations divided into 8 separate 1.25 × 10 6 runs was -127.0 kcal mol -1 (Figure ). The good agreement between pure MD and MC/MD supports the validity of the parallel MC method and its correct maintenance of detailed balance. Hence, it can be used to compute experimental observables, such as binding free energies.