Helix propagation and N‐cap propensities of the amino acids measured in alanine‐based peptides in 40 volume percent trifluoroethanol

• Published in: Protein science Vol. 5; no. 12; pp. 2623 - 2637
• Main Authors: Rohl, Carol A., Chakrabartty, Avijit, Baldwin, Robert L.
• Format: Journal Article
• Language: English
• Published: Bristol Cold Spring Harbor Laboratory Press 01.12.1996
• Subjects: Alanine - chemistry; alanine‐based peptides; Amino Acid Sequence; helix propensities; helix‐breaking amino acids; Molecular Sequence Data; N‐cap propensities; Peptides - chemistry; Protein Folding; Trifluoroethanol
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1002/pro.5560051225

The helix propagation and N‐cap propensities of the amino acids have been measured in alanine‐based peptides in 40 volume percent trifluoroethanol (40% TFE) to determine if this helix‐stabilizing solvent uniformly 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 redefining the capping statistical weights and evaluating the helix nucleation constant with N‐capping explicitly included in the helix‐coil model. The propagation propensities of all amino acids increase in 40% TFE relative to water, but the increases are highly variable. In water, all β‐branched and β‐substituted amino acids are helix breakers. In 40% TFE, the propagation propensities of the nonpolar amino acids increase greatly, leaving charged and neutral polar, β‐substituted amino acids as helix breakers. Glycine and proline are strong helix breakers in both solvents. Free energy differences for helix propagation (ΔΔG) between alanine and other nonpolar amino acids are twice as large in water as predicted from side‐chain conformational entropies, but ΔΔG values in 40% TFE are close to those predicted from side‐chain entropies. This dependence of ΔΔG on the solvent points to a specific role of water in determining the relative helix propensities of the nonpolar amino acids. The N‐cap propensities converge toward a common value in 40% TFE, suggesting that differential solvation by water contributes to the diversity of N‐cap values shown by the amino acids.