Protein stability osmolyte effects

The most commonly used generic term for a dissolved substance is solute, and this is the term that we will employ in most contexts, for both large and small compounds, that is, for macromolecules and micromolecules. A closely related term, cosolvent, is often used by physical chemists when the issue in question involves a dissolved substance that either stabilizes or destabilizes the structures of macromolecules. For instance, cosolvent is often used in literature on the effects of solutes on protein stability. A more restrictive and specific term that will be employed when we discuss the osmotic relationships of organisms is osmolyte. 

D.W. Bolen, Effects of naturally occurring osmolytes on protein stability and solubility issues important in protein crystallization, Methods 34 (2004) 312-322. 

Anton, M., J. R6sgen, M. Sinev, L. M. R Holthanzen, and D. W. Bolen. 2011. Osmolyte effects on protein stability and solubility A balancing act between backbone and side-chains. Biophysical Chemistry. 159, 90. 

Case, E. H., J. Brennan, A. Chaka, K. D. Dobbs, D. G. Eriend, D. Frurip, P. A. Gordon, J. Moore, R. D. Mountain, J. Olson, R. B. Ross, M. Sehiller, and V. K. Shen. 2007. The third industrial fluid properties simulation challenge. Eluid Phase Equilibria. 260, 153. Celinski, S. A. and J. M. Scholtz. 2002. Osmolyte effects on helix formation in peptides and the stability of eoiled-coils. Protein Science. 11, 2048. 

One group of kosmotropic stabilizers of proteins are the osmolytes, organic osmoprotectant solutes, mostly polyhydric alcohols and amino acids or their derivatives. Osmolyte compatibility of organisms is thought to result from absence of osmolyte interactions with substrates and cofactors, and the non-perturbing or favorable effects on macromolecular-solvent interactions (Yancey, 1982). 

Granata V, Palladino P, Tizzano B, Negro A, Berisio R, Zagari A (2006) The effect of the osmolyte trimethylamine N-oxide on the stability of the prion protein at low pH. Biopolymers 82 234... 

Classically we think of osmolyte-induced stability as brought about by a thermodynamically unfavorable interaction with the protein (Lee and Timasheff 1981 Arakawa and Timasheff 1985a). We understand that if we decompose a protein into side chains and backbone that stability induced by such an osmolyte results in correlations or solution fluctuations, which thermodynamically yield a response less favorable than that with water (the osmophobic effect) (Rosgen, Pettitt, and Bolen 2004). Similarly, we consider solution stabilization or protein denaturation as having a substantial component that occurs by favorable interactions with the osmolyte (Pace 1986 Bolen and Baskakov 2001). More recently, it has become clear that the thermodynamics is not overwhelmingly dominated by the interactions with the side chains, but rather the backbone makes a major, perhaps dominant contribution in many cases (Auton, Holthauzen, and Bolen 2007 Auton et al. 2011). The precise nature of the balance is dependent on the concentration of osmolyte as recently shown (Auton et al. 2011) Some less concentrated solutions of osmolyte solutions do not show the backbone contributions as purely dominating the side chains. However, the backbone shows a classically surprising contribution to stability in aU cases the side chains are not responsible alone. 

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