Using classical molecular dynamics simulations, we study ion-ion interactions in water. We study the potentials of mean force (PMF) for the full set of alkali halide ion pairs, and in each case, we test different parameter sets for modeling both the water and the ions. Altogether, we compared 300 different PMFs. We also calculate association equilibrium constants (K A ) and compare them to two types of experiments. Of additional interest here was the proposition of Collins called the 'law of matching water affinities', where the relative affinity of ions in solution depends on the matching of cation and anion sizes. From observations on the relative depths of the free energies of the contact ion pair (CIP) and the solvent-shared ion pair (SIP), along with related solvent structure analyses, we find a good correlation with this proposition: small-small and large-large should associate in water and small-large should be more dissociated.

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Water plays a central role in the structures and properties of biomolecules--proteins, nucleic acids, and membranes--and in their interactions with ligands and drugs. Over the past half century, our understanding of water has been advanced significantly owing to theoretical and computational modeling. However, like the blind men and the elephant, different models describe different aspects of water's behavior. The trend in water modeling has been toward finer-scale properties and increasing structural detail, at increasing computational expense. Recently, our labs and others have moved in the opposite direction, toward simpler physical models, focusing on more global properties-water's thermodynamics, phase diagram, and solvation properties, for example-and toward less computational expense. Simplified models can guide a better understanding of water in ways that complement what we learn from more complex models. One ultimate goal is more tractable models for computer simulations of biomolecules. This review gives a perspective from simple models on how the physical properties of water-as a pure liquid and as a solvent-derive from the geometric and hydrogen bonding properties of water.

Polyelectrolytes are electrolytes asymmetric both in charge and size. Their properties in solution are dominated by Coulombic forces, and without a detailed understanding of these interactions, no interpretation of experimental data is possible. This paper is a review of recent developments in the theory of highly asymmetric electrolytes of spherical shape resembling surfactant micelles. Three different models are discussed: (a) the cell model, which is focused on the small ion-macroion interaction; (b) the model that treats the solution as an effective one-component fluid of macroions; and (c) the isotropic model, where the solution is represented as a mixture of charged spheres. Traditionally, the electrostatic interactions are accounted for via the solution of the Poisson-Boltzmann equation. This theory, however, ignores the fluctuations around the most probable distribution and may yield poor results for systems with multivalent ions. This paper focuses on developments beyond the Poisson-Boltzmann theory; the results of computer simulations and integral equation theories represent the major part of the review.

For biotechnological drugs, it is desirable to formulate antibody solutions with low viscosities. We go beyond previous colloid theories in treating protein–protein self–association of molecules that are antibody–shaped and flexible and have spatially specific binding sites. We consider interactions either through fragment antigen (Fab–Fab) or fragment crystalizable (Fab–Fc) binding. Wertheim's theory is adapted to compute the cluster–size distributions, viscosities, second virial coefficients, and Huggins coefficients, as functions of antibody concentration. We find that the aggregation properties of concentrated solutions can be anticipated from simpler–to–measure dilute solutions. A principal finding is that aggregation is controllable, in principle, through modifying the antibody itself, and not just the solution it is dissolved in. In particular: (i) monospecific antibodies having two identical Fab arms can form linear chains with intermediate viscosities. (ii) Bispecific antibodies having different Fab arms can, in some cases, only dimerize, having low viscosities. (iii) Arm–to–Fc binding allows for three binding partners, leading to networks and high viscosities.