title: Large differences in the helix propensities of alanine and glycine.
abstract: The standard view of alpha helix formation in water, based on helix propensities determined by the host-guest method, is that differences in helix propensity among the amino acids are small, except for proline, and that the average value of the helix propagation parameter s is near 1. A contradictory view of alpha helix formation in water is emerging from substitution experiments with short, unique-sequence peptides that contain only naturally occurring amino acids. Short peptides that contain only alanine and lysine, or alanine and glutamate, form surprisingly stable monomeric helices in water and substitution of a single alanine residue by another amino acid in these or related peptides produces a wide range of changes in helix content, depending on which amino acid is substituted for alanine. We show here that the ratio of the helix propensities of alanine to glycine is large, about 100, in substitution experiments with a 17-residue reference peptide containing alanine and lysine. The helix propensity is identified with s, the helix propagation parameter of the statistical mechanics model for alpha helix formation, and the results are interpreted by the Lifson-Roig theory. Single alanine----glycine substitutions have been made at a series of positions in individual peptides. The helix-destabilizing effect of an Ala----Gly substitution depends strongly on its position in the helix, as predicted by the Lifson-Roig theory if the ratio of s values for Ala:Gly is large.
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, California 94305.
authors.forename: A
authors.initials: A
authors.lastname: Chakrabartty
authors.forename: J A
authors.initials: JA
authors.lastname: Schellman
authors.forename: R L
authors.initials: RL
authors.lastname: Baldwin
mesh_terms: D000409:Alanine / Q000737:chemistry*; D000595:Amino Acid Sequence; D005998:Glycine / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014867:Water
chemical_list: D010455:Peptides; D014867:Water; D000409:Alanine; D005998:Glycine