Solubilized, spaced polyalanines: a context-free system for determining amino acid alpha-helix propensities

Abstract

The logical design principles behind a system of properly water-solubilized, spaced polyalanines are presented. Peptides conforming to these design principles are shown to be unaggregated, and their helical properties as measured by the circular dichroism (CD) residue ellipticity at 222 nm, [theta](222), are shown to be dependent upon the lengths of their alanine regions. It is further demonstrated that CD contributions of the alanine cores are independent of the CD contributions attributable to other features of the peptides. The CD response of these polyalanines to variations in temperature and salt or denaturant concentration is described. CD data for a series of peptides with Ala(n) cores varying in length from 12 to 45 residues are presented that allow calculation of the helical propensity, w(Ala), in a purely alanine context. Mathematical modeling of these unprecedented data reveals the insufficiency of currently accepted literature helicity modeling parameters. A modification to the standard Lifson-Roig algorithm is introduced based on hydrogen-bonding cooperativity.