To our purpose, the reactivity of the different conformers of 2 has to be put into context, namely, considering the actual probability for finding such conformers in solution vs. in the different encapsulated systems (i.e., under different crowding conditions). In realistic conditions, amide bonds are usually found in trans configurations with a torsion angle ! close to ⇡, with a sparse population in cis conformation (! ⇠ 0). The degree of steric conflict of the two residues flanking the amide bond is typically larger in cis amides, resulting, for example, in only ⇠ 5 6% occurrence of cis peptide bonds in protein structures. To estimate the relative probabilities for finding in different conformers in different conditions, we used WT-MetaD simulations.