Why does salt increase hydrophobic interactions

The correlation functions suggest that the water structure in all four systems is very similar to bulk water. There is no evidence of structural enhancement in going from pure water to water in the alc. There is a small but probably significant increase in structure in the tetraalkylammonium bromide solns. There is very little measurable difference between the two alc. The results are consistent with the view that apolar solutes are located in the cavities in the hydrogen-bonded water network, but they suggest that the increase in order assocd.

The Interatomic Structure of Argon in Water. The first order difference method of neutron diffraction and isotopic substitution NDIS has been applied to argon dissolved under pressure in heavy water. The results show that argon atoms possess a well-defined nearest neighbor hydration shell composed of 16 2 water mols.

The results are in broad agreement with those obtained from Monte Carlo and M. Significant differences are discernible when attempts are made to match quant. Hydrophobic Hydration of Methane. There is generally good agreement between these observations and those obtained from the theor. However, it is clear that the model calcns. The volumetric properties of the vapor mixts. The values cover temps. The low-pressure compression measurements were used to det.

The parameters in the square-well potential are derived from virial coeffs. We model the aq. We use a simplified statistical mech. This model has previously been shown to predict qual. We find a very different mechanism for the aq. Small solute transfer involves a large hydrophobic heat capacity; its disaffinity for cold water room temp. In contrast, transferring large nonpolar solutes into water involves no such large changes in heat capacity or entropy.

In this regard, large nonpolar solutes are not "hydrophobic"; their solvation follows classical regular soln. Putting a large nonpolar surface into water breaks hydrogen bonds at all temps. Therefore, the traditional "iceberg" model that first-shell water structure melts out with temp. A key conclusion is that hydrophobicity depends not only on the surface area of a solute but also on its shape and curvature.

The thermodynamic properties of hydrophobic bonds in proteins. A treatment of the thermodynamic properties of hydrophobic bonds in proteins is presented, based on the behavior of aq. The thermodynamic parameters are derived from a statistical thermodynamic treatment of pure water and of aq.

The conditions detg. The latter restriction is less serious than for side-chain H bonding. Numerical values and closed expressions for the temp. The contributions of cystine and tryptophan are estd. The dependence of the thermodynamic parameters on the size of the side chains and on the extent of contact between them is discussed, and the limiting values of the possible ranges are given. The existence of hydrophobic bonds is due mainly to the entropy change connected with changes in the water structure around the side chains.

The endothermicity of formation of hydrophobic bonds makes them stronger with increasing temp. The thermodynamic parameters characterizing isolated side chains are affected only slightly in structures where there are few water layers between side chains not in contact.

The free energy of formation of the hydrophobic bond can be attributed almost entirely to the step in which the two side chains actually come into contact, reducing the no. Hydrophobic bonds can contribute to the stabilization of various protein structures. Such bonds can exist in the random coil. Strong hydrophobic bonds between side chains are possible in the two pleated sheet structures. In compactly folded protein structures, several side chains can interact simultaneously to form hydrophobia bonds or hydrophobic regions, of greater strength.

Expressions are given for the calcn. Nonpolar side chains carrying polar end groups can participate in hydrophobic bonding to a limited extent. The parameters for such bonds are estd. An estimate of the vol. Structure of Water and Hydrophobic Bonding in Proteins.

Model for the thermodynamic properties of aqueous solutions of hydrocarbons. The net intermol. The differences are reflected in a change of the coordination no. As a result, the amt. The H-bonded clusters extend around part of the solute mol. The contribution of the solute to the free energy is estd. Pair versus Bulk Hydrophobic Interactions. The temp. A large computational effort approx. At K assocn. Both internal energy and entropy change sign within this temp. The results correspond qual.

The second osmotic virial coeffs. Agreement with osmotic virial coeffs. The results indicate that pairwise hydrophobic assocn. At present, there is no evidence for a qual. It is demonstrated that the comparison of the second osmotic virial coeff.

American Institute of Physics. The assocn. Convergence of the calcns. Coulomb interactions were treated with the Ewald method. By using this computationally expensive approach many of the previously reported discrepancies in the temp. A temp. Raising temp. The most pronounced temp.

