Influence Of Proline Endo/exo Conformers On PPII-helices

Protein folding and the structure could decide its functional role directly. The main factor affecting protein folding is intramolecular interactions, also surrounding environments are important too. Polyproline type II(PPII) is a special type of protein’s secondary structure, which is found prevalent in unfolded polypeptides and participates in functional performance including signal transduction, self-assembly, and immune response. However, it’s still puzzled how the helical structure is stabilized. Recent decades, as the development of crystallography, researchers could obtain more crystal structures with high resolution, which make it possible to carry out a series of experimental and theoretical researches.Proline is the most preferred amide of PPII-helices. Because of the lack of amide hydrogen for proline, regular hydrogen bonds rarely exist in the backbone of a polyproline PPII-helix. Recent years, researchers found a kind of long-range noncovalent interaction caused by electron delocalization named n-π* interaction which is much weaker than hydrogen bonds but is abundant in folding proteins. Thus we think whether n-π* interaction is important for the stability of PPII-helices.Via DFT calculations, we found the endo/exo conformers of pyrrolidine rings could influence the strength of n-π* interactions while which is related to the folding degrees of PPII-helices. As a result, exo-type prolines are favored by tight PPIIhelices and could form stronger n-π* interactions on the backbone. However, exo-type prolines are less preferred by long oligomers on energy. By the non-covalent index analysis and an insight of the dipole-moment of PPII-helices, endo-type prolines are found to form stronger interactions by side rings, and we suggest this is a kind of weak dipole-dipole interactions. Thus, prolines make the conformations of PPIIhelices flexible. Beside these quantum calculations, PDB analysis was employed. However because of the lack of crystal structure samples with high resolution, the result of PDB analysis is less accurate than DFT calculations.This work is the first time that point out how endo/exo conformers of prolines influence the flexibility of PPII-helices. It will be helpful for understanding PPIIhelices and might make a help on some protein engineering works.