Protein-Osmolyte interactions: Molecular insights

Abstract

Osmolytes, small molecular weight organic molecules, are capable of maintaining structural and functional integrity of macromolecules. It has been known that osmolytes help to protect functional integrity of proteins by increasing their thermodynamic stability and inducing folding of unstable or misfolded proteins. The mechanism of osmolyte-protein interaction has been studied in detail and significant progresses have been so far made. Thermodynamically, osmolytes increase the stability of proteins by affecting the thermodynamic equilibrium, native conformation ↔ denatured conformation toward the left. For this, osmolytes interact with proteins through various forces to affect this thermodynamic equilibrium. Most osmolytes stabilize or induce protein folding by means of preferential hydration effect. Main driving force for the preferential hydration effect of osmolytes is due to their unfavorable interaction with the peptide backbone. In contrast to the osmophobic effect, few osmolytes (e.g., polyols) are also known to stabilize proteins due to solvophobic effect. Several mathematical models have also been developed that can well explain the atomic level interaction between the protein and osmolyte molecule. In this review we have systematically reviewed all major forces involved in osmolyte-protein interactions.