The Experts below are selected from a list of 255 Experts worldwide ranked by ideXlab platform
Julien Michel - One of the best experts on this subject based on the ideXlab platform.
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Assessment of Hydration Thermodynamics at Protein Interfaces with Grid Cell Theory.
Journal of Physical Chemistry B, 2016Co-Authors: Georgios Gerogiokas, Richard H. Henchman, Michelle W. Y. Southey, Michael P. Mazanetz, Michael J. Bodkin, Alexander Heifetz, Julien MichelAbstract:Molecular dynamics simulations have been analyzed with the Grid Cell Theory (GCT) method to spatially resolve the binding enthalpies and entropies of water molecules at the interface of 17 structurally diverse proteins. Correlations between computed energetics and structural descriptors have been sought to facilitate the development of simple models of protein hydration. Little correlation was found between GCT-computed binding enthalpies and continuum electrostatics calculations. A simple count of contacts with functional groups in charged amino acids correlates well with enhanced water stabilization, but the stability of water near hydrophobic and polar residues depends markedly on its coordination environment. The positions of X-ray-resolved water molecules correlate with computed high-density hydration sites, but many unresolved waters are significantly stabilized at the protein surfaces. A defining characteristic of ligand-binding pockets compared to nonbinding pockets was a greater solvent-accessibl...
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Correction: Evaluation of water displacement energetics in protein binding sites with grid Cell Theory
Physical Chemistry Chemical Physics, 2015Co-Authors: Georgios Gerogiokas, Michelle W. Y. Southey, Michael P. Mazanetz, A. Hefeitz, Michael J. Bodkin, Julien MichelAbstract:Correction for ‘Evaluation of water displacement energetics in protein binding sites with grid Cell Theory’ by G. Gerogiokas et al., Phys. Chem. Chem. Phys., 2015, 17, 8416–8426.
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Evaluation of water displacement energetics in protein binding sites with grid Cell Theory.
Physical Chemistry Chemical Physics, 2015Co-Authors: Georgios Gerogiokas, Michelle W. Y. Southey, Michael P. Mazanetz, Michael J. Bodkin, Alexander Heifetz, Julien MichelAbstract:Excess free energies, enthalpies and entropies of water in protein binding sites were computed via classical simulations and Grid Cell Theory (GCT) analyses for three pairs of congeneric ligands in complex with the proteins scytalone dehydratase, p38α MAP kinase and EGFR kinase respectively. Comparative analysis is of interest since the binding modes for each ligand pair differ in the displacement of one binding site water molecule, but significant variations in relative binding affinities are observed. Protocols that vary in their use of restraints on protein and ligand atoms were compared to determine the influence of protein–ligand flexibility on computed water structure and energetics, and to assess protocols for routine analyses of protein–ligand complexes. The GCT-derived binding affinities correctly reproduce experimental trends, but the magnitude of the predicted changes in binding affinities is exaggerated with respect to results from a previous Monte Carlo Free Energy Perturbation study. Breakdown of the GCT water free energies into enthalpic and entropic components indicates that enthalpy changes dominate the observed variations in energetics. In EGFR kinase GCT analyses revealed that replacement of a pyrimidine by a cyanopyridine perturbs water energetics up three hydration shells away from the ligand.
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Evaluation of Host–Guest Binding Thermodynamics of Model Cavities with Grid Cell Theory
Journal of Chemical Theory and Computation, 2014Co-Authors: Julien Michel, Georgios Gerogiokas, Richard H. Henchman, Michelle W. Y. Southey, Michael P. MazanetzAbstract:A previously developed Cell Theory model of liquid water was used to evaluate the excess thermodynamic properties of confined clusters of water molecules. The results are in good agreement with reference thermodynamic integration calculations, suggesting that the model is adequate to probe the thermodynamic properties of water at interfaces or in cavities. Next, the grid Cell Theory (GCT) method was applied to elucidate the thermodynamic signature of nonpolar association for a range of idealized host–guest systems. Polarity and geometry of the host cavities were systematically varied, and enthalpic and entropic solvent components were spatially resolved for detailed graphical analyses. Perturbations in the thermodynamic properties of water molecules upon guest binding are restricted to the immediate vicinity of the guest in solvent-exposed cavities, whereas longer-ranged perturbations are observed in buried cavities. Depending on the polarity and geometry of the host, water displacement by a nonpolar gues...
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Prediction of Small Molecule Hydration Thermodynamics with Grid Cell Theory.
Journal of Chemical Theory and Computation, 2013Co-Authors: Georgios Gerogiokas, Gaetano Calabro, Richard H. Henchman, Michelle W. Y. Southey, Julien MichelAbstract:An efficient methodology has been developed to quantify water energetics by analysis of explicit solvent molecular simulations of organic and biomolecular systems. The approach, grid Cell Theory (GCT), relies on a discretization of the Cell Theory methodology on a three-dimensional grid to spatially resolve the density, enthalpy, and entropy of water molecules in the vicinity of solute(s) of interest. Entropies of hydration are found to converge more efficiently than enthalpies of hydration. GCT predictions of free energies of hydration on a data set of small molecules are strongly correlated with thermodynamic integration predictions. Agreement with the experiment is comparable for both approaches. A key advantage of GCT is its ability to provide from a single simulation insightful graphical analyses of spatially resolved components of the enthalpies and entropies of hydration.
P.a. Monson - One of the best experts on this subject based on the ideXlab platform.
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An application of Cell Theory to molecular models of n-alkane solids
Molecular Physics, 2000Co-Authors: Ap P. Malanoski, Carlos Vega, P.a. MonsonAbstract:Solid phase properties for hard sphere chain molecular models of n-alkanes are calculated using the Cell Theory, and a numerical method for implementation of Cell Theory for chain molecules is described. Good agreement with Monte Carlo simulations for solid phase properties is obtained from the Theory. By using Cell Theory for the solid phase and an equation of state for the fluid phase, solid-phase equilibrium can be calculated. The predictions are in quite good agreement with Monte Carlo simulation results. Cell Theory is used to assess the impact of an approximate treatment used in earlier work for the effect of the temperature dependence of the molecular flexibility upon the solid phase properties of a hard chain model with a realistic torsional potential.
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Solid–fluid phase equilibrium for single component and binary Lennard‐Jones systems: