B. M. Pettitt's Publications

SCF-LCAO-MO calcns. were made for NeHHe+. The complex has a min. energy of -131.49544 hartree, corresponding to He-H and Ne-H bond distances of 1.875 and 2.05 bohr, resp. The reactions NeH+ + He -> NeHHe+ and Ne + HHe+ -> NeHHe+ are exothermic by 9.4 and 14.5 kcal/mol, resp. [on SciFinder (R)]

Keywords: Heat of reaction (of helium-group gas hydride ion); Potential energy and function (surface of, for helium hydride ion collinear reaction with neon) MO hydride neon helium; potential surface hydride helium neon; heat reaction helium neon hydride; energy potential helium neon hydride

The total Compton profiles and anisotropies assocd. with momentum distribution along vectors parallel and perpendicular to bond axes in alkali chloride mols. are calcd. and related to changes in charge distributions accompanying bond formation. [on SciFinder (R)]

Keywords: Alkali metal chlorides Role: PRP (Properties) (Compton profile anisotropy of, MO calcn. of); Bond formation (alkali metal-chlorine, Compton profile anisotropy in relation to); Molecular orbital (ab initio SCF, Compton profile anisotropy of alkali metal chlorides); Compton effect (profiles, of alkali chlorides, charge distribution in relation to, MO calcn. of) alkali chloride Compton profile anisotropy

Anisotropies assocd. with momentum distributions along vectors parallel and perpendicular to bond axes in alkali metal bromide mols. are computed and analyzed. An attempt is made to relate these to charge cloud deformations accompanying mol. formation. The parallel profile assocd. with the valence p orbital is the dominating factor detg. the relative shapes of the total profile anisotropies in the low momenta regions Pz ? 0.5. [on SciFinder (R)]

Keywords: Alkali metal bromides Role: PRP (Properties) (Compton profile anisotropy in); Compton effect (profiles, anisotropy of, in alkali metal bromide) Compton profile lithium sodium bromide

An empirical relation between zero point Compton profile anisotropies DJ(0) and nuclear charges is noted. To a good approxn., DJ(0) = Nln(Zb/Za) for alkali halide mols., AB. [on SciFinder (R)]

Keywords: Molecules (Compton profile anisotropies in); Alkali metal halides Role: PRP (Properties) (Compton profile anisotropies in); Nuclear charge (Compton profile anisotropies in relation to); Compton effect (in mols. and in solids, anisotropies of) Compton profile mol solid; nuclear charge Compton profile; alkali halide Compton profile

Calcns. of Compton profiles and parallel-perpendicular anisotropies in alkali fluorides are presented and analyzed in terms of mol. charge distributions and wave function character. The parallel profile assocd. with the valence p orbital is the principal factor detg. the relative shapes of the total profile anisotropies in the low momentum region. [on SciFinder (R)]

Keywords: Electron configuration; Wave function (Compton profile anisotropies in alkali metal fluorides in relation to); Alkali metal fluorides Role: PRP (Properties) (Compton profile anisotropies in, electron configuration in relation to); Compton effect (anisotropies of, in alkali metal fluorides, electron configuration in relation to); Electron configuration (p-, Compton profile anisotropies in alkali metal fluorides in relation to) Compton profile alkali metal fluoride

SCF-LCAO calcns. were done to obtain: (a) the optimized DIM potential-energy (PE) surface for the reaction of ArH+ and He; (b) the parameters of the Morse PE curves of ArH+, ArH, HeH+, HeH, HeAr+, and HeAr; and (c) the frequencies of the sym. and asym. stretching vibrations of 40ArHHe+, 40ArDHe+ 36ArHHe+, and 36ArDHe+. For (ArHHe)+ at the PE min., the energy is -529.7778 hartree, and the Ar-H and H-He interat. distances are 2.51 and 2.82 bohr, resp. The energies for the exothermic reactions ArH+ + He -> ArHHe+, Ar + HHe+ -> ArHHe+, and Ar + HeH+ -> ArH+ + He are 1.58, 41.4, and 39.8 kcal/mol, resp. [on SciFinder (R)]

Keywords: Heat of reaction (of argon and hydrohelium(1+), SCF-LCAO calcns. of); Molecular vibration (of argon-helium-hydrogen and argon-deuterium-helium triat. monopos. ions, SCF-LCAO calcns. of); Potential energy and function (Morse, for diat. mols. and monopos. ions from argon and helium and hydrogen, SCF-LCAO calcns. of); Potential energy and function (surface, for helium-hydroargon(1+) reaction, SCF-LCAO calcns. of) potential surface helium hydroargon cation; reaction helium hydroargon cation SCF; heat reaction argon hydrohelium cation; vibration triatomic argon helium hydrogen; Morse potential argon helium hydrogen; hydride argon helium Morse potential; deuterium argon helium triatomic vibration; hydrogen argon helium triatomic vibration

A correlation between bond polarities and zero point Compton profile anisotropies is shown for alkali halide mols. The correlation derives from the fact that both quantities are detd. by mol. binding and antibonding forces and are thus functionally related to nuclear charge ratios. [on SciFinder (R)]

Keywords: Compton effect (bond polarity in alk. metal halide in relation to); Alkali metal halides Role: PRP (Properties) (polarity and Compton profile anisotropy in); Bond (polarity of, in alk. metal halides, Compton profile anisotropy in relation to) Compton effect bond polarity halide; alkali halide Compton bond polarity

A classical derivation of a dipole moment model derived earlier (M. and K. 1976, 77) by a quantum mech. implicit perturbation technique is given. This model is used to det. the bond polarities of the posttransition (Groups IIIA-VIIA) hydrides. The polarity measures the extent of charge transfer in a bond. Polarities of alkali halides and posttransition hydrides are used to illustrate the gradual change in bond polarities with nuclear charge across the periodic table. [on SciFinder (R)]

Keywords: Nuclear charge (bond polarity in hydrides in relation to); Alkali metal halides; Hydrogen halides Role: PRP (Properties) (bond polarity of); Bond (polarity of, of posttransition metal hydrides); Electric charge (transfer of, in posttransition metal hydride bond, polarity in relation to); Group IIIA element compounds; Group IVA element compounds; Group VA element compounds; Group VIA element compounds Role: PRP (Properties) (hydrides, bond polarity of); Hydrides (posttransition, bond polarity of) bond polarity posttransition hydride; IIIA hydride bond polarity; IVA hydride bond polarity; VA hydride bond polarity; VIA hydride bond polarity; VIIA hydride bond polarity; hydrogen halide bond polarity; alkali halide bond polarity

