Lithium-ion solvation and diffusion properties in ethylene carbonate (EC) and propylene carbonate (PC) were studied by molecular simulation, experiments, and electronic structure calculations. Studies carried out in water provide a reference for interpretation. Classical molecular dynamics simulation results are compared to ab initio molecular dynamics to assess nonpolarizable force field parameters for solvation structure of the carbonate solvents. Quasi-chemical theory (QCT) was adapted to take advantage of fourfold occupancy of the near-neighbor solvation structure observed in simulations and used to calculate solvation free energies. The computed free energy for transfer of Li to PC from water, based on electronic structure calculations with cluster-QCT, agrees with the experimental value. The simulation-based direct-QCT results with scaled partial charges agree with the electronic structure-based QCT values. The computed Li/PF transference numbers of 0.35/0.65 (EC) and 0.31/0.69 (PC) agree well with NMR experimental values of 0.31/0.69 (EC) and 0.34/0.66 (PC) and similar values obtained here with impedance spectroscopy. These combined results demonstrate that solvent partial charges can be scaled in systems dominated by strong electrostatic interactions to achieve trends in ion solvation and transport properties that are comparable to ab initio and experimental results. Thus, the results support the use of scaled partial charges in simple, nonpolarizable force fields in future studies of these electrolyte solutions.

Ions transiting biomembranes might pass readily from water through ion-specific membrane proteins if those protein channels provide environments similar to the aqueous solution hydration environment. Indeed, bulk aqueous solution is an important reference condition for the ion permeation process. Assessment of this hydration mimicry view depends on understanding the hydration structure and free energies of metal ions in water to provide a comparison for the membrane channel environment. To refine these considerations, we review local hydration structures of ions in bulk water, and the molecular quasi-chemical theory that provides hydration free energies. In that process, we note some current views of ion-binding to membrane channels, and suggest new physical chemical calculations and experiments that might further clarify the hydration mimicry view.

The osmotic second virial coefficients, B 2 , for atomic-sized hard spheres in water are attractive (B 2 < 0) and become more attractive with increasing temperature (ΔB 2 /ΔT < 0) in the temperature range 300 K ≤ T ≤ 360 K. Thus, these hydrophobic interactions are attractive and endothermic at moderate temperatures. Hydrophobic interactions between atomic-sized hard spheres in water are more attractive than predicted by the available statistical mechanical theory. These results constitute an initial step toward detailed molecular theory of additional intermolecular interaction features, specifically, attractive interactions associated with hydrophobic solutes.protein folding | self-assembly | Pratt-Chandler theory S olvent-mediated, noncovalent interactions within biomolecular structures are decisive for their stability and functionality over an extended range of conditions (1). Hydrophobic interactions-a principal category of noncovalent interactions in water-exhibit strong and characteristic temperature dependences (2). Molecular-scale theories of hydrophobic interactions are judged by their ability to capture those temperature dependences. Defensible theories might eventually illuminate a valid explanation and might find broader utility in modeling biomolecular structure and function.The osmotic second virial coefficienthas so far been the only direct experimental check on the molecular theory of hydrophobic interactions between slightly soluble gases (A) in liquid water (3-6). Here g AA (r) is the usual radial distribution function of AA pairs at infinite dilution. Because of low solubilities for solutes of interest, the necessary experiments are challenging. The initial comparisons between the only available molecular-scale theory, the Pratt-Chandler (PC) theory (7), and direct measurements of B 2 showed poor agreement (3-5, 8).Explanations for the discrepancy have been suggested (9-11), but the underlying disagreement has persisted (12). One explanation for this discrepancy focused on the differences between the actual interactions for accessible experimental cases and the hard-sphere solute-water interactions natural for the molecular theory. In this setting, direct high-resolution determination of hydrophobic interactions for the hard-sphere models treated by the theory would be a helpful step, but that has not been accomplished so far. The case of atomic-sized hardsphere solutes has not been treated specifically, mostly because hard-sphere models are inconvenient in available molecular dynamics simulations.These problems are of basic importance because hydrophobic interactions are acknowledged as the dominant factor that drives protein folding (13,14). Hydrophobic interactions are also expected to become more favorable with increasing temperature for physiological temperatures. Hydrophobic interactions can then be described as favorable for aggregation and endothermic at moderate temperatures. This is a primary conceptual puzzle that theories of hydrophobic effects should clarify.Summaries of the substa...

We report atomically detailed molecular dynamics simulations of the permeation of the lethal factor (LF) N-terminal segment through the anthrax channel. The N-terminal chain is unstructured and leads the permeation process for the LF protein. The simulations are conducted in explicit solvent with Milestoning theory, making it possible to extract kinetic information from nanoseconds to milliseconds time scales. We illustrate that the initial event is strongly influenced by the protonation states of the permeating amino acids. While the N-terminal segment passes easily at high protonation state through the anthrax channel (and the ϕ clamp), the initial permeation represents a critical step, which can be irreversible and establishes a hook in the channel mouth.

Anion hydration is complicated by H-bond donation between neighboring water molecules in addition to H-bond donation to the anion. This situation can lead to competing structures for chemically simple clusters like (H 2 O) n Cl − and to anharmonic vibrational motions. Quasi-chemical theory builds from electronic structure treatment of isolated ion-water clusters, partitions the hydration free energy into inner-shell and outer-shell contributions, and provides a general statistical mechanical framework to study complications of anion hydration. The present study exploits dynamics calculations on isolated (H 2 O) n Cl − clusters to account for anharmonicity, utilizing ADMP (atom-centered basis sets and density-matrix propagation) tools. Comparing singly hydrated F − and Cl − clusters, classic OH-bond donation to the anion occurs for F − , while Cl − clusters exhibit more flexible but dipole-dominated interactions between ligand and ion. The predicted Cl − -F − hydration free energy difference agrees well with experiment, a significant theoretical step for addressing issues like Hofmeister ranking and selectivity in ion channels.