For systems with compounds 1 and 2r (Figure ), 10,000 frames were sampled out of all trajectory data, using the MSM stationary probabilities as weights. These trajectories were used to compute the residue behaviour shown in Figure . To obtain the reference active and inactive conformation ensembles, the same was applied to the reference system. However, instead of the stationary probabilities, metastable distributions for the active and inactive states were used.