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

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.     

Effects of surfactants on wave-induced drainage of foam and emulsion films

It is well established that the plane-parallel models of foam and emulsion films underestimate the velocity of film thinning by up to several orders of magnitude and show an incorrect dependence of thinning velocity on film radius. A new theory of film thinning has been previously formulated for tangentially immobile films [12, 13], and shows that the reason for this discrepancy is the neglect of experimentally observed finite amplitude surface waves. For thin films of relatively large radii (> 1o^–2 cm), the pumping of the fluid generated by oscillations of the surface waves, provides the dominant contribution to film thinning velocity. The present hydrodynamic model includes the effects of surfactants (Marangoni-Gibbs-effect, surface viscosity and surface diffusion) and surface waves on thinning velocity. As in the case of a tangentially immobile film, it is concluded that the thinning velocity varies inversely with less than the first power of the film radius, and not with the square of the film radius, as predicted by the plane-parallel models of thin film. Also, the velocity of thinning is found to be up to several orders of magnitudes larger than that evaluated from the plane-parallel models. The influence of waves in enhancing the thinning velocity is found to be most significant for a tangentially immobile film and this effect decreases by a factor of up to 3, with a decrease in surface elasticity and surface viscosity.     

On the interactions of ions with the air/water interface

In the vicinity of a charged interface, the Poisson-Boltzmann approach considers that the ions obey Boltzmann distributions in a mean electrical field that satisfies the Poisson equation. However, the boundary between two dielectrics generates additional interactions between ions and the interface. The traditional models of ion hydration interactions, that assume that water is a homogeneous dielectric, predict that these interactions are repulsive for all kinds of ions, since all ions should prefer the medium with a larger dielectric constant, where they are better hydrated. In reality, the interactions between the ions and the neighboring water molecules can generate additional short-range ion-hydration interactions, which are either repulsive (for structure-making ions) or attractive (for structure-breaking ions). In the present paper, various models for the ion-hydration forces are examined and compared with the results of molecular dynamics simulations. At large ionic strengths, the latter results could be reproduced qualitatively only when short-ranged attractions between the structure-breaking ions and the interface were taken into account.     

Attractive interactions in dispersions of identical charged colloidal particles: a Monte Carlo simulation

Using the Debye-Hückel pair potential, the collective interactions between identical charged particles were examined via Monte Carlo simulations. The results have shown that when the number of charges per particle and the particle volume fraction were sufficiently large, the pair long-range electrostatic repulsion generated an effective attractive interaction between identical charged particles because of many-body effects. Disordered liquid-like structures, ordered crystal-like structures, ordered structures dispersed in disordered ones, and disordered structures dispersed in ordered ones have been found. The structures are dependent on the volume fraction and charge of the particles, as well as on the electrolyte concentration.     

Temperature effects on the nucleation mechanism of protein folding and on the barrierless thermal denaturation of a native protein

Recently, the authors proposed a kinetic model for the nucleation mechanism of protein folding where a protein was treated as a heteropolymer with all the bonds and bond angles equal and constant. As a crucial idea of the model, an overall potential around a cluster of native residues in which a protein residue performs a chaotic motion is considered to be a combination of three potentials: effective pairwise, average dihedral, and confining. The overall potential as a function of the distance from the cluster center has a double well shape which allows one to determine the rates with which the cluster emits and absorbs residues by using a first passage time analysis. One can then develop a kinetic theory for the nucleation mechanism of protein folding and evaluate the protein folding time. In the present paper we evaluate the optimal temperature at which the protein folding time is the shortest. A method is also proposed to determine the temperature dependence of the folding time without carrying out the time consuming calculations for a series of temperatures. Using Taylor series expansions in the formalism of the first passage time analysis, one can calculate the temperature dependence of the cluster emission and absorption rates in the vicinity of some temperature T(0) if they are known at T(0). Thus one can evaluate the protein folding time t(f) at any other temperature T in the vicinity of T(0) at which the folding time t(f) is known. We also present a model for the thermal denaturation of a protein occurring via the decay of the native structure of the protein. Due to a sufficiently large temperature increase or decrease, the rate with which a cluster of native residues within a protein emits residues becomes larger than the absorption rate in the whole range of cluster sizes up to the size of the whole protein. This leads to the unfolding of the protein in a barrierless way, i.e., as spinodal decomposition. Knowing the cluster emission and absorption rates as functions of temperature and cluster size, one can find the threshold temperatures of cold and hot barrierless denaturation as well as the corresponding unfolding times. Both proposed methods are illustrated by numerical calculations for two model proteins, one consisting of 124 amino acids, the other consisting of 2500 residues. The first one roughly mimicks a bovine pancreatic ribonuclease while the second one is a representative of the largest proteins which are extremely difficult to study by straightforward Monte Carlo or molecular dynamics simulations.     

