Temperature Dependence of Hydrogen-Bond Stability in β-Hairpin Structures

Abstract

Understanding the temperature effect in the folding of multiple β-hairpins with different sequence (although based on an approximate solution model) makes possible quantitative characterization of the different contributing factors that are difficult to be obtained from single temperature studies. The detailed thermodynamics analyses performed in this article provide at least a semiquantitative understanding of how temperature and positions affect the stability of individual backbone hydrogen bonds in β-hairpin structures. These effects are then rationalized, according to the separation into enthalpic and entropic contributions. The formation of backbone hydrogen bonds at the terminal position is favored at low temperatures and those near the turn become more favorable at high temperatures, as a result of the differences in their formation entropy. Regardless of the differences in the turn stability, the side-chain hydrophobicity, and the room temperature folding mechanism of these β-hairpins, there is a shift to the “zip-out” mechanism in the assembling of backbone hydrogen bonds as temperature increases for all polypeptides under study. In addition, it was also observed that although the backbone hydrogen-bond formation shows a strong dependence on temperature, the formation order of the three structural elements of β-hairpin (the turn, hydrophobic core cluster, and hydrogen-bond assembly) along the minimum free energy pathway in the free energy landscapes appears to be only sequence dependent and largely unaffected by the temperature change.