Transition of prolyl puckering in a model of polyproline

The transition of the proly]. ring for N-acetyl-L-proline-N',N'-dimethylamide (Ac-Pro-NMe2) with trans and cis peptide bonds as models for polyproline II (PPII) and polyproline I (PPI), respectively, was studied by adiabatic optimizations along the torsion angle X 1 of the prolyl ring at the ab initio 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 PPII and PPI conformers. At the density functional B3LYP/6-311++G(d,p) level, the barriers to ring flip Delta G(down -> up)(double dagger) are estimated to be 2.22 and 2.73 kcal/mol for PPII and PPI conformers at room temperature, respectively, which are lower by down-up similar to 0.3 kcal/mol than those of N-acetyl-L-proline-N'-methylamide (Ac-Pro-NHMe). These results may imply that the prolyl ring of polyproline could be more likely to flip than that of non-polyproline sequence. (c) 2004 Elsevier B.V. All rights reserved.