A procedure, based on Rayleigh-Schroedinger perturbation theory, for obtaining vibrational, rotational, and temp.-dependent Compton profiles and profile anisotropies is presented and applied to H2 to test its validity. The computer vibrational-rotational dependence agrees well with the results of V. H. Smith et al. (1977) who obtained vibrational-rotational profiles for H2 by numerically integrating the Schroedinger equation for nuclear motion. The procedure is used to obtain vibrational, rotational, and temp.-dependent profiles and anisotropies for some alkali halide mols. The vibrational and temp. dependence of the parallel-perpendicular anisotropies in these mols. is substantial. [on SciFinder (R)]

Keywords: Alkali metal halides Role: PRP (Properties) (Compton profile anisotropies in, rotational, temp., and vibrational dependence of); Molecular rotation; Molecular vibration (alkali metal halide Compton profile anisotropy dependence on); Compton effect (profiles, for alkali metal halides, anisotropies of) alkali halide Compton profile anisotropy

A generalization of the RISM (ref. interaction site model) integral equation for site-site pair correlation functions previously proposed by the authors is discussed and applied to model liqs. composed of strongly polar diat. mols. The nonuniform mol. 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 at. ionic fluids, and the corresponding renormalization of the contributions arising from long range forces. The symmetry properties of the pair correlation functions in special cases and the dielec. properties implied by theory are discussed. 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-site models for Br2. The two sites models are compared to computer simulation results, and those for Br2 to exptl. results. The integral equation is well balanced in that in every case the qual. features of the liqs. structure which are introduced by polarity are well represented, even in cases where the site-site potentials are individually much larger than kBT. In cases where the mol. shape and polar forces are in competition, the results are of comparable accuracy to the corresponding theory for nonpolar systems. In the extreme case where changes in orientational structure can occur without interfering with packing requirements, the results appear quant. less reliable. [on SciFinder (R)]

Keywords: Dielectric property (of dipolar and quadrupolar fluids, ref. interaction site model in); Statistical mechanics (ref. interaction site model, of dipolar and quadrupolar fluids); Distribution function (pair correlation, site-site, of dipolar and quadrupolar fluids) statistical mechanics quadrupolar fluid; correlation function quadrupolar fluid; dielec property quadrupolar fluid

An application of the authors recently developed extended RISM equation formulation (1981) to several 3-site models of H2O is presented. The site-site correlation functions are obtained and compared to available computer simulation results. Further, the variation of liq. state structure with the model site charge is examd. The anal. of these results has demonstrated that the integral equation approach provides a correct qual. description of the liq. structure, although the amplitudes of most structural features are somewhat less accurate than their positions. Comparison to earlier results for simpler models suggests that the nature of the quant. deficiencies of the approach is predictable. The charging study has shown that the development of waterlike structure with increasing site charge follows a qual. different pattern for O-O pairs, compared to those involving hydrogen. This is attributed to interference between the amplitudes characteristic of liq. water and of simple liqs. This is the origin of a relatively flat 0-0 correlation function for several models studied in the past, and, further, that such results should not be properly characterized as ünstructured. [on SciFinder (R)]

Keywords: Liquid structure (waterlike intermol. potentials in); Potential energy and function (intermol., liq. structure in relation to) liq structure potential; water liq structure

The generalization of a recently proposed extension of the RISM (ref. interaction site model) integral equation to infinitely dil. isolated ions and ion pairs in polar interaction site model mol. solvents is outlined. An essential element of the development is the explicit sepn. of the contributions which yield a continuum dielec. 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 diat. polar solvent and at. ions of varied charge and radius. The results of the calcns. show that this approach produces qual. features of ionic solvation including an appropriately varying degree of solvent orientational satn. with ionic charge and radius. Correspondingly, the calcd. 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 and the relatively short spatial range of the corrections to the continuum dielec. theory. [on SciFinder (R)]

Keywords: Solutes (in polar solvents, interionic potential in relation to); Liquid structure (interionic potential of mean force in mol. polar solvent in relation to); Ion pairs; Ions in liquids (interionic potential of, in mol. polar solvent); Solvation (ionic, interionic potential of mean force in mol. polar solvents in relation to); Electric charge (of ions in polar solvents, interionic potential of mean force in relation to); Dielectric constant and dispersion (of polar solvent, interionic potential of mean force in relation to); Potential energy and function (interionic, of mean force in mol. polar solvent from extended from IRSM equation); Solvents (polar, mol., interionic potential of mean force in) interionic potential mean force solvent; RISM polar solvent interionic potential

The structure of liq. MeOH was studied using the recently proposed extended RISM integral equation and Jorgensen's transferable intermol. potentials (TIPS). Results are obtained as a function of mol. polarity by scaling the partial Coulombic charges located at mol. interaction sites. At the exptl. d., packing forces are predominant in detg. many features of the liq. structure, as reflected in site-site correlation functions. The influence of H bonding is best characterized as a narrowing in the mol. distributions, resulting from an accommodation of the attractive forces within structural alternatives consistent with packing constraints. [on SciFinder (R)]

Keywords: Hydrogen bond (in liq. methanol, structure in relation to); Liquid structure (of methanol, hydrogen bonding in relation to); Distribution function (radial, site-site, in liq. methanol) methanol liq hydrogen bond structure

The parallel-perpendicular Compton-profile anisotropies were calcd. for the 1st-row diat. hydrides. Both the total and MO anisotropies present trends that were related to the nature of the chem. binding in the mols. [on SciFinder (R)]

Keywords: Bond (in diat. hydrides of 1st row, Compton profiles in relation to); Compton effect (profiles, of diat. hydrides of 1st row, bonding in relation to); Hydrides Role: PRP (Properties) (diat., Compton profiles of 1st-row, bonding in relation to) beryllium hydride Compton profile bonding; lithium hydride Compton profile bonding; diatomic hydride Compton profile bonding; hydrogen fluoride Compton profile bonding; imidogen Compton profile bonding; methylidyne Compton profile bonding; hydroxyl Compton profile bonding; borane Compton profile bonding

A simple modification of the HNC-like closure within the extended RISM equation formalism is considered which ensures that the asymptotic form of the site-site direct correlation functions is consistent with the dielec. const. The short ranged structural results obtained with the modification are compared with those following from the original closure for 3 strongly polar diat. models, and show very small differences. These results demonstrate both that the short ranged results are only weakly coupled to the asymptotic amplitudes, and that the latter can potentially be cor. in a relatively straighforward manner. [on SciFinder (R)]

Keywords: Dielectric constant and dispersion (of mol. liqs., extended interaction site models for correlation functions in relation to); Distribution function (correlation, of mol. liqs., extended interaction site models for, dielec. const. in relation to) interaction site model liq correlation; dielec const liq correlation function