On the Size Dependence of Hydrophobic Hydration. The soly. This puzzling exptl. No real explanation of the phenomenon exists, even though it has been suggested that it is evidence of clathrate-type structure formation around nonpolar mols. In this paper, we show that the exptl. A fundamental ingredient of this theory is the demonstration that the purely structural reorganization of H-bonds in the hydration shell of a nonpolar solute is a compensating process. The work of cavity creation is dominant, detg.

However, for noble gases, on increasing the hard-sphere diam. On the contrary, for aliph. The exptl. Dilute Aqueous Solution of Methane.

Dilute aqueous solution of methane. A Monte Carlo simulation of a dil. The CH4-water pair potential energy function developed for the calcns. The model satisfactorily reproduces the exptl. Interactions between water mols. The computed CH4 coordination no. Hydration of Inert Solutes.

A Molecular Dynamics Study. A molecular dynamics study. The use of a high-speed array processor permitted very long 70 ps simulations of systems of mols.

Structural reorganization within the shells surrounding the solutes and a small degree of slowing down of the mol. The question of whether a solvent-induced hydrophobic attraction exists between the nonpolar solutes was also examd. Hydrophobic interactions are studied by mol. Recently the authors reported a computer simulation calcn. Here this method is compared with 2 other general methods for the calcn. The calcd.

Solute contact configurations are of greater importance than solvent-sepd. In some cases, this conflict may be understood in terms of differences in the assumed, model intermol. CH4 solns. Comparison of the results obtained from the 2 sets of calcns. But its most remarkable influence by far is on the CH4-CH4 potential of mean force; addn.

Polarizable water models thus appear to yield an improved phys. Monte Carlo simulations have been carried out on solns. At all pressures, hydration-shell water mols.

In both the hydration shell and the bulk, the rise of pressure produces an increase in the no. Enhanced structuring of the hydration-shell water mols. At low pressures, a weak second hydration shell around methane develops, and only at higher pressures does it become increasingly significant. Independent results from test particle insertion and free energy perturbation are compared to ensure that zero-PMF baselines are accurate. PMFs are computed under atm. Heat capacity changes upon assocn.

The magnitude of the heat capacity change upon contact formation is much smaller than that predicted by the solvent accessible surface area SASA. More surprisingly, the heat capacity change upon bringing two methanes from infinity to the desolvation barrier is large and pos. This implies that the thermodn. This feature is not predicted by either SASA or a vol. The implications of these and other observations on implicit-solvent model potentials are discussed.

Formulations based on thermodn. In particular, we provide a theor. We report results on the pressure effects on hydrophobic interactions obtained from mol. A wide range of pressures that is relevant to pressure denaturation of proteins is investigated. The characteristic features of water-mediated interactions between hydrophobic solutes are found to be pressure-dependent. In particular, with increasing pressure we find that 1 the solvent-sepd.

Together, these observations lend strong support to the picture of the pressure denaturation process proposed previously by Hummer et al. The pressure dependence of the PMF between larger hydrophobic solutes shows that pressure effects on the interaction between hydrophobic amino acids may be considerably amplified compared to those on the methane-methane PMF.

We use long mol. In agreement with previous simulation studies, we find that the contact min. Both the entropy and enthalpy at the contact min. In contrast, we find that the solvent-sepd. The desolvation barrier is dominated by unfavorable enthalpy of maintaining a dry vol. However, the increasing height of the desolvation barrier with increasing pressures results from entropy changes at the barrier configurations.

Further resoln. A connection of these thermodn. For all investigated models and state points we calc. All water models exhibit too small hydration entropies, but show a clear hierarchy.

TIP3P shows poorest agreement with expt. As a first approxn. A rescaling procedure inspired by the information theory model of Hummer et al. In addn. In the second part of the paper we calc. We find that the temp. Nevertheless, differences between the models seem to require a more detailed mol. The TIP5P model shows by far the strongest temp.

The suggested d. The predicted assocn. Comparing different water models and exptl. A water model exhibiting a d. Berendsen et al. Mahoney and W. Jorgensen, J. Phys , ] water models using a temp. The solvation enthalpy and excess heat capacity is obtained from the temp. All three methods provide consistent results.

This observation is attributed to the enlarged heat capacity of the water mols. A detailed spatial anal. Differences between the two models with respect to the heat capacity in the xenon-xenon contact state are attributed to the different water model bulk heat capacities, and to the different spatial extension of the structure effect introduced by the hydrophobic particles.

