α- and 3₁₀-Helix Interconversion: A Quantum-Chemical Study on Polyalanine Systems in the Gas Phase and in Aqueous Solvent

Abstract

Helices are among the predominant secondary structures in globular proteins. About 90% of the residues in them are found to be in the α-helical conformation, and another 10% in the 310 conformation. There is a standing controversy between experimental and some theoretical results, and controversy among theoretical results concerning the predominance of each conformation, in particular, helices. We address this controversy by ab initio Hartree−Fock and density functional theory studies of helices with different lengths in a vacuum and in the aqueous phase. Our results show that (1) in a vacuum, all oligo(Ala) helices of 4−10 residues adopt the 310 − conformation; (2) in aqueous solution, the 6−10 residue peptides adopt the α-helical conformation; (3) there might be two intermediates between these helical conformers allowing for their interconversion. The relevance of these results to the structure and folding of proteins is discussed.