Effect of the environment and role of the pi-pi stacking interactions in the stabilization of the 3(10)-helix conformation in dehydroalanine oligopeptides.

A quantum-mechanical study of the chain-length dependent stability of the extended, 2(7)-ribbon and 3(10)-helix conformations in dehydroalanine (delta Ala) oligopeptides has been performed. To address the study, the oligopeptides delta Ala(n), where n varies from 1 to 6, were computed by using the semiempirical AMI methodology. Cooperative free-energy effects permit one to predict the stabilization of the 3(10)-helix with respect to the extended and 2(7)-ribbon conformations when the number of residues in the polypeptide chain increases. The interactions associated with the pi-electron density of the side chains can easily explain this finding. The effects of the solvent and the crystalline packing on the different conformations were modeled using a self-consistent reaction field (SCRF) method and a molecular mechanics approach to the packing, respectively. Both the aqueous and crystal environments seem to be a key factor in the stabilization of the helical conformation. Finally, the variations of electrostatic parameters such as atomic point charges and dipole moments in delta Ala-containing peptides with internal (conformation) and external (solvent) effects are discussed.