The Kirkwood–Buff theory and the effect of cosolvents on biochemical reactions

Abstract

Cosolvents added to aqueous solutions of biomolecules profoundly affect protein stability, as well as biochemical equilibria. Some cosolvents, such as urea and guanidine hydrochloride, denature proteins, whereas others, such as osmolytes and crowders, stabilize the native structures of proteins. The way cosolvents interact with biomolecules is crucial information required to understand the cosolvent effect at a molecular level. We present a statistical mechanical framework based upon Kirkwood-Buff theory, which enables one to extract this picture from experimental data. The combination of two experimental results, namely, the cosolvent-induced equilibrium shift and the partial molar volume change upon the reaction, supplimented by the structural change, is shown to yield the number of water and cosolvent molecules bound or released during a reaction. Previously, denaturation experiments (e.g., m-value analysis) were analyzed by empirical and stoichiometric solvent-binding models, while the effects of osmolytes and crowders were analyzed by the approximate molecular crowding approach for low cosolvent concentration. Here we synthesize these previous approaches in a rigorous statistical mechanical treatment, which is applicable at any cosolvent concentration. The usefulness and accuracy of previous approaches was also evaluated.

Recent Applications of Kirkwood–Buff Theory to Biological Systems

“…Simultaneously, Smith and Shimizu applied KB theory to understand cosolvent mediated protein denaturation and protein stability by osmolytes [42,54,83,84,105]. Shimizu and coworkers have used KB theory to determine hydration changes for allosteric transitions and ligand binding, and to clarify the assumptions made in osmotic stress analysis [54,84,96,103,105].…”

“…Shimizu and coworkers have used KB theory to determine hydration changes for allosteric transitions and ligand binding, and to clarify the assumptions made in osmotic stress analysis [54,84,96,103,105]. Smith outlined a rigorous link between the results of computer simulations and the corresponding experimental thermodynamic data [42,83].…”

Experimental triplet and quadruplet fluctuation densities and spatial distribution function integrals for liquid mixtures

“…29,[37][38][39][40][41][42][43] Under isothermal conditions, the second derivatives in the GCE only involve the particle number fluctuations between all possible pairs of species. These fluctuations are then related to second derivatives of the Gibbs free energy for an equivalent closed system.…”

Preferential interaction parameters in biological systems by Kirkwood–Buff theory and computer simulation

“…[9][10][11][12][13] The use of KB theory is particularly well suited for the analysis of experimental data as it involves no approximations, and for the analysis of simulation data as it only requires the determination of radial distribution functions (rdfs), or coordination numbers, which are easily obtained from simulations. Our previous studies have involved using KB theory to improve the force fields required for computer simulation, [14][15][16][17][18][19] relating simulation data on cosolvent effects to experimental thermodynamic data, [10,11,20,21] and for the interpretation of thermodynamic data on cosolvent effects on biomolecules.…”