On the molecular mechanism of stabilization of proteins by cosolvents: role of Lifshitz electrodynamic forces.
Several ionic and nonionic additives are known to affect structural stability of proteins in aqueous solutions. At a fundamental level, the mechanism of stabilization or destabilization of proteins by cosolvents must be related to three-body interactions between the protein, additive, and the water medium. In this study, the role of the Lifshitz-van der Waals electrodynamic interaction between various additives (sucrose, glycerol, urea, poly(ethylene glycol)-200, betaine, taurine, proline, and valine) and bovine serum albumin (BSA) in water medium was examined. The electrodynamic interaction energy was attractive for all of the additives studied here when both far ultraviolet and infrared relaxations of the additives were included in their dielectric susceptibility representations. However, when only the infrared contribution was included for structure stabilizers and both far ultraviolet and infrared contributions for the structure destabilizers, the resulting electrodynamic interaction energy (E/kT) followed the structure stabilizing and/or destabilizing behavior of the additives; that is, the interaction was attractive for urea and PEG200 (structure destabilizers), whereas it was repulsive for sucrose, glycerol, betaine, taurine, alanine, valine, and proline (structure stabilizers). The electrodynamic interaction energy E/kT at any given surface-to-surface separation distance between the additives and BSA was positively correlated (r(2) = 0.92) with the experimental thermal denaturation temperature (T(d)) of BSA in 1 M solutions of the additives. These analyses provided a mechanistic basis for the experimental observations of exclusion of the structure-stabilizing additives from the protein-water interface and binding of the structure-destabilizing additives to the protein surface. The role of water structure in the three-body electrodynamic interaction is discussed. It is hypothesized that in the case of additives that enhance water structure the hydration shells formed around the additives effectively dampen the contribution of ultraviolet frequencies to the dielectric susceptibility of the additives and thus impart repulsive electrodyanamic interaction between the additive and the protein, whereas the opposite occurs in the case of additives that breakdown the hydrogen-bonded structure of water.
Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States. sdamodar@wisc.edu
Srinivasan
S
Damodaran
D000409:Alanine / Q000737:chemistry; D000818:Animals; D002417:Cattle; D004583:Electrons; D005990:Glycerol / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D055550:Protein Stability; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D012997:Solvents; D014867:Water; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D013395:Sucrose; D000409:Alanine; D005990:Glycerol