2) inside the cavity of 1. For evaluation of the kinetics constant of the guests encapsulation/expulsion in/out the cage cavity, we conducted multiple infrequent WT-MetaD simulations in which the encapsulations/expulsion of the amide have been activated. In these WT-MetaD simulations, we used as the CVs the contacts between heavy atoms of guest and host-cage (CV1), the host-to-guest center-to-center distance (CV2), and the standard deviation of the contacts between heavy atoms of the guest and of the host-cage (CV3).