A well-converged WT-MetaD simulation, allowed us to reconstruct the FES associated with the system. This provided us with a reliable estimation of the free-energy differences (∆G) between all the "bound" and "unbound" states the system visits multiple times during the simulation. However, due to its high deposition rate, the energy bias can be deposited over the transition states and can affect the kinetic barrier. Additionally, the ∆G profile obtained from the simulation (Fig. , top panel: ∆G, black curve) shows low barriers between intermediate states, suggesting that the set of variables is well suited to describe the translational motion of the macrocycle, but may not be optimal for describing the transition from the bound state. Therefore, we used a different strategy to estimate the transition barriers (∆G ‡ ) and kinetic information on the shuttling dynamics (τ : characteristic transition timescales between the various states). As recently done for studying rare transitions in other supramolecular systems, we ran multiple infrequent WT-MetaD simulations where the transition between metastable states is accelerated/biased and can thus be effi-ciently sampled. Provided that the simulations' setup is appropriate, and the CVs are able to distinguish among different basins, it is then possible to reconstruct the unbiased/native transition kinetics from the infrequent WT-MetaD biased one. In particular, we ran multiple infrequent WT-MetaD simulations activating the transition from main "bound" minimum A (Fig. ) to the "unbound" state (D).