Understanding reactivity in dynamic regimes and in systems in which reactants and products are in continuous exchange is a non-trivial task. Here we report a computational approach that allows us to reconstruct the reactivity in dynamic host-guest systems and to study at atomistic detail the key (molecular and dynamic) factors that control it. As a case study, we focus on the hydrolysis of amide guests encapsulated in the cavity of a coordination cage, for which experimental evidence for reaction acceleration has been recently reported. By combining a multi scale modeling scheme with metadynamics simulations, we couple the study of the intrinsic dynamics of the host-guest system with that of the amide hydrolysis reaction. The approach allow us (i) to characterize the barriers to the hydrolysis reaction as a function of the conformation assumed by the amide, (ii) to study the conformations that the amide guest can assume and estimating their relative probabilities in vs. out the cage cavity, and (iii) to characterize the dynamic processes of guest encapsulation/expulsion in/out the cage. Altogether, we demonstrate how this allows us to reconstruct the reactivity in such dynamic host-guest systems by calculating the relative reactivity of the various molecular conformers/arrangements that the amide guest can assume, to what extent the reactive conformations are more/less favored in vs. out the cage, and by re-weighting the results considering the probability for effective having the guest encapsulated inside the cage cavity. This allows us to estimate a reaction acceleration score, which estimates to what extent the reaction is accelerated/hindered in the host-guest system and allow comparing between system variants.