Protein Science, Vol 3, Issue 5 843-852, Copyright © 1994 by Cold Spring Harbor Laboratory Press

ARTICLE

Helix propensities of the amino acids measured in alanine-based peptides without helix-stabilizing side-chain interactions

A. CHAKRABARTTY, T. KORTEMME and R. L. BALDWIN
Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305

Helix propensities of the amino acids have been measured in alanine-based peptides in the absence of helix-stabilizing side-chain interactions. Fifty-eight peptides have been studied. A modified form of the Lifson-Roig theory for the helix-coil transition, which includes helix capping (Doig AJ, Chakrabartty A, Klingler TM, Baldwin RL, 1994, Biochemistry 33:3396-3403), was used to analyze the results. Substitutions were made at various positions of homologous helical peptides. Helix-capping interactions were found to contribute to helix stability, even when the substitution site was not at the end of the peptide. Analysis of our data with the original Lifson-Roig theory, which neglects capping effects, does not produce as good a fit to the experimental data as does analysis with the modified Lifson-Roig theory. At 0{deg}C, Ala is a strong helix former, Leu and Arg are helix-indifferent, and all other amino acids are helix breakers of varying severity. Because Ala has a small side chain that cannot interact significantly with other side chains, helix formation by Ala is stabilized predominantly by the backbone (``peptide H-bonds''). The implication for protein folding is that formation of peptide H-bonds can largely offset the unfavorable entropy change caused by fixing the peptide backbone. The helix propensities of most amino acids oppose folding; consequently, the majority of isolated helices derived from proteins are unstable, unless specific side-chain interactions stabilize them.
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