Similarities between the different states of water in the joint xenon-xenon hydration shell and the properties of stretched water are discussed. Hydration effects on a pair of methane mols. The vol. The corresponding excess isothermal and adiabatic compressibilities were estd.

The dependence of excess vol. The maxima of excess vol. These features may be understood by the development, near the db, of a void vol. Connolly surface defined using a water-sized probe. These db properties for 2 methanes were consistent with well-corroborated exptl. At high pressures, the vols. This trend provided a rationalization for the compactness of pressure-denatured states of proteins. Taking the packing densities of pure nonpolar phases into consideration, the simulation results suggested that whether the activation vol.

Water hydrogen degrees of freedom and the hydrophobic effect. Hydrogen bonds are the key interaction that establishes the liq. Nevertheless, it is possible to construct an accurate mol. Using this model, we calc. The addn. The entropy of hydration from the model is about half the exptl. For the hydrophobic assocn. With the aid of literature exptl. Thus, the large and pos. Our key finding is that all of these phenomena are driven by the thermal pressure coeff. Remarkably, the soly. A review.

This review focuses on the striking recent progress in solving for hydrophobic interactions between small inert mols.

We discuss several new understandings. First, the inverse temp. The salting-out effects increase with protein and salt concentration. Dynamic binding capacity DBC is dependent on the binding constant, as well as on the flow characteristics during sample loading.

However, upon the addition of anti-chaotrophic salts such as ammonium sulfate and sodium sulfate in the solution, some of the water molecules will interact with the salt ions instead of the charged part of the protein.

When the protein-protein interactions in the solution become stronger than the solvent-solute interactions, the protein molecules react freely with one another - allowing them to aggregate and eventually precipitate out of the solution. Hence, the addition of salt in the solution reduces the solubility of different proteins to varying extents.

This theory states that the interaction between hydrophobic molecules is an entropy-driven process, based on the second law of Thermodynamics. The hydrophobic interaction between two or more non-polar molecules in a polar solvent solution is a spontaneous process governed by a change in entropy.

However, such interactions can be altered by controlling the temperature or by modifying the solvent polarity. As such, when a non-polar molecule comes into contact with a polar solvent such as water, there will be an increase in the degree of order of the solvent molecules surrounding the hydrophobic molecule.

As long as enthalpy does not increase significantly, this will produce a decrease in entropy and provide an overall positive change in the Gibbs energy. As such, the dissolution of a non-polar molecule in a polar solvent will not occur spontaneously since it is not thermodynamically favorable.

However, when you put two or more non-polar molecules in a polar environment, the hydrophobic surfaces of the macromolecules will be hidden from the polar surrounding and the hydrophobic molecules will aggregate spontaneously. The highly structured solvent molecules surrounding the exposed surface of the hydrophobic molecules will be displaced towards the bulk of the solvent consisting of less structured molecules.

Salt concentration The addition of structured salts to the equilibration buffer and sample promotes ligand-protein interactions in HIC Porath et al. As the salt concentration increases, the amount of bound protein increases as does the risk of protein precipitation at the higher ionic strength.

The figure below represents the Hofmeister series on the effect of some anions and cations on protein precipitation. Though sodium, potassium or ammonium sulphates produce relatively higher precipitation effects, these salts effectively promote ligand-protein interactions in HIC.

Most bound proteins are eluted by washing with water or dilute buffer at near neutral pH. In general, the strength of the interaction between proteins and the media decreases with increasing pH as a result of increased charge of the protein due to the titration of acidic groups. This effect can vary from protein to protein. Thus, pH can impact the level of protein binding and the selectivity of the media.

However, changes in pH do not have a significant effect over moderate ranges. Though it is useful to determine the optimal pH, pH gradients are not generally used as an elution method. Temperature The affinity of hydrophobic interactions increases with temperature. Temperature also impacts protein structure, solubility, and the interaction with the HIC matrix. Because temperature effects can be difficult to predict, it is generally not used to modulate separation using HIC.

Not surprisingly, experiments conducted at room temperature may not be reproduced in a cold room. Non-ionic adsorption chromatography of proteins. J Chromatogr , 57— PMID: Jennissen HP Multivalent interaction chromatography as exemplified by the adsorption and desorption of skeletal muscle enzymes on hydrophobic alkyl-agaroses.

J Chromatogr , 71—