Quantum chemical modelling of the effect of proline residues on peptide conformation

Semiempirical AM1 calculations were performed for quantum chemically optimized minimum-energy conformations of L -alanine oligomers (A)_n at n = 7 and their derivatives containing one, two, or three proline residues at various positions along the peptide chain. The effect of proline residues on the peptide conformation was quantified in terms of the conformational “strain energy” and also analyzed in terms of the spatial compatibility of peptides. The defined “strain energy” corresponds to the transformation of the polyalanine peptide from its minimum conformation to the conformation corresponding to that of the proline-containing peptide. The results of calculations indicate that the “strain effect” of proline residues is additive at all locations along the peptide chain, except at the first and the second positions of its N-terminal part. Also, the regular α-helical polyalanine structure was most significantly altered by the presence of some specific motifs around the proline location in the peptide. This, in turn, has its implications in the prediction of the protein secondary structure, as well as in the design of peptide inhibitors and substrates for enzymes and receptors. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 66 : 391–396, 1998