The contribution of electrostatic interactions to a range of structural, energetic, and dynamic properties of the alanine dipeptide is examd. An empirical energy function is employed to represent the dipeptide, and the partial at. charges are varied from zero to values used in std. models for amino acids and proteins. Although there are large differences in the abs. energy of models with different charges, the relative energies of the various dipeptide conformers are less sensitive to the charges. The min. energy structures of the conformers are only weakly dependent on the charges. A normal model anal. shows that only a few modes are sensitive to the charges and that thermodn. quantities, which represent sums over the modes, are essentially the same for all the models. Comparison of the harmonic dynamics results with those from an ensemble of mol. dynamics trajectories reveals that the electrostatic contributions to the potential surface introduce significant anharmonic effects. [on SciFinder (R)]

Keywords: Enthalpy and Enthalpy function; Entropy; Free energy (harmonic, of alanine dipeptide); Hydrogen bond (in alanine dipeptide, electrostatic contribution in relation to); Heat capacity; Molecular dynamics; Molecular vibration (of alanine dipeptide); Molecular structure (of alanine dipeptide, electrostatic contribution in); Conformation and Conformers (of alanine dipeptide, electrostatic contribution in relation to); Potential energy and function; Potential energy surface and hypersurface (of alanine dipeptide, electrostatic contribution to); Peptides Role: PRP (Properties) (di-, alanine-contg., electrostatic interaction in, calcn. of) alanine dipeptide electrostatic interaction; methylalanylacetamide electrostatic interaction; structure alanine dipeptide electrostatic interaction; mol dynamics alanine dipeptide; energy alanine dipeptide electrostatic interaction; thermodn alanine dipeptide electrostatic interaction; conformation alanine dipeptide electrostatic interaction

An exact form for the time dependent resonance Raman kernel at finite temperature is derived under the assumption that the ground and excited state potential surfaces of the system are harmonic. The resultant expression can be evaluated by matrix algebra and Fourier transformed numerically to recover Raman scattering and excitation profiles.

Keywords: Raman Spectroscopy; Line Shape; Resonance Scattering; Temperature Dependence

Theoretical results obtained with the extended reference interaction site (XRISM) formalism are presented for site–site solute solvent correlations and solute–solute potentials of mean force for infinitely dilute polar molecular solutes in various polar solvents. The standard RISM site–site Ornstein–Zernike like equations, in a Coulomb renormalized form, with a hypernetted chain (HNC) analog closure are used to derive results for polar molecular solutes in polar molecular solvents. For a dipolar diatomic solute the difference in the solvation behavior between atomic and molecular solvents is examined. Finite concentration results are compared with the infinite dilution intermolecular site–site potentials of mean force for diatomic molecules in a simple fluid solvent.

Keywords: Polyatomic Molecules; Solutions; Correlations; Intermolecular Forces; Liquid Structure

The results of an application of integral equation theory to the detn. of the intramol. potential of mean force for the alanine dipeptide, N-methylalanine acetamide, in aq. soln. are presented. The calcns. are based on Ornstein-Zernike-like equations for polar systems with an intramol. superposition approxn. The solvated free energy surface for the dipeptide as a function of the dihedral angles f and y (Ramachandran plot) is detd. and compared with the vacuum surface calcns. Conformations that are essentially forbidden in vacuum are found to be significant in aq. soln. The solvent contributions to the free energy surface are decompd. into enthalpic and entropic terms. Possible applications and extensions of the method are outlined. [on SciFinder (R)]

Keywords: Conformation and Conformers (of methylalanine acetamide, potential energy surface calcns. in relation to); Potential energy surface and hypersurface (conformational, of methylalanine acetamide) methylalanine acetamide potential energy surface conformation; alanine dipeptide potential energy surface conformation

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.

Keywords: Computerized Simulation; Potentials; Liquids; Coulomb Field; Intermolecular Forces

By using the specialization of the extended RISM equation to infinitely dil. systems, correlation functions and interionic potentials of mean force were calcd. for a set of models corresponding to the first few alkali halides in water. From the results obtained at infinite diln., the lowest order corrections were calcd. to the soln. properties of the ions. Higher concns. are explored by using the interionic potentials. The results indicate that certain thermodn. properties, such as the mean activity coeffs. and osmotic pressures, are quite sensitive to the details of both the theory and the potential models. [on SciFinder (R)]

Keywords: Alkali metal halides Role: PRP (Properties) (interionic potentials for, in aq. solns.); Activity; Osmotic pressure (ion-solvent correlations and ion-ion potentials of means force at infinite diln. in relation to); Distribution function (correlation, of alkali halides in water); Potential energy and function (interionic, of alkali halides in water) alkali halide aq ion solvent correlation; potential infinite diln alkali halide aq

A review with 80 refs. Energy of interaction between drugs and receptors is discussed in terms of drug design. [on SciFinder (R)]

Keywords: Receptors Role: BIOL (Biological study) (drug interaction energies with, drug design in relation to) review drug design interaction energy

A model is presented for detg. the intramol. potential of mean force for flexible polyat. mols. in aq. soln. This is an essential step in developing a reduced simulation technique for studying solvated biopolymers. The Ornstein-Zernike integral equation theory within a superposition formalism led to a convenient and efficient method for calcg. the solvent-modified intramol. potential. Solute-solvent distribution functions for the atoms (sites) composing the polyat. mol. are evaluated individually and introduced into the appropriate integral equations to obtain the site-site potentials of mean force for all distinct atom pairs in the mol. The superposition approxn. plus an empirical energy function for the internal degrees of freedom can then be employed to det. the total solvent-modified potential of mean force surface for the mol. system. An application to the evaluation of the intramol. potential of mean force surface for the alanine dipeptide (N-methylalanylacetamide) under vacuum and in aq. soln. is given to illustrate the method. [on SciFinder (R)]

Keywords: Statistical mechanics (Ornstein-Zernike-type integral equation, solvent-modified potential surface for flexible internal degrees of freedom of biomols. construction by); Solvation (of biomols., potential surface for); Potential energy surface and hypersurface (solvent-modified, for flexible internal degrees of freedom of bimols.); Biopolymers; Peptides Role: ANST (Analytical study) (solvent-modified, potential surface for) biomol solvation potential surface calcn; statistical mechanics potential surface peptide

Recently developed integral equation methods for the evaluation of intermol. and intramol. interactions in a polar solvent medium are discussed and representative applications are presented. Examples include solvent modification of interionic interactions between at. or mol. ions in water and liq. environment induced shifts in conformational equil. for both non-polar and polar flexible mols. in water. Emphasis is placed on the features of these phenomena which can be traced specifically to the molecularity of the solvent and hence cannot be adequately reproduced by a simple continuum dielec. solvent representation. 49 Refs. [on SciFinder (R)]

Keywords: Solvent effect (on mol. interactions); Potential energy and function (solvent effects on) review solvent mediated mol interaction

Calcns. of the site-site correlation functions for a model of water were performed as functions of d. or pressure at fixed temp. These calcns. are discussed and compared to neutron-scattering data. They structure of liq. water at high pressure is consistent with a substantially distorted H-bonding network. Unlike MeOH, water cannot easily accommodate structures assocd. with directional attractive forces in the region of several kilobars of pressure. [on SciFinder (R)]

