Degree of pyramidality governs the height and peak position of the free-energy-barrier for the cis-trans isomerization of N-Methylacetamide

► The cis-trans isomerization of N-Methylacetamide was studied by MD simulations with a hybrid QM/MM potential. ► The improper dihedral angle, C(O)NHC(H3) correlates well with the degree of the pyramidal conformations. ► The role of degree of the pyramidal conformation with respect to the isomerization processes was investigated. ► It is found that it governs the height and peak position of the free-energy barriers and the hydration structure.