Ring Flip of Proline Residue via the Transition State with an Envelope Conformation

Abstract

The ring flip of proline residue in N-acetyl-l-proline-N‘-methylamide (Ac-Pro-NHMe) with trans and cis peptide bonds was studied by adiabatic optimizations along the torsion angle χ1 of the prolyl ring at the HF/6-31+G(d) level. By analyzing the potential energy surface and local minima, it is observed that the prolyl ring flips from a down-puckered conformation to an up-puckered one through the transition state with an envelope form having the N atom at the top of envelope and not a planar one for both trans and cis conformers. At the B3LYP/6-311++G(d,p) level, the barriers to ring flip ΔG‡down→up are estimated to be 2.58 and 3.00 kcal/mol for trans and cis conformers at room temperature, respectively.