Ligand 1 has a rotatable bond which can rotate even in the bound configuration, giving rise to two different binding modes separated by a 180 • rotation of the rotatable bond. We refer these two binding modes as 'orig' and 'flip' ( short for 'original' and 'flipped', shown in Figure ). The two phenyl ring orientations are chemically indistinguishable, but distinguishable in simulations because we can number the individual atoms and track which orientation it The number of transitions between the two binding modes per million force evaluations (transitions/million f-ev) is also reported. Probability of the two binding modes, namely 'orig' and 'flip' as a function of time (right). MD/NCMC increases the rate of transition between the two binding modes compared to classical MD simulations, resulting in faster convergence of the population of two binding modes to the 'ideal' distribution.