A novel scoring function to estimate protein-ligand binding affinities has been developed and implemented as the Glide 4.0 XP scoring function and docking protocol. In addition to unique water desolvation energy terms, protein-ligand structural motifs leading to enhanced binding affinity are included: (1) hydrophobic enclosure where groups of lipophilic ligand atoms are enclosed on opposite faces by lipophilic protein atoms, (2) neutral-neutral single or correlated hydrogen bonds in a hydrophobically enclosed environment, and (3) five categories of charged-charged hydrogen bonds. The XP scoring function and docking protocol have been developed to reproduce experimental binding affinities for a set of 198 complexes (RMSDs of 2.26 and 1.73 kcal/mol over all and well-docked ligands, respectively) and to yield quality enrichments for a set of fifteen screens of pharmaceutical importance. Enrichment results demonstrate the importance of the novel XP molecular recognition and water scoring in separating active and inactive ligands and avoiding false positives.

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Extra Precision Glide: Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein-Ligand Complexes

The fate of chemical and radioactive wastes in the environment is related to the ability of natural phases to attenuate and immobilize contaminants through chemical sorption and precipitation processes. Our understanding of these complex processes at the atomic level is provided by a few experimental and analytical methods such as X-ray absorption and NMR spectroscopies. However, due to complexities in the structure and composition of clay and other hydrated minerals, and the inherent uncertainties of the experimental methods, it is important to apply theoretical molecular models for a fundamental atomic-level understanding, interpretation, and prediction of these phenomena. In this effort, we have developed a general force field, CLAYFF, suitable for the simulation of hydrated and multicomponent mineral systems and their interfaces with aqueous solutions. Interatomic potentials were derived from parametrizations incorporating structural and spectroscopic data for a variety of simple hydrated compounds. A...

Molecular Models of Hydroxide, Oxyhydroxide, and Clay Phases and the Development of a General Force Field

Structure and nanostructure in ionic liquids.

Numerical Initial Value Problems in Ordinary Differential Equations

Aqueous surfaces and interfaces are important in many physical, chemical, and biological processes in our world. The adsorption, dissolution, and reaction of atmospheric gases at the surfaces of atmospheric aerosols and oceanic waters play a key role in the composition of our atmosphere and the sustainability of plant and animal species in land waters. The transport and exchange of ions and solutes across the interface between an aqueous phase and hydrophobic biomolecular assemblies underlies some of the most important processes in living plants and animals. Membrane formation, protein folding, and micelle formation all involve, and are often controlled by, bonding interactions with water molecules at their surfaces. The unique physical, chemical, and biological properties of aqueous surfaces arise from the strong hydrogen bonding that occurs between water molecules and the asymmetry in this otherwise tetrahedral bonding coordination that results from the termination of the bulk water phase. Although there has been increased experimental and theoretical effort in recent years focused on developing a molecular picture of the structure and bonding of water layers to other solid, liquid, and gaseous media, consensus on the details of interfacial bonding has been slow or nonexistent in many areas. The adsorption of ions, surfactants, and solute molecules at these interfaces adds a level of complexity to the Geraldine Richmond holds the Richard M. and Patricia H. Noyes Professor of Chemistry position at the University of Oregon. She received her Ph.D. degree under the mentorship of George Pimentel at the University of California, Berkeley, in 1980. From 1980 to 1985 she was on the faculty at Bryn Mawr College and moved to the University of Oregon in 1985 as an associate professor. Richmond is recognized for her fundamental studies of the structure, dynamics, and bonding characteristics of surfaces and interfaces. Her research group uses a combination of linear and nonlinear optical methods, thermodynamic measurements, and theory to characterize interactions at aqueous surfaces, metal and semiconductor surfaces in contact with liquids and adsorbates, and liquid/liquid interfaces. Richmond has received several recent honors for these studies including the 2002 ACS Spectrochemical Analysis Award, the 2001 Oregon Scientist of the Year, and the 1996 Olin-Garvan Medal of the ACS and has been a Fellow of the American Physical Society since 1993. 2693 Chem. Rev. 2002, 102, 2693−2724

Molecular bonding and interactions at aqueous surfaces as probed by vibrational sum frequency spectroscopy.

We calculate the mobilities ui of the metal cations Li+, Na+, K+, Rb+, Cs+, and Ca2+ and the halides F-, Cl-, Br-, and I- at infinite dilution by molecular dynamics simulation using the SPC/E model for water at 25 °C and a reaction field for the long-range interactions. The ion mobilities show the same trends as the experimental results with distinct maxima for cations and anions. The mobilities (defined by ui = Di/kT) of the corresponding uncharged species are also determined by simulation and are in qualitative agreement with Stokes' law. The mobilities of Li+, Na+, K+, Rb+ and F- increase on discharge, whereas Cl, Br, and I have smaller mobilities than the corresponding anions. The mobility of the fictitious I+ ion, which differs from I- only in its charge, lies between that of I- and I in the order uI < uI+ < uI−. The residence time of water in the first solvation shell of small cations (Li+ and Na+) and Ca2+ decreases when the ions are discharged, while the opposite is observed on neutralizing I-, su...

