A. Chakrabartty et al., HELIX PROPENSITIES OF THE AMINO-ACIDS MEASURED IN ALANINE-BASED PEPTIDES WITHOUT HELIX-STABILIZING SIDE-CHAIN INTERACTIONS, Protein science, 3(5), 1994, pp. 843-852
Helix propensities of the amino acids have been measured in alanine-ba
sed peptides in the absence of helix-stabilizing side-chain interactio
ns. Fifty-eight peptides have been studied. A modified form of the Lif
son-Roig theory for the helix-coil transition, which includes helix ca
pping (Doig AJ, Chakrabartty A, Klingler TM, Baldwin RL, 1994, Biochem
istry 33:3396-3403), was used to analyze the results. Substitutions we
re made at various positions of homologous helical peptides. Helix-cap
ping interactions were found to contribute to helix stability, even wh
en the substitution site was not at the end of the peptide. Analysis o
f our data with the original Lifson-Roig theory, which neglects cappin
g effects, does not produce as good a fit to the experimental data as
does analysis with the modified Lifson-Roig theory. At 0 degrees C, Al
a 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 i
s that formation of peptide H-bonds can largely offset the unfavorable
entropy change caused by fixing the peptide backbone. The helix prope
nsities of most amino acids oppose folding; consequently, the majority
of isolated helices derived from proteins are unstable, unless specif
ic side-chain interactions stabilize them.