is in. We should clearly see two distinct and equally populated binding modes in molecular simulations. This is a trivial test but it is a good proof-of-principle because we know what the right answer is and we can test whether we recover this quickly/accurately. As a point of comparison, we ran a standard 100 ns MD simulation and also monitored the orientation of this ring. Figure shows the binding modes sampled during the MD and MD/NCMC simulations and the probability of the two binding modes as a function of time. We saw only a single transition between the two binding modes during the entire course of the MD simulation, while with MD/NCMC there were frequent transitions between the two binding modes. Since there were not enough transitions in the MD simulations, the populations of the two binding modes did not converge to the 'ideal' 50/50 probability. On the other hand, the populations of the two binding modes converged to the expected values in the MD/NCMC simulations. Thus, MD/NCMC was not only able to increase the transition rate, but it also sampled correctly from the Boltz-mann distribution.