Keywords: Hydrogen bond (in water at high pressure); Liquid structure (of high-d. water); Distribution function (correlation, of water, at high pressure) water structure correlation function; hydrogen bond water

Recently developed integral equation methods for the evaluation of correlations of polar mol. solutes in polar solvent media have been solved for the N-Me alanyl acetamide in H2O. The results are compared with simulations of similar model systems. The use of the full mol. site-site correlations detd. in this work can be used in approx. nonsuperposition theories for conformational populations in soln. [on SciFinder (R)]

Keywords: Hydration (of peptides, model for); Peptides Role: BIOL (Biological study) (structure of water around, calcn. of); Hydrogen bond (water structure surrounding peptides response to, modeling of) peptide water structure model; methylalanyl acetamide water structure model

An inhomogeneous anisotropic integral equation theory is used to predict the 6-fold pattern of intensity in the structure factor for graphite intercalation compds. The competition of length scales implied by particle size and the underlying lattice through the interplay of the liq. packing structure with the graphitic external field is shown to be responsible for the obsd. halo-like features in S(k). By using a d. functional motivated ansatz no explicit truncation of the angular Fourier components of the d. distributions was necessary. [on SciFinder (R)]

Keywords: Alkali metals Role: PRP (Properties) (structure factor of graphite intercalation compds. contg.); Potential energy and function (periodic, two-dimensional fluids in); Distribution function (structure factor, of graphite intercalation compds.) structure factor graphite intercalation compd

Preliminary results are reported for dynamic computer free energy simulations for a pair of Cl-, ions in H2O with a near-ion-contact starting configuration. A contact min. is obsd. in which the 2 ions are able to oscillate for some time. Water mols. form bridging H bonds which stabilize the ion pair. [on SciFinder (R)]

Keywords: Ion pairs (chloride-chloride, at contact, simulation of) ion pair chloride chloride solvated; computer simulation chloride ion pair; contact chloride chloride ion pair

An effective intramol. potential is presented for use in conjunction with existing 3-site models of water. Two commonly used internal geometries were fit to the same form and yield slightly different parameterizations. By including a Urey-Bradley-like term in an otherwise std. mol. mechanics form, the exptl. transition frequencies of water monomer can be reproduced accurately. Good qual. agreements for spectral shifts were subsequently found for the models in condensed-phase applications. Harmonic anal. of clusters indicates good qual. agreement with exptl. environmental shifts in frequencies at low temps. for these models. This model should be useful for a wide variety of applications including simulations of biopolymers and ionic solns. [on SciFinder (R)]

Keywords: Potential energy and function (intramol., for water) intramol model potential water

A quant. study is reported of the Cl-Cl- solvent-averaged potential in water, detd. by using the ümbrellasampling method and the Hamiltonian used in a recent integral equation study. The resulting potential of mean force is compared to the result from previous approx. integral equation studies. The results display a clear contact stabilization in contrast to the predictions of continuum theory. [on SciFinder (R)]

Keywords: Potential energy and function (pair, solvent-averaged, between two chloride ions in water, quantum statistical mech. study of); Statistical mechanics (quantum, of chloride ion pairs in water) chloride ion pair water; potential interionic chloride water

The extended ref. interaction site method is used to calc. the structure of water behind a shock front. The competing effects of increased d. and temp. modify the correlation functions in a manner that is qual. consistent with both expectation and recent exptl. results. [on SciFinder (R)]

Keywords: Shock wave (in structure of water); Liquid structure (water, behind shock waves) water structure shock wave effect

Mol. dynamics computer simulations utilizing the thermodn. cycle-perturbation method were used in preliminary calcns. of the relative free energies of binding for 2 new compds. (I and II) with antiviral activity to the coat proteins of human rhinovirus 14. The results suggest that intrinsic protein-ligand interactions dictate relative binding affinities, whereas relative desolvation energies contribute little to the net differences in the free energy of binding. These results and similar calcns. currently in progress should contribute to the design of new mols. with enhanced binding affinity for the rhinovirus coat proteins. [on SciFinder (R)]

Keywords: Free energy (of binding, of phenoxyisoxazole to rhinovirus coat protein, by perturbation method); Solvation (of phenoxyisoxazole antiviral agents); Molecular association (of phenoxyisoxazole antiviral drugs, with rhinovirus coat proteins, thermodn. of); Process simulation (mol. dynamics, of phenoxyisoxazole antiviral agents); Virus (rhino-, coat proteins, phenoxyisoxazole inhibitors binding to, thermodn. of); Molecular structure-biological activity relationship (virucidal, of phenoxyisoxazoles) antiviral phenoxyisoxazole mol dynamics; thermodn solvation binding phenoxyisoxazole antiviral; free energy phenoxyisoxazole

Integral equation theory is applied to the detn. of the intramol. potential of mean force for the glycine peptide, N-acetylglycyl-N-methylamide, in aq. soln. The solvated free energy for the dipeptide as a function of the dihedral angles F and Y (Ramachandran plot) is detd. and compared with the vacuum surface. Conformations forbidden in vacuum are found to be populated in aq. soln. The results for the glycine dipeptide are compared to a parallel study on the alanine dipeptide. Solvent effects are responsible for the extent of many of glycine's properties related to flexibility. [on SciFinder (R)]

Keywords: Conformation and Conformers; Potential energy surface and hypersurface (of glycine dipeptide); Solvent effect (on conformation of glycine dipeptide); Potential energy and function (conformational, of glycine dipeptide) glycine dipeptide conformation

A method that locates transition state structures homologous reactions and, with the use of the thermodn. cycle-perturbation technique, dets. the relative free energy of activation between the transition states is presented. A simple model system which displays the problem of finding condensed phase transition states is used to illustrate the method. [on SciFinder (R)]

Keywords: Free energy of activation (between transition state structures of homologous reactions, geometric method for calcn. of); Transition state structure (location of, between homologous reactions, geometric method for detn. of) transition state structure free energy activation

Simulations of the residual configurational entropy of a protein in the native state suggest that it is nearly an order of magnitude larger than the entropy of denaturation. The implications of this result are discussed. [on SciFinder (R)]

Keywords: Proteins Role: PRP (Properties) (configurational entropy of, simulation of); Entropy (of denaturation, of proteins, configurational entropy in relation to); Entropy (configurational, of proteins, simulation of) protein configurational entropy

Keywords: Proteins Role: PRP (Properties) (dynamics and structure and thermodn. of); Thermodynamics (of proteins, dynamics and structure in relation to) protein dynamics structure thermodn book

