Dipole interaction model predicted pi-pi* circular dichroism of cyclo(L-Pro)3 using structures created by semi-empirical, ab initio, and molecular mechanics methods.

Abstract

Cyclo(l-Pro)3 (CP3) is a synthetic peptide created to model cis and torsionally strained peptide bonds that also exhibits a strong distinctive UV circular dichroic (CD) spectrum. Circular dichroic spectra were computed for the amide pi-pi* transition using the dipole interaction model for various conformations of the peptide. Conformations of CP3 were created initially from crystal data, and followed by energy minimizations via molecular mechanics using the cvff force field; the effects of additional geometric optimizations by semi-empirical and ab initio quantum mechanics were investigated. The CD spectra for each conformation were calculated using a variety of different parameters, and each result was compared with the published experimental spectrum [Deber, C.M., Scatturin, A., Vaidya, V.M. & Blout, E.R. (1970) Small cyclic proline peptides: UV absorption and CD. In: Peptides: Chemistry and Biochemistry, Proceedings of the First American Peptide Symposium (Weinstein, B., ed.), Marcel Dekker, New York pp. 163-173]. Herein, two distinct conformations, a C3 symmetric and an asymmetric form, gave CD predictions that separately did not resemble the experimental spectrum. Energy differences were predicted at various theoretical levels, including MP2 and density functional theory. When the predicted CD spectra for each conformation were multiplied by Boltzmann weighting factors created using heats of formation determined by the AM1 optimizations, the weighted composite CD spectrum created did resemble experiment for the pi-pi* transition indicating that both conformations may exist simultaneously in solution.