HELIX PROPAGATION AND N-CAP PROPENSITIES OF THE AMINO-ACIDS MEASURED IN ALANINE-BASED PEPTIDES IN 40 VOLUME PERCENT TRIFLUOROETHANOL

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.