A review with 38 refs. By appropriate choice of the level of theor. treatment, the problem of accounting for the soln. environment in the modeling of biopolymer conformation and interactions is becoming accessible to direct computational evaluation. In this article, the authors summarize a no. of methods that have been recently applied in this context, emphasizing those other than direct all-atom computer simulation. [on SciFinder (R)]

Keywords: Biopolymers Role: ANST (Analytical study) (conformation and interactions of, solvation effects in, modeling of); Solvation (in biopolymer solns., modeling of, conformation and interactions in relation to); Conformation and Conformers (of biopolymers, solvation effects in, modeling of); Process simulation (of solvation effects in biopolymer soln.) review solvation effect biopolymer; conformation biopolymer solvation effect review; process simulation biopolymer solvation review

We have performed a molecular dynamics simulation of the enkephalin derivative Tyr-(D)Pen-Gly-Phe-(D)Pen (DPDPE) in aqueous solvent. Electrostatic interactions were calculated with the Ewald method so as to accurately model the large interactions between the DPDPE zwitterion and the solvent and to avoid the use of electrostatic cutoff's or neutral chemical blocking groups. DPDPE is found to be extremely constrained with very little variation in the main-chain dihedral angles. Flexibility found in the region of the central glycine is greatly restricted compared with glycines in straight-chain peptides. Several conformational transitions are observed for the two aromatic side chains, indicating a high degree of flexibility in the side chains and that DPDPE does not have a single conformation in solution. This suggests that the arrangement of the tyrosine and phenylalanine aromatic residues in the bound conformation may be selected by the receptor environment. The main-chair conformation of DPDPE in solution has a parallel arrangement of peptide groups. This electrostatically unfavorable structure is stabilized by interactions of the carbonyls with the solvent. Solvent structure around the N terminus is found to be considerably localized, involving short ammonium cation to water contacts with lifetimes of the order of 50 ps or more. In comparison, water structure around the C terminus is much more mobile with lifetimes of the order of 20 ps or less.

A computational demonstration of a form of constant-chemical-potential molecular dynamics shows the feasibility of the proposed method. The technique is based on using a Lagrangian for a system that includes extension variables to couple the number of particles with the chemical potential and auxiliary variable allowing for the insertion of new particles and the destruction of existing ones. Density dependence, equilibrium and non-equilibrium properties are considered.

A review, with 23 refs., on a representative 150-ps mol. dynamics simulation of metmyoglobin in water, the general methods used in this dynamic simulation, and spatial and temporal fluctuations. [on SciFinder (R)]

Keywords: Myoglobins Role: PRP (Properties) (time scales and fluctuations of metmyoglobin dynamics in aq. soln.) review metmyoglobin dynamics soln

The aqueous solvation thermodynamics of cis- and trans-N-methylacetamide is studied by integral equation theories and molecular dynamics simulations and compared with Monte Carlo results (Jorgensen, W. L.; Gao, J. J. Am. Chem. Soc. 1988, 110, 4212). Although the hypernetted chain (HNC) approximation is generally recommended for polar systems, the solvation free energy derived from the Gaussian fluctuation (GF) approximation gives much better absolute solvation thermodynamics. With the same atomic charges for the two conformers, the difference in solvation free energy between the cis and trans conformers equals 1-2 kcal/mol from the HNC and GF approximations, in approximate agreement with the value of 2.2 kcal/mol from a Monte Carlo simulation with very similar parameters. The simpler superposition approximation introduced by Pettitt and Karplus (Chem. Phys. Lett. 1985, 121, 194) gives results for the relative solvation thermodynamics (cis versus trans conformers) that compare well with the more exact integral equation theories.

We present two techniques for implementing a new method of simulating an entire virion. Earlier computer simulations of a capsid protein revealed large edge effects due to the use of free standing boundaries. Because of the size of a given protomer, conventional three-dimensional periodic boundary conditions would be extremely wasteful. This would require an extremely large number of solvent molecules, and therefore would be computationally feasible for only a fragment of the entire virion. The new method employs non-space-filling computational cells in molecular modeling and molecular dynamics with the boundary conditions based on the icosahedral group. The method is general and could be used for any molecular system with a point group symmetry. With this method, the dynamical and spatial intra and interpromotomer correlations can be studied at atomic levels. The technique is applicable to any virion with icosahedral symmetry. A sample calculation involving a geometry optimization of the human rhinovirus coat proteins is given to demonstrate the technique.

Molecular dynamics simulations of a zwitterionic bis(penicillamine) enkephalin derivative in 1.0 M saline solution have been performed. Two simulations produced essentially the same average results although they differed in the initial random placement of the salt ions. The dynamical and structural properties from the simulations were compared with those from a previous simulation of the peptide in pure water. The properties of the sodium and chloride ions were compared with those from a simulation of bulk salt solution. An inner-sphere complex between the peptide and the chloride ions was observed in which two to three chloride ions were associated with the NH3+ terminal hydrogen atoms. Several chlorides associated with more than one amide hydrogen simultaneously, and the resulting close chloride-chloride ion contacts were additionally stabilized by bridging water molecules. The sodium ions did not associate directly with the peptide but formed an outer-sphere complex surrounding the peptide-chloride ion complex. The effect of chloride ion association on the structure and dynamics of the peptide was investigated in detail. The spatial correlations between salt ions and the enkephalin derivative are discussed in relation to delta-opioid receptor binding. The implications that the observed ion effects have on our understanding of the Hofmeister series are also considered.

A class of triplex-forming oligodeoxyribonucleotides (TFOs) is described that can bind to naturally occurring sites in duplex DNA at physiological pH in the presence of magnesium. The data are consistent with a structure in which the TFO binds in the major groove of double-stranded DNA to form a three-stranded complex that is superficially similar to previously described triplexes. The distinguishing features of this class of triplex are that TFO binding apparently involves the formation of hydrogen-bonded G.GC and T.AT triplets and the TFO is bound antiparallel with respect to the more purine-rich strand of the underlying duplex. Triplex formation is described for targets in the promoter regions of three different genes: the human c-myc and epidermal growth factor receptor genes and the mouse insulin receptor gene. All three sites are relatively GC rich and have a high percentage of purine residues on one strand. DNase I footprinting shows that individual TFOs bind selectively to their target sites at pH 7.4-7.8 in the presence of millimolar concentrations of magnesium. Electrophoretic analysis of triplex formation indicates that specific TFOs bind to their target sites with apparent dissociation constants in the 10(-7)-10(-9) M range. Strand orientation of the bound TFOs was confirmed by attaching eosin or an iron-chelating group to one end of the TFO and monitoring the pattern of damage to the bound duplex DNA. Possible hydrogen-bonding patterns and triplex structures are discussed.

