Thermodynamic Fingerprints Reveal Variability in Cosolute Effect on Peptide Folding

Abstract

On the molecular level, life is established through the specific interaction between and within macromolecules in an aqueous environment. It is increasingly realized, however, that even modest changes in solution conditions, brought on by the presence of many cellular cosolutes, can profoundly affect the balance of forces underlying the specificity of interaction, with consequences that can be severe if not fatal. We have followed the thermodynamic effect of several cosolute classes, including polymers, cellular osmolytes, and inorganic salts, on the stability of peptide folding. By comparing changes in free energy, enthalpy, and entropy upon cosolute addition for this process, we identify several thermodynamically distinct mechanisms. Surprisingly, even while many cosolutes display similar linear scaling of the free energy with cosolute concentration, a breakdown of this free energy into enthalpic and entropic contributions distinguishes between different families of cosolutes. We show how these “thermodynamic fingerprints” can be used to group distinct cosolute families, and to suggest the existence of different mechanisms by which members of these families act.Sukenik S, Sapir L, Gilman-Politi R, Harries D (2012) Diversity in the mechanisms of cosolute action on biomolecular processes Faraday Disc. 106 doi: 10.1039/C2FD20101A