http://omh.umeche.maine.edu/pdfs/JPCB_102_4193_98.pdf

Solvent Structure, Dynamics, and Ion Mobility in Aqueous Solutions at 25 °C

The structure and dynamics of liquid water at the interface with three solid surfaces has been investigated via molecular dynamics simulation. The three surfaces include a flat hydrophobic surface, an atomically rough hydrophobic surface, and a contrasting, hydrophilic, fully hydroxylated silica surface. The results of analysis show that, as expected, the solvent near each of the two hydrophobic surfaces behaves essentially equivalently, with loss of hydrogen bonding at the interface. For the hydroxylated surface, surface–solvent hydrogen bonding is stronger than interactions in the bulk solvent, with the nearest solvent layer interacting specifically with up to three surface hydroxyl groups. Nevertheless, distinct structural perturbation of the solvent extends in every case no more than about 10 A from the surface, and the perturbation is only strong in the immediate solvation layer. Furthermore, the corresponding dynamical perturbation of the solvent, as measured by the diffusion rates and reorientation...

A comparison of the structure and dynamics of liquid water at hydrophobic and hydrophilic surfaces—a molecular dynamics simulation study

We present results of computer simulations of the mobilities of the alkali metal ions (Li+, Na+, K+, Rb+, and Cs+) and the halides (F-, Cl-, Br-, and I-) at 25 °C using the SPC/E model for water and ion−water parameters fitted to the binding energies of small clusters of ions. A simple truncation of the ion−water and water−water potentials was used, and the mobilities calculated from the mean square displacement and the velocity autocorrelation functions, respectively, were found to be in good agreement with each other. The calculations demonstrate, for the first time, cation and anion mobilities that fall on separate curves, as functions of ion size, with distinct maxima. This is in complete accord with experimental trends observed in water at 25 °C. The cation mobilities are also in better agreement with the measured values than the calculations done earlier (J. Chem. Phys. 1994, 101, 6964) using the TIP4P model. The mobilities of the halides calculated here for the SPC/E model are however slightly lowe...

Molecular Dynamics Simulation of Ion Mobility. 2. Alkali Metal and Halide Ions Using the SPC/E Model for Water at 25 °C†

We describe a series of molecular dynamics simulations performed on model cation‐water systems at 25 °C representing the behavior of Li+, Na+, K+, Rb+, and Cs+ in an electric field of 1.0 V/nm and in its absence. The TIP4P model was used for water and TIPS potentials were adapted for the ion‐water interactions. The structure of the surrounding water molecules around the cations was found to be independent of the applied electric field. Some of the dynamic properties, such as the velocity and force autocorrelation functions of the cations, are also field independent. However, the mean‐square displacements of the cations, their average drift velocities, and the distances traveled by them are field dependent. The mobilities of the cations calculated directly from the drift velocity or the distance traveled by the ion are in good agreement with each other and they are in satisfactory agreement with the mobilities determined from the mean‐square displacement and the velocity autocorrelation function in the absence of the field. They also show the same trends with ionic radii that are observed experimentally; the magnitudes are, however, smaller than the experimental values in real water by almost a factor of 2. It is found that the water molecules in the first solvation shell around the small Li+ ion are stuck to the ion and move with it as an entity for about 190 ps, while the water molecules around the Na+ ion remain for 35 ps, and those around the large cations stay for 8–11 ps before significant exchange with the surroundings occurs. The picture emerging from this analysis is that of a solvated cation whose mobility is determined by its size as well as the static and dynamic properties of its solvation sheath and the surrounding water. The classical solventberg model describes the mobility of Li+ ions in water adequately but not those of the other ions.

Molecular dynamics simulation of ionic mobility. i: alkali metal cations in water at 25 c

Hydrogen (H(+)) and hydroxide (OH(-)) ions in aqueous solution have anomalously large diffusion coefficients, and the mobility of the H(+) ion is nearly twice that of the OH(-) ion We describe molecular dynamics simulations of a dissociating model for liquid water based on scaling the interatomic potential for water developed by Ojamae-Shavitt-Singer from ab initio studies at the MP2 level We use the scaled model to study proton transfer that occurs in the transport of hydrogen and hydroxide ions in acidic and basic solutions containing 215 water molecules The model supports the Eigen-Zundel-Eigen mechanism of proton transfer in acidic solutions and the transient hyper-coordination of the hydroxide ion in weakly basic solutions at room temperature The free energy barriers for proton transport are low indicating significant proton delocalization accompanying proton transfer in acidic and basic solutions The reorientation dynamics of the hydroxide ion suggests changes in the proportions of hyper-coordinated species with temperature The mobilities of the hydrogen and hydroxide ions and their temperature dependence between 0 and 50 °C are in excellent agreement with experiment and the reasons for the large difference in the mobilities of the two ions are discussed The model and methods described provide a novel approach to studies of liquid water, proton transfer, and acid-base reactions in aqueous solutions, channels, and interfaces

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Song Hi Lee

Papers

Solvent Structure, Dynamics, and Ion Mobility in Aqueous Solutions at 25 °C

A comparison of the structure and dynamics of liquid water at hydrophobic and hydrophilic surfaces—a molecular dynamics simulation study

Molecular Dynamics Simulation of Ion Mobility. 2. Alkali Metal and Halide Ions Using the SPC/E Model for Water at 25 °C†

Molecular dynamics simulation of ionic mobility. i: alkali metal cations in water at 25 c

Proton transfer and the mobilities of the H+ and OH- ions from studies of a dissociating model for water.