As previously done for studying, e.g., the dynamics of other types of supramolecular systems at submolecular resolution, here we relied on WT-MetaD and infrequent WT-MetaD simulations to activate and effectively sample the binding/unbinding and shuttling events in the MIMs at atomistic resolution. The characterization of the free-energy landscape in each system is obtained from well-converged WT-MetaD simulations. In WT-MetaD, a history-dependent bias potential acts on selected reaction variables (the collective variables, CV) to drive the system in its exploration of the possible conformations, accelerating the dynamics of recrossing between the various metastable states while, at the same time, allowing to calculate the free-energy of the unbiased system as a function of the biased CVs or of other degrees of freedom via a well-established reweighting procedure. Employing reweighting, we could also estimate the enthalpic contribution as a function of selected CVs, allowing the decomposition of the free-energy into enthalpic and entropic contribution. The convergence of the WT-MetaD simulations was assessed by ensuring the stability of the free-energy minima, associated with the most relevant states of each system, requiring simulation times up to 2 µs. Exploiting the symmetry of the systems, with respect to the axis perpendicular to the axle, the conformational sampling can be effectively symmetrized, improving the convergence and obtaining axially symmetric free-energy plots (see Figs. ). In the SI, we report the choice of the WT-MetaD parameters and CVs for each reported WT-MetaD simulation. To characterize the kinetics of the most significant transitions in the investigated system (unbinding/escape from minimum energy configurations), we relied on the infrequent WT-MetaD protocol, which introduces a properly designed WT-MetaD bias potential to accelerate a selected transition while allowing the reconstruction of its unbiased kinetics. Differently from a converged recrossing WT-MetaD simulation, such an approach based on "directional/irreversible" transitions sampled via multiple replica infrequent WT-MetaD simulations guarantees a more robust estimation of the free-energy barriers and of the associated transition kinetics. This is achieved by performing several infrequent WT-MetaD simulations sampling a selected transition and analyzing the cumulative distribution of unbiased transition times (see SI). A good fit between the obtained transition time distributions and a typical Poissonian distribution expected for a rare event is desirable to guarantee the appropriateness of the adopted simulation setup (see SI -Figs. S3, S6, S8, S10). From the Poissonian fits it is then possible to estimate the characteristic transition timescale (τ ) associated with different transitions as: