QUANTUM-CHEMICAL MODELING OF THE EFFECT OF PROLINE RESIDUES ON PEPTIDE CONFORMATION

Semiempirical AM1 calculations were performed for quantum chemically o ptimized minimum-energy conformations of L-alanine oligomers (A)(n) at n = 7 and their derivatives containing one, two, or three proline res idues at various positions along the peptide chain. The effect of prol ine residues on the peptide conformation was quantified in terms of th e conformational ''strain energy'' and also analyzed in terms of the s patial compatibility of peptides. The defined ''strain energy'' corres ponds to the transformation of the polyalanine peptide from its minimu m conformation to the conformation corresponding to that of the prolin e-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 it s N-terminal part. Also, the regular cr-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 im plications in the prediction of the protein secondary structure, as we ll as in the design of peptide inhibitors and substrates for enzymes a nd receptors. (C) 1998 John Wiley & Sons, Inc.