Osmolytes are small organic compounds that affect protein stability and are ubiquitous in living systems. In the equilibrium protein folding reaction, unfolded (U) native (N), protecting osmolytes push the equilibrium toward N, whereas denaturing osmolytes push the equilibrium toward U. As yet, there is no universal molecular theory that can explain the mechanism by which osmolytes interact wit...

Examining solute-induced changes in protein conformational equilibria is a long-standing method for probing the role of water in maintaining protein stability. Interpreting the molecular details governing the solute-induced effects, however, remains controversial. We present experimental and theoretical data for osmolyte-induced changes in the stabilities of the A and N states of yeast iso-1-fe...

Osmolytes are low molecular weight organic molecules accumulated by organisms to assist proper protein folding, and to provide protection to the structural integrity of proteins under denaturing stress conditions. It is known that osmolyte-induced protein folding is brought by unfavorable interaction of osmolytes with the denatured/unfolded states. The interaction of osmolyte with the native st...

An all-atom Gō model of Trp-cage protein is simulated using discontinuous molecular dynamics in an explicit minimal solvent, using a single, contact-based interaction energy between protein and solvent particles. An effective denaturant or osmolyte solution can be constructed by making the interaction energy attractive or repulsive. A statistical mechanical equivalence is demonstrated between t...

It is well-known that the typical protein’s three-dimensional structure is relatively unstable in harsh conditions. A practical approach to maintain the folded state and thus improve the stability and activity of proteins in unusual circumstances is to directly apply stabilizing substances such as osmolytes to the protein-containing solutions. Osmolytes as natural occurring organic molecules ty...

Virtually all taxa use osmolytes to protect cells against biochemical stress. Osmolytes often occur in mixtures, such as the classical combination of urea with TMAO (trimethylamine N-oxide) in cartilaginous fish or the cocktail of at least six different osmolytes in the kidney. The concentration patterns of osmolyte mixtures found in vivo make it likely that synergy between them plays an import...

Osmolytes are small organic solutes produced by the cells of all organisms (except halobacteria) in high stress situations (e.g. extremes of salt concentration, high temperature, etc.) to stabilize their macromolecules and so conserve biological activity. They do not interact with the macromolecule directly but act by altering the solvent properties in the cellular environment, and so their pre...

The IR absorption and time-resolved IR spectroscopy of the OD stretch mode of HDO in water was successfully used to study osmolyte effects on water H-bonding network. Protecting osmolytes such as sorbitol and trimethylglycine (TMG) make the vibrational OD stretch band red-shifted, whereas urea affects the OD band marginally. Furthermore, we recently showed that, even though sorbitol and TMG cau...