Excess around a central molecule with application to binary mixtures

It was shown by us (J. Phys. Chem. B, 2006, 110, 12707) that the excess (deficit) of any species i around a central molecule j in a binary mixture is not provided by c(i)G(ij) (where c(i) is the molar concentration of species i in the mixture and G(ij) are the Kirkwood-Buff integrals) as usually considered and that an additional term, involving a volume V(j) which is inaccessible to molecules of species i because of the presence of the central molecule j, must be included. In this paper, the new expression is applied to various binary mixtures and used to establish a simple criterion for preferential solvation in a binary system. First, it is applied to binary Lennard-Jones fluids. The conventional expression for the excess (deficit) in binary mixtures, c(i)G(ij), provides always deficits around any central molecule in such fluids. In contrast, the new expression provides excess for one species and deficit for the other one. In addition, two kinds of binary mixtures involving weak (argon/krypton) and strong (alcohols/water) intermolecular interactions were considered. Again, the conventional expression for the excess (deficit) in a binary mixture, c(i)G(ij), provides always deficits for any central molecule in the argon/krypton mixture, whereas the new expression provides excess for argon (a somewhat smaller molecule) and deficit for krypton. Three alcohol/water binary mixtures (1-propanol/water, tert-butanol/water and methanol/water) with strong intermolecular interactions were considered and compared with the available experimental information regarding the molecular clustering in solutions. We found (for 1-propanol/water and tert-butanol/water) a large excess of alcohols around a central alcohol molecule and a large excess of water around a central water molecule. For both mixtures the maximum of the calculated excess with respect to the concentration corresponds to the maximum in the cluster size found experimentally, and the range of alcohol concentrations in which the calculated excess becomes very small corresponds to the composition range in which no clusters could be identified experimentally.     

Two-dimensional symmetry breaking of fluid density distribution in closed nanoslits

Stable and metastable fluid density distributions (FDDs) in a closed nanoslit between two identical parallel solid walls have been identified on the basis of a nonlocal canonical ensemble density functional theory. Similar to Monte Carlo simulations, periodicity of the FDD in one of the lateral (parallel to the walls surfaces) directions, denoted as the x direction, was assumed. In the other lateral direction, y direction, the FDD was considered uniform. It was found that depending on the average fluid density in the slit, both uniform as well as nonuniform FDDs in the x direction can occur. The uniform FDDs are either symmetric or asymmetric about the middle plane between walls; the latter FDD being the consequence of a symmetry breaking across the slit. The nonuniform FDDs in the x direction occur either in the form of a bump on a thin liquid film covering the walls or as a liquid bridge between those walls and provide symmetry breaking in the x direction. For small and large average densities, the stable state is uniform in the x direction and is symmetric about the middle plane between walls. In the intermediate range of the average density and depending on the length L(x) of the FDD period, the stable state can be represented either by a FDD, which is uniform in the x direction and asymmetric about the middle of the slit (small values of L(x)), or by a bump- and bridgelike FDD for intermediate and large values of L(x), respectively. These results are in agreement with the Monte Carlo simulations performed earlier by other authors. Because the free energy of the stable state decreases monotonically with increasing L(x), one can conclude that the real period is very large (infinite) and that for the values of the parameters employed, a single bridge of finite length over the entire slit is generated.     

Symmetry breaking in binary mixtures in closed nanoslits

The symmetry breaking (SB) of the fluid density distribution (FDD) in closed nanoslits between two identical parallel solid walls described by Berim and Ruckenstein [J. Chem. Phys. 128, 024704 (2008)] for a single component fluid is examined for binary mixtures on the basis of a nonlocal canonical ensemble density functional theory. As in Monte Carlo simulations, the periodicity of the FDD in one of the lateral (parallel to the wall surfaces) directions, denoted as the x direction, was assumed. In the other lateral direction, y direction, the FDD was considered to be uniform. The molecules of the two components have different diameters and their Lennard-Jones interaction potentials have different energy parameters. It was found that depending on the average fluid density in the slit and mixture composition, SB can occur for both or none of the components but never for only one of them. In the direction perpendicular to the walls (h direction), the FDDs of both components can be asymmetrical about the middle plane between walls. In the x direction, the SB occurs as bumps and bridges enriched in one of the components, whereas the composition of the mixture between them is enriched in the other component. The dependence of the SB states on the length Lx of the FDD period at fixed average densities of the two components was examined for Lx in the range from 10 to 120 molecular diameters of the smaller size component. It was shown that for large Lx, the stable state of the system corresponds to a bridge. Because the free energy of that state decreases monotonically with increasing Lx, one can conclude that the real period is very large (infinite) and that a single bridge exists in the slit.