RESUMO
Collagen is the most abundant human protein, with the canonical sequence (Gly-Pro-Hyp)n in its triple helix region. Cis-trans isomerization of the Xaa-Pro amide has made two of these amide bonds the target of alkene replacement: the Gly-Pro and the Pro-Hyp positions. The conformations of Gly-Pro and Pro-Pro (as a Pro-Hyp model) fluoro-, chloro-, and proteo-alkene mimic models were investigated computationally to determine whether these alkenes can stabilize the polyproline type II (PPII) conformation of collagen. Second-order Møller-Plesset (MP2) calculations with various basis sets were used to perform the conformational analyses and locate stationary points. The calculation results predict that fluoro- and chloro-alkene mimics of Gly-Pro and Pro-Pro can participate in nâπ* donation to stabilize PPII conformations, yet they are poor nâπ* acceptors, shifting the global minima away from PPII conformations. For the proteo-alkene mimics, the lack of significant nâπ* interactions and unstable PPII-like geometries explains their known destabilization of the triple helix in collagen-like peptides.