Quenched molecular dynamics is used as a conformational search technique for the constrained cyclic analog [D-Pen2,D-Pen5]enkephalin (DPDPE) in a continuum solvent. The results show a Gaussianlike distribution of conformations as a function of energy, unlike the distributions found for simple liquids which have sharp bands for different crystal forms and broad glasslike states are found. The lowest energy conformers have structural features in common with those obtained from constrained searches based on energy minimization. (Hruby, V. J., L.-F. Kao, B. M. Pettitt, and M. Karplus. 1988. J. Am. Chem. Soc. 110:3351-3359.) Many of the low energy configurations are amphiphilic with the carbonyl groups on one surface and the hydrophobic groups on the other. This supports the conclusions from the previous modeling study, which yielded amphiphilic structures as the most probable conformations of DPDPE when NOE data were included.

The methodological dependence of observed ion-peptide associations in molecular dynamics simulations is investigated. We compare the results from several simulations of a pentapeptide in explicit solvent and salt ions which differ in the their treatment of the long ranged electrostatic interactions. Results for both the Ewald and switching function techniques are presented. It was found that there were important differences between the two methods for the water dipole-dipole temporal and spatial correlations, total dipole moment fluctuations, and self-diffusion constants. Electrostatic potentials calculated in the region of the peptide are also used to illustrate the large differences that can arise from different treatments of the electrostatic interactions. It appears that the switching function distorts the molecular electrostatic potential experienced by the salt ions to such a degree that their behaviour becomes highly dependent on the initial conditions. In summary, the use of a switching function is not recommended for the simulation of ions and their interactions with biomolecules.

The grand molecular dynamics (GMD) method has been extended and applied to examine the density dependence of the chemical potential of a three-site water model. The method couples a classical system to a chemical potential reservoir of particles via an ansatz Lagrangian. Equilibrium properties such as structure and thermodynamics, as well as dynamic properties such as time correlations and diffusion constants, in open systems at a constant chemical potential, are preserved with this method. The average number of molecules converges in a reasonable amount of computational effort and provides a way to estimate the chemical potential of a given model force field.

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.

Recently, oligonucleotides have been shown to inhibit transcription in genes by triple helix or triplex formation in vitro and in vivo. A better understanding of the forces that stabilize triplex structures will be important in developing applications of this method of genetic medication to arbitrary sequences. Therefore, base pairings and strand orientations for homogeneous d(T.A.T)27 and d(C.G.G)27 triplexes were examined. The method was extended to triplex models formed by c-myc gene promoter region and complementary oligonucleotides. Templates of a single plane with three bases were constructed and used in a simple geometric replication based on experimental geometric parameters. Minimizations and quenched molecular dynamics simulations were performed on the model systems. The estimated accessibility of the major groove for counteraction coordination was obtained by calculating the effective accessible surface areas of backbone phosphate oxygen atoms. Free energy calculations of the solvation/desolvation penalty on single strands, duplexes, and the stereoisomeric triplexes have been performed. They were combined with corresponding enthalpic term so that the results could be discussed in a more realistic aspect. For d(T.A.T)27 triplexes, results from both the internal potential energy and solvation free energy calculations contribute to the experimentally known base pairing and strand orientation. Solvation is found to determine the strand orientation for d(C.G.G)27 triplexes with either Hoogsteen or reversed-Hoogsteen base pairing between the two purine strands being possible. We have compared the d(C.G.G)27 triplexes by computing the hydrogen-hydrogen distances which may be useful in verifying these models by future NMR/NOE studies. Using these homopolymers the orientation of oligonucleotides bound to the c-myc gene promoter site is shown to also be dominated by the forces of solvation.

We have used high-temperature quenched molecular dynamics calculations to investigate the conformational properties of tuftsin (Thr-Lys-Pro-Arg) in solution. Conformers obtained after quenching of the dynamical structures were sorted into families depending on their relative energies and backbone conformations. By examination of these families, several cyclic analogues of tuftsin were proposed and examined theoretically by further quenched dynamics simulations. Two of the four proposed analogues were found to adopt essentially identical conformations to that of linear tuftsin. It is suggested that these two derivatives (cyclo[Thr-Lys-Pro-Arg-Gly] and cyclo[Thr-Lys-Pro-Arg-Asp]) may be biologically active, and that the introduction of cyclic conformational constraints should help to reduce the entropic penalty to peptide binding.

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The electrostatic contributions to free energies of solvation of several small molecules have been calculated, treating the solvent as a statistical continuum. The computational method is based on solving the linearized Poisson-Boltzmann equation for the electrostatic potentials using the finite-difference scheme. A careful study of convergence indicates the importance of a fine grid spacing, as well as the short comings of rotational averaging. The computed free energies of solvation are in excellent agreement with the experimental results as well as the free energy perturbation calculations. The free energies of hydration of the natural nucleic acid bases are calculated and shown to be somewhat sensitive to charge model.

Alkali liquids intercalated in graphite are subject to a strong periodic host potential. We compare here two theories for the modulation induced in the alkali density that result in different approximations for higher-order correlations, with computer simulations and experimental data. We show these two theories-one based on a cumulant expansion, the other on an angular truncation of the Lovet-Mou-Buff equation-agree analytically in the limit of weak host potential and are numerically similar at high temperatures for a realistic potential.

Because of difficulties associated with experimental measurement techniques, the distribution of water density around many proteins is not well-resolved. We present, in this paper, a molecular dynamics approach to the general problem of comparing the instantaneous vs average view of protein hydration via a 150-ps simulation of metmyoglobin in an explicit aqueous environment. Densities as a function of position for both water and myoglobin were computed by time-averaging the volume fraction occupied at different positions in space. The picture so obtained challenges the view of hydration taken from accessible surface features related to the average structure. A detailed picture of protein hydration is given that includes significant surface penetration and transient channels, in conjunction with the accepted concepts of a-tightly bound partial layer of water on the surface near charged groups.

The potentials of mean force (pmfs) for rotation around the chi1 aromatic side-chain dihedrals of the zwitterionic bis-penicillamine enkephalin pentapeptide have been determined in both aqueous and saline solution. These side chains are known to be associated with the pharmacophore and their conformational populations are thought to be critical for activity. It is found that the association between chloride ions and the peptide in saline solution simulations has profound effects on the relative energies of the g-, g+, and t conformations, and also the barriers between them. Using the pmfs we have also calculated the respective Boltzmann-weighted 3J(alphabeta) vicinal coupling constants. The agreement between the calculated and experimentally determined coupling constants is poor for the pmf in pure water, but substantially improved for the pmf determined in saline solution. Reasons for these differences appear to be related to the experimental conditions.

