Intramolecular interactions and cis peptidic bonds

The cis Gly–Gly peptidic bond observed in dihydrofolate reductase, which takes place between a beta sheet and an alpha helix is chosen as an example to study the various factors which influence this conformation. The peptidic chain of 16 amino acids is studied by a QM/MM scheme (6-31+G* B3LYP—Amber 99). Both electronic and classical contributions to the total energy take part to the stabilization of the cis conformation. A special role is played by the alpha helix when it is bonded to the carbonyl group of the bond of interest.