A protein molecule in an aqueous mixed solvent: Fluctuation theory outlook

Abstract

In the present paper a procedure to calculate the properties of proteins in aqueous mixed solvents, particularly the excesses of the constituents of the mixed solvent near the protein molecule and the preferential binding parameters, is suggested. Expressions for the Kirkwood-Buff integrals in ternary mixtures and for the preferential binding parameter were derived and used to calculate various properties of infinitely dilute proteins in aqueous mixed solvents. The derived expressions and experimental information regarding the partial molar volumes and the preferential binding parameters were used to calculate the excesses (deficits) of water and cosolvent (in comparison with the bulk concentrations of protein-free mixed solvent) in the vicinity of ribonuclease A, ribonuclease T1, and lysozyme molecules. The calculations showed that water was in excess in the vicinity of ribonuclease A for water/glycerol and water/trehalose mixtures, and the cosolvent urea was in excess in the vicinity of ribonuclease T1 and lysozyme. The derivative of the activity coefficient of the protein with respect to the mole fraction of water was also calculated. This derivative was negative for the water/glycerol and water/trehalose mixed solvents and positive for the water/urea mixture. The mixture of lysozyme in the water/urea solvent is of particular interest, because the lysozyme at pH 7.0 is in its native state up to 9.3M urea, while at pH 2.0 it is denaturated between 2.5 and 5M and higher concentrations of urea. Our results demonstrated a striking similarity in the hydration of lysozyme at both pHs. It is worthwhile to note that the excesses of urea were only weakly composition dependent on both cases.

Molecular Level Probing of Preferential Hydration and Its Modulation by Osmolytes through the Use of Pyranine Complexed to Hemoglobin

“…The above argument predicts that urea and high charge density cations such as Mg 2ϩ should accumulate in the less polar hydration layers of the protein relative to the bulk solvent as previously concluded based on calculations (50). As a result, the hydration layer relative to the bulk should experience an enhanced impact of adding urea or Mg 2ϩ .…”

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.…”

Kirkwood–Buff theory of four and higher component mixtures

“…29,30 This can be quite tedious. Recently, we suggested starting from expressions for the fully open system and transforming to the required ensemble in a stepwise manner.…”