In addition, by executing both the long-timescale and splitting protocols we have provided insight into the utility of adaptive sampling protocols. With respect to the length of simulations, it is clear that the merit of running a long simulation changes as a function of the timescale of events of interest. In the case of the systems studied here, no long timescale events (e.g. large-scale domain rearrangements) need to occur for ligand binding to be possible. As a result, a simple adaptive sampling protocol was able to successfully identify all of the sites identified by the long timescale protocol albeit with significantly less wall time required (1 day 7 hours for adaptive sampling as compared to 43 days 2 hours for 10 microseconds of simulation for the ADRP system).