Although this NCMC implementation is more efficient on a force evaluation basis compared to MD, there is some computational overhead for alchemically modifying the sterics and electrostatics during integration in OpenMM for GPU simulations, causing the wall-clock time per NCMC iteration to be about three times longer than a MD iteration. Specifically, our calculations shown in Figure took 2249 minutes for MD, 2189 minutes for MD/MC, and 5413 minutes MD/NCMC. Convergence to within uncertainty of the correct population, and to within 5% of the correct population, appears to occur for this system (Figure ) well before 40% of the total simulation time (80ns); with a factor of three in additional cost, this takes about as long to run as 240ns of conventional MD simulation. Thus the savings of NCMC in terms overall wall-clock time is still about a factor of five compared to the MSM approach for this system, which required roughly 1.3µs of aggregate simulation data.