Previous studies on cucurbiturils have provided some highlights and important factors to consider . First, we note that since CB8 is fairly rigid, sampling of the host may be straightforward. However, cucurbiturils and other SAMPL hosts have been observed to collapse in on themselves with certain force fields , which is thought to limit guest sampling, affect convergence, and result in overestimated free energies. Second, guest binding modes have been shown to be more challenging to adequately sample , especially when the guest is more flexible. Perhaps more relevant to this dataset is that cucurbiturils are known to modulate protonation states of guests upon binding .