Dynamics simulations of molecular systems are notoriously computationally intensive, Using parallel computers for these simulations is important for reducing their turnaround time. In this article we describe a parallelization of the simulation program CHARMM for the Intel iPSC/860, a distributed memory multiprocessor. In the parallelization, the computational work is partitioned among the processors for core calculations including the calculation of forces, the integration of equations of motion, the correction of atomic coordinates by constraint, and the generation and update of data structures used to compute nonbonded interactions. Processors coordinate their activity using synchronous communication to exchange data values. Key data structures used are partitioned among the processors in nearly equal pieces, reducing the memory requirement per node and making it possible to simulate larger molecular systems. We examine the effectiveness of the parallelization in the context of a case study of a realistic molecular system. While effective speedup was achieved for many of the dynamics calculations, other calculations fared less well due to growing communication costs for exchanging data among processors. The strategies we used are applicable to parallelization of similar molecular mechanics and dynamics programs for distributed memory multiprocessors.

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.

In this paper we report the initial steps in the development of a Monte Carlo method for evaluation of real-time Feynman path integrals for many-particle dynamics. The approach leads to Gaussian importance sampling for real-time dynamics in which the sampling function is short ranged due to the occurrence of Gaussian factors. These Gaussian factors result from the use of a generalization of our new discrete distributed approximating functions (DDAFs) to continuous distributed approximating functions (CDAFs) so as to replace the exact coordinate representation free-particle propagator by a CDAF-class, free-particle propagator which is highly banded. The envelope of the CDAF-class free propagator is the product of a bare Gaussian, exp[-(x'- x)2sigma2(0)/(2sigma4(0) + H2tau2/m2BAR)], with a shape polynomial in (x' - x)2, where sigma(0) is a width parameter at zero time (associated with the description of the wavepacket in terms of Hermite functions), tau is the time step (tau = t/N, where t is the total propagation time), and x and x' are any two configurations of the system. The bare Gaussians are used for Monte Carlo integration of a path integral for the survival probability of a Gaussian wavepacket in a Morse potential. The approach appears promising for real-time quantum Monte Carlo studies based on the time-dependent Schrodinger equation, the time-dependent von Neumann equation, and related equations.

We report the calculated characteristics of nonnatural triplex-forming oligonucleotide (TFO) bases recognizing base-pair reversals (TA -> AT) in a double-helical DNA sequence. Ab initio and molecular mechanics calculations have been carried out to characterize the geometric and energetic consequences at the base-pair reversal sites. We have estimated the free energies of solvation of the natural and proposed bases by solving the linearized Poisson-Boltzmann equation. The calculations indicate that the proposed TFO bases should bind with some specificity to the duplex. Implications of the strategy used in the context of molecular biology is discussed. (C) 1993 John Wiley & Sons, Inc.

Langevin dynamics on a potential of mean force energy surface is used to model the effects of aqueous solvent on the structure and dynamics of the alanine dipeptide. Conformational transition rates obtained by correlation function analysis and hazard plots from several simulations are compared. In particular, averages obtained over three 25-ns runs are compared with a single run of 100 ns. Rate constants for selected conformational transitions are also examined. For the conformational processes considered here (alpha to beta and the reverse), we observe two rates, one of which is only significant for simulations of more than 25 ns. On further decomposition of the rate process, it is shown that the two observed rates correspond to the individual rates for rotation around the phi and psi dihedrals. It is also shown that, for the conformational transitions investigated here, the transition process corresponds to an essentially uncorrelated motion of the two dihedral angles.

We report a novel conformational search procedure that is used to investigate the binding mechanism of a member of the WIN class of antiviral compounds. A simple hypothesis of important residues in the binding site based on differences in drug-free and drug-bound X-ray structures along with more elaborate models, ultimately including the entire virus, is considered. Our search method is a variant of slow-growth molecular dynamics used in free energy simulations and gives rise to local motion in the protein backbone of up to 3 angstrom. This technique involves the scaling of drug-protein interaction energies over time periods of 10-100 ps and gives rise to local motion in the protein backbone. In addition, we have used high-temperature dynamics with periodic quenching to generate low-energy conformations with backbone displacements in the crystallographic binding region of up to 7 angstrom from the native structure. Mechanism of binding, hydrogen-bond stabilization of active-site conformations, concerted drug-protein motions, and the mode of virion stabilization are addressed in relation to our ligand induced and high-temperature conformational search procedures. A loop-cap like mechanism is consistent with the results of our study. A large movement of the 'active-site'' residues is shown to be theoretically possible and provides a greater access for entry of the drug into its binding pocket than seen in the available crystal structures.

The bis(penicillamine) enkephalin, a small zwitterionic pentapeptide, has been studied in explicit 1.0 M sodium acetate solution with use of the molecular dynamics technique. During the simulation the association of multiple acetate ions with the positively charged N terminal region was observed. In addition, but to a far lesser extent, sodium ion binding to backbone carbonyl groups close to the negatively charged C terminus also occurred. Interesting individual events, such as the simultaneous binding of an acetate to a hydrogen of the N terminus and to backbone NH groups, were observed. Most often acetates only associated with the N terminal hydrogens. Subtle conformational changes in the peptide backbone were found as a consequence of acetate binding. These mechanistic observations are consistent with, and may be rationalized by, the known salting in and salting out properties of these ions and their relative positions in the Hofmeister (lyotropic) series.

We report the results of a 100-ps molecular dynamics simulation study of triple helical DNA with explicit water, counterions, and salt using periodic boundary conditions at 300 K. The simulation involved an antiparallel reverse-Hoogsteen-like homopolymeric CGG 7-mer triple helix, 837 water molecules, 21 Na+ ions, and 1 M NaCl. We have used the Ewald method to compute the electrostatic interactions. Specific ion and water associations as well as relative solvent and ion mobilities are reported. Specific patterns of ion and water molecule associations are found which are novel and may have implications for stability and recognition of triplex-forming oligonucleotides by duplex DNA. Exchanges of ions around neighboring phosphate were found to correspond to a concerted mechanism of displacement. Comparisons are made with available data from related systems.

An oligonucleotide hybrid is described which possesses two triple helix forming oligonucleotides which have been connected by a flexible polymeric linker chain. As a prototype, binding of this class of oligonucleotide to duplex DNA has been studied using a segment of the HSV-1 D-glycoprotein promoter, which possesses a pair of 12bp target sites for stable triple helix formation, separated by a duplex spacer region which is one helical turn long. Band shift and footprinting analysis show that such hybrids can bind to both 12bp elements simultaneously, if flexible linkers are included which are longer than 20 - 25 rotatable bonds. Molecular modeling confirms that a flexible polymeric linker as short as 22 rotatable bonds is enough to link the two distant segments of triple helix, providing that the linker element travels a path which is external to the helix grooves and parallel to the long helix axis.

