Interaction between water and polar groups of the helix backbone: an important determinant of helix propensities.

Abstract

We report an enthalpic factor involved in determining helix propensities of nonpolar amino acids. Thermal unfolding curves of the five 13-residue peptides, Ac-KA4XA4KGY-NH2 (X = Ala, Leu, Ile, Val, Gly), have been measured by using CD in water/trifluoroethanol (TFE) mixtures. The peptide helix contents show that the rank order of helix propensities changes with temperature: although Ala has the highest helix propensity at 0 degrees C in all TFE concentrations, it is lower than Leu, Ile, and Val at 50 degrees C in 20% TFE. This change is attributed to shielding by nonpolar side chains of the interaction between water and polar groups in the helix backbone for the following reasons. (i) Helix content is directly related to helix propensity for these designed peptides because side-chain-side-chain interactions are absent. (ii) The change in rank order with temperature is enthalpic in origin: in water, the apparent enthalpy of helix formation calculated from the thermal unfolding curves varies widely among the five peptides and has the same rank order as the helix propensities at 0 degrees C. The rank order does not result from burial of nonpolar surface area because the calculated heat capacity change (DeltaCp) on helix formation is opposite in sign from the expected DeltaCp. (iii) A nonpolar side chain can exclude water from interacting with helix polar groups, according to calculations of water-accessible surface area, and the polar interaction between water and peptide polar groups is entirely enthalpic, as shown by amide transfer data.