This simulation approach allowed us to obtain an throughout thermodynamic and dynamic characterization of the reaction as a function of the amide conformation (for some relevant discrete ! values). The results of Figure show a strong dependency of reactivity on the ! dihedral. As expected, the lowest reactivity against hydroxyde attack was observed for the trans conformer, while the cis and the twisted cis amide conformers were found as more reactive. In particular, the latter is the only conformer with a K reac = k on /k of f >1 (Figure : R is higher in free energy than TI -see complete data in Table ). In particular, from the K data, we can obtain relative reactivity scores ( ! ) useful to compare the reactivity between the different amide conformers. The ! scores of Figure (right secondary y axis) clearly show how, compared to the twisted cis amide conformer (!=⇡/4), the cis amide (!=0) is ⇠ 1000 times less reactive, while the reactivity of the trans amide conformer (⇡) is basically negligible (⇠ 10 9 times less reactive than the ⇡/4 conformer).