Ab initio analysis of the conformational changes of the prolyl-proline model peptide

For--Pro--Pro-NH₂ is an ab initio model of the prolyl-proline sequence unit present in numerous peptides and proteins. Cis–trans isomerization of the peptide linkage is a crucial step in accessing the active conformation of several proline containing macromolecules.

The present study focuses on the flexibility of the five-membered pyrrolidine ring, which is considered to help other conformational changes as well as cis–trans isomerization. Ring flexibility is characterized by the pseudorotational amplitude, A, and the phase angle, P. Calculations are carried out at the RHF/6-31+G(d) level of theory. The choice of method and level of theory is further supported by single point DFT calculations.

In the course of NMR structure determination of peptides or proteins, proline residues present in the sequences need special attention. Because of the lack of an amide hydrogen, sequential assignment of proline is rather complicated. Furthermore, in solution state, peptide cis–trans isomers are almost always present. Ab initio study on the For--Pro--Pro-NH₂ model is a useful tool to discover the structural characteristics of the prolyl-proline sequence unit.