The results of this theoretical study combining sequence analysis and minimization with integral equation liquid structural methods indicate that the local sequence context of a T-G wobble mismatch influences the local conformation of the helix, and that conformational alterations are correlated with mutational activity. Studies on the mismatch in four different 5' and 3' neighbor contexts indicate that the nature of the 5' base to the thymine of the mispair is probably the single most critical factor in determining the structural features that facilitate or discourage mutations. When cytosine is the 5' neighbor, the helix adopts a mostly BII conformation, whereas a 5' guanine preserves the canonical BI. Structures that vary little from the BI structure on the incorporation of the mismatch have sequences that correspond to lower rates of transition, whereas those with mostly BII conformations, have sequences with high mutation rates. Subtle variations in stacking patterns around the mismatch precipitate a structural Domino-effect, with a variety of changes in conformation. The helix opens at the mismatch with increased roll angle and propeller twist, causing the thymine to migrate into the major groove and the guanine into the minor groove, exposing the heteroatomic groups to the solvent in the major and minor grooves, respectively, and allowing for some unusual hydrogen bonds. These alterations show a tentative correlation with mutation rates, implying that stacking and structure around the mismatch are important features in the discrimination by proofreading activities of canonical W-C and wobble mismatch base pairs during replication-repair. Variations in the C1'-C1' distances, high propeller twists, changes in the electrostatic complementarity leading to unusual hydrogen bonding patterns probably all correlate with detectability.

An analysis of a molecular dynamics simulation of metmyoglobin in an explicit solvent environment of 3,128 water molecules has been performed. Both statics and dynamics of the protein-solvent interface are addressed in a comparison with experiment. Three-dimensional density distributions, temperature factors, and occupancy weights are computed for the solvent by using the trajectory coordinates. Analysis of the hydration leads to the localization of more than 500 hydration sites distributed into multiple layers of solvation located between 2.6 and 6.8 Angstrom from the atomic protein surface. After locating the local solvent density maxima or hydration sites we conclude that water molecules of hydration positions and hydration sites are distinct concepts. Both global and detailed properties of the hydration cluster around myoglobin are compared with recent neutron and X-ray data on myoglobin. Questions arising from differences between X-ray and neutron data concerning the locations of the protein-bound water are investigated. Analysis of water site differences found from X-ray and neutron experiments compared with our simulation shows that the simulation gives a way to unify the hydration picture given by the two experiments. (C) 1994 Wiley-Liss, Inc.

The dynamics of water at the protein-solvent interface is investigated through the analysis of a molecular dynamics simulation of metmyoglobin in explicit aqueous environment. Distribution implied dynamics, harmonic and quasiharmonic, are compared with the simulated macroscopic dynamics. The distinction between distinguishable solvent molecules and hydration sites developed in the previous paper is used. The simulated hydration region within 7 Angstrom from the protein surface is analyzed using a set of 551 hydration sites characterized by occupancy weights and temperature B-factors determined from the simulation trajectory. The precision of the isotropic harmonic and anisotropic harmonic models for the description of proximal solvent fluctuations is examined. Residence times and dipole reorientation times of water around the protein surface are compared with NMR and ESR results. A correlation between diffraction experiment quantities such as the occupancy weights and temperature factors and the residence and correlation times resulting from magnetic resonance experiments is found via comparison with simulation. (C) 1994 Wiley-Liss, Inc.

The solvent structure and dynamics around myoglobin is investigated at the microscopic level of detail by computer simulation. We analyze a molecular dynamics trajectory in terms of solvent mobility and probability distribution. Local events, occurring in the protein-solvent interfacial region, which are often masked by other approaches are thus revealed. Specifically, the local solvent mobility is greatly enhanced for certain locations at the protein surface and in its interior. In addition, a strong correlation between the solvent mobility and density emerges on both global and local scales. We propose a simple model where the solvent distribution measured perpendicularly to the protein surface is utilized to reconstruct the simulated network of hydration within 6 Angstrom from the protein surface with a relative error of only 17 model matches results obtained with more complicated models usually used in refinement procedures in x-ray and neutron experiments but with far fewer parameters. The dramatically improved correspondence between observed and calculated x-ray intensities at low resolution relative to other methods both confirms the validity of the approach used in the MD (molecular dynamics) simulations and allows the results of this study to be implemented in solvent studies on real systems.

The existence of a high-density phase separation for molecular and continuum solvent models of ion-water solutions are demonstrated using the DRISM/HNC theory. The molecular lever effects which influence solubility and the inability of continuum models to exhibit some of these effects are discussed. The general trends in experimental alkali halide solubilities are found to be consistent with the present model calculations. The dependence of the phase separation on ion size is found to be primarily entropic in nature.

The grand molecular dynamics (GMD) method has been extended and applied to examine the chemical potential and temperature dependence of a three-site water model in dense phase. The study demonstrates the utility of GMD in the study of phase transitions. Cuts through the phase diagram of water in terms of temperature, as well as excess chemical potential, are obtained. The density maximum of water just above freezing is well reproduced. High-pressure glass forms of solid ice are also examined.

Binding energies, intermolecular distances, and partial charges from ab initio studies of SO42- + H2O were used to develop a molecular mechanics model for SO42- in water. Structural, dynamic, and thermodynamic properties for the resulting model used in condensed-phase simulations agree well with experimental estimates. Thirteen waters are found to be present in the first solvation shell, and the residence time of these waters has been calculated to be 23 ps. The model anion has a free energy of solvation relative to xenon of -275 kcal mol(-1), which compares well with the experimental estimate of -266 kcal mol(-1).

Results for free energy, entropy, enthalpy and internal energy of solvation for monovalent ions in water have been studied by comparing DRISM theory results to those of RISM and ARISM theories. The greatly improved dielectric behavior in the DRISM case enabled the examination of realistically modeled salts at finite concentrations. The link between solvent structure and the entropy of solvent co-spheres was examined. Finally comparison with the Born free energy equation shows its virtues and flaws due to ignoring cavity formation and asymmetric solvation terms which together always contribute significantly to the free energy of hydration of ions.

An extended system Hamiltonian for the grand canonical ensemble that includes the number dependence of the ideal chemical potential is investigated. Use of the ideal contribution explicitly in the equations of motion provides simpler and more stable equations of motion than previous grand molecular dynamics methods. We find the equations of motion remain quite stable even in gaseous conditions where mean field treatments of the ideal contribution provide a trivial result. The equations of motion are solved in real variable space as opposed to using virtual variables. Application of this simulation method with a Lennard-Jones fluid in the gas, fluid and solid phases is demonstrated.

The molecular origins of the common ion effect and the salting out of nonpolar molecules from aqueous solutions are investigated. Thermodynamic stability criteria for a common ion mixture in a polar solvent are derived. Kirkwood-Buff statistical thermodynamics is used to make the connection with the microscopic pair correlation functions. The observed sensitivity of the compositional stability with respect to ionic strength indicates that a demixing transition is the primary cause of the instability for the common ion effect for our model Lennard-Jones plus Coulomb Hamiltonian.

Currently applied models for the treatment of solvent in biomolecular systems are reviewed. Solv