B. Montgomery Pettitt

Proteins : a theoretical perspective of dynamics, structure, and thermodynamics

Potential Functions. Dynamical Simulation Methods. Thermodynamic Methods. Atom and Sidechain Motions. Rigid-Body Motions. Larger-Scale Motions. Solvent Influence on Protein Dynamics. Thermodynamic Aspects. Experimental Comparisons and Analysis. Concluding Discussion. References. Index.

Alkali halides in water: Ion–solvent correlations and ion–ion potentials of mean force at infinite dilution

Using the specialization of the extended RISM equation to infinitely dilute systems, we have calculated correlation functions and interionic potentials of mean force for a set of models corresponding to the first few alkali halides in water. From the results obtained at infinite dilution we calculate the lowest order corrections to the solution properties of the ions. Higher concentrations are explored by using the interionic potentials of mean force at infinite dilution as effective solvent mediated pair potentials. Our results indicate that certain thermodynamic properties, such as the mean activity coefficients and osmotic pressures, are quite sensitive to the details of both the theory and the potential models.

Structural and energetic effects of truncating long ranged interactions in ionic and polar fluids

The effects of Coulomb potential truncation schemes used in computer simulations of ionic and polar fluids are examined by use of integral equation techniques. A renormalized HNC type equation capable of describing both ionic and polar molecular fluids with truncated interactions is derived and applied to several model systems of interest. Good agreement is found between the integral equation results and Monte Carlo simulations of the same potential for dilute solutions of ions in a dielectric continuum. Very large effects on the distribution functions result from truncation of the electrostatic interaction in dilute systems. Even in comparatively dense systems, unrealistic pair correlations near the cutoff distance result from some of the proposed truncation schemes. The effect of Coulomb potential truncation for a molecular model of pure water is also studied. Significant errors appear in the second neighbor region for commonly used truncation schemes; a simple switching function that zeros the potential and its first derivative yields results closest to the Coulomb potential without truncation.

Application of an extended RISM equation to dipolar and quadrupolar fluids

A generalization of the RISM integral equation for site–site pair correlation functions previously proposed by us is discussed and applied to model liquids composed of strongly polar diatomic molecules. The nonuniform molecular charge distribution is represented by the introduction of charged interaction sites. The generalization consists of applying closure conditions analogous to those which are known to be reasonable for the description of atomic ionic fluids, and the corresponding renormalization of the contributions arising from long range forces. We discuss both the symmetry properties of the pair correlation functions in special cases and the dielectric properties implied by theory. Applications are presented for three two‐site models which differ substantially in the degree of asymmetry of the non‐Coulombic potential between the two sites, and for three three‐site models for Br2. The two sites models are compared to computer simulation results, and those for Br2 to experimental results. The analys...

Integral equation predictions of liquid state structure for waterlike intermolecular potentials

An application of our recently developed extended RISM equation formulation to several three‐site models of water is presented. The site–site correlation functions are obtained and compared to available computer simulation results. Further, the variation of liquid state structure with the model site charge is examined. The analysis of these results has demonstrated that the integral equation approach provides a correct qualitative description of the liquid structure, although the amplitudes of most structural features are somewhat less accurate that their positions. Comparison to our earlier results for simpler models suggests that the nature of the quantitative deficiencies of the approach is predictable. The charging study has shown that the development of waterlike structure with increasing site charge follows a qualitatively different pattern for oxygen–oxygen pairs, compared to those involving hydrogen. This is attributed to interference between the amplitudes characteristic of liquid water and of si...

The interionic potential of mean force in a molecular polar solvent from an extended RISM equation

The generalization of a recently proposed extension of the RISM integral equation to infinitely dilute isolated ions and ion pairs in polar, interaction site model, molecular solvents is outlined. An essential element of the development is the explicit separation of the contributions which yield a continuum dielectric solvent model from the remainder. Thus, it is only for this correction that one relies on the integral equation. Application is made to a system consisting of a diatomic polar solvent and atomic ions of varied charge and radius. The results of these calculations show that the present approach produces sensible qualitative features of ionic solvation including an appropriately varying degree of solvent orientational saturation with ionic charge and radius. Correspondingly, the calculated interionic potentials of mean force reproduce the same basic features manifest in already available studies of dipolar hard sphere solvents, including the positions of oscillatory features in the structure an...

A site-site theory for finite concentration saline solutions

A liquid state theory based on site–site integral equations is constructed to have the asymptotics given by angular expansion theory. This results in a theory which shows dielectric consistency, e.g., the dielectric constant as viewed from the solvent is the same as that viewed by the ions. Such consistency is lacking in other extended reference interaction site model (XRISM)‐based theories and leads to unrealistic structural predictions. The Kirkwood–Buff route to thermodynamics is used and allows a physical partitioning of the terms responsible for the solvation process. Sample results for a 1–1 salt are given.

Residence times of water molecules in the hydration sites of myoglobin

Hydration sites are high-density regions in the three-dimensional time-averaged solvent structure in molecular dynamics simulations and diffraction experiments. In a simulation of sperm whale myoglobin, we found 294 such high-density regions. Their positions appear to agree reasonably well with the distributions of waters of hydration found in 38 x-ray and 1 neutron high-resolution structures of this protein. The hydration sites are characterized by an average occupancy and a combination of residence time parameters designed to approximate a distribution of residence times. It appears that although the occupancy and residence times of the majority of sites are rather bulk-like, the residence time distribution is shifted toward the longer components, relative to bulk. The sites with particularly long residence times are located only in the cavities and clefts of the protein. This indicates that other factors, such as hydrogen bonds and hydrophobicity of underlying protein residues, play a lesser role in determining the residence times of the longest-lived sites.

A dielectrically consistent interaction site theory for solvent—electrolyte mixtures

Abstract A reformulation of reference interaction site model theory is proposed. The approach makes use of the formally correct asymptotic form of the correlations obtained from the one-center angular expansion technique. A modified closure, or equivalently, a modified propagation equation for site—site correlations is shown to incorporate the necessary information to allow dielectric consistency in finite-concentration salt solutions. Examples of the correlations and thermodynamics are given.

Sodium and chlorine ions as part of the DNA solvation shell.

The distribution of sodium and chlorine ions around DNA is presented from two molecular dynamics simulations of the DNA fragment d(C(5)T(5)). (A(5)G(5)) in explicit solvent with 0.8 M additional NaCl salt. One simulation was carried out for 10 ns with the CHARMM force field that keeps the DNA structure close to A-DNA, the other for 12 ns with the AMBER force field that preferentially stabilizes B-DNA conformations (, Biophys. J. 75:134-149). From radial distributions of sodium and chlorine ions a primary ion shell is defined. The ion counts and residence times of ions within this shell are compared between conformations and with experiment. Ordered sodium ion sites were found in minor and major grooves around both A and B-DNA conformations. Changes in the surrounding hydration structure are analyzed and implications for the stabilization of A-DNA and B-DNA conformations are discussed.