Nevertheless, there are advantages to performing an ensemble of long simulations rather than the splitting protocol. Namely, there are key poses and contacts identified during the long timescale protocol which are highly unlikely to be observed by the shorter timescale splitting protocol. In Figure (top), we see three tofacitinib-ADRP contacts which were observed during the long timescale protocol, but not during the splitting protocol. These contacts occur with residues ASN37, LEU53 and VAL36. Upon inspection, we find that all three residues are buried deep within site C (the crystallographically determined binding site). This indicates that a long duration of wall time is typically required in order to explore these "rare" poses as access is required to more buried regions of the ADRP active site. It should be noted that such contact frequency peaks corresponding to conformations that are exclusively sampled in the "long" trajectories are present much more prominently in case of all other systems studied (see Figure ).