Puckering transitions of pseudoproline residues.

The puckering transitions of pesudoprolines such as oxazolidine and thiazolidine residues (Oxa and Thz dipeptides) with trans and cis prolyl peptide bonds were explored by optimizations along the endocyclic torsion angle chi(1) using quantum-chemical methods in the gas phase and in water. The overall shapes of the potential energy surfaces for Oxa and Thz dipeptides in the gas phase and in water are similar to those for the Pro dipeptide, although there are some differences in relative stabilities of local minima and in barriers to puckering transition. On the whole, the barriers to puckering transition for Oxa and Thz dipeptides are computed to be 0.8-3.2 kcal/mol at the B3LYP/6-311++G(d,p) level in the gas phase and in water, which are lower by 0.5-1.9 kcal/mol than those for the Pro dipeptide. The n --> sigma* interactions for the delocalization of the lone pair of the prolyl amide nitrogen into the antibonding orbitals that are anti to the lone pair appear to play a role in stabilizing the nonplanar puckered transition states over the corresponding planar structures. The calculated barriers indicate that the down-to-up puckering transition can proceed in the orders Pro < Oxa < Thz in the gas phase and Pro approximately Oxa < Thz in water. (c) 2009 Wiley Periodicals, Inc. Biopolymers 91: 444-455, 2009.