Ca. Rohl et al., HELIX PROPAGATION AND N-CAP PROPENSITIES OF THE AMINO-ACIDS MEASURED IN ALANINE-BASED PEPTIDES IN 40 VOLUME PERCENT TRIFLUOROETHANOL, Protein science, 5(12), 1996, pp. 2623-2637
The helix propagation and N-cap propensities of the amino acids have b
een measured in alanine-based peptides in 40 volume percent trifluoroe
thanol (40% TFE) to determine if this helix-stabilizing solvent unifor
mly affects all amino acids. The propensities in 40% TFE are compared
with revised values of the helix parameters of alanine-based peptides
in water. Revision of the propensities in water is the result of redef
ining the capping statistical weights and evaluating the helix nucleat
ion constant with N-capping explicitly included in the helix-coil mode
l. The propagation propensities of all amino acids increase in 40% TFE
relative to water, but the increases are highly variable. In water, a
ll beta-branched and beta-substituted amino acids are helix breakers.
In 40% TFE, the propagation propensities of the nonpolar amino acids i
ncrease greatly, leaving charged and neutral polar, beta-substituted a
mino acids as helix breakers. Glycine and proline are strong helix bre
akers in both solvents. Free energy differences for helix propagation
(Delta Delta G) between alanine and other nonpolar amino acids are twi
ce as large in water as predicted from side-chain conformational entro
pies, but Delta Delta G values in 40% TFE are close to those predicted
from side-chain entropies. This dependence of Delta Delta G on the so
lvent points to a specific role of water in determining the relative h
elix propensities of the nonpolar amino acids. The N-cap propensities
converge toward a common value in 40% TFE, suggesting that differentia
l solvation by water contributes to the diversity of N-cap values show
n by the amino acids.