where  is the transmission coefficient (set to 1 in all cases studied herein, based on the fundamental no-recrossing assumption of transition state theory), k B is Boltzmann's In particular, we compared four cases, where the ! dihedral of amide 2 was constrained to 0, ⇡, ⇡/4 and ⇡/2. From the binding/unbinding transition timescales extracted from the 30 infrequent MetaD runs, we could reconstruct the characteristic unbiased kinetics for the events and estimate the characteristic unbinding/binding timescales, ⌧ of f and ⌧ on respectively. For all modeled cases, the kinetic constants for hydroxyde ion release from the amide has been calculated as k of f = 1/⌧ of f . The kinetic constant for hydroxyde ion attack (k on ) can be obtained the same way from ⌧ on -the obtained values have been then corrected considering that our simulation setup is consistent with a hypothetical OH concentration equal to the one of pure water (55.6 M), as the OH ion starts already (and remains) in close proximity of the amide. We could then estimate the equilibrium constant for the amide hydrolysis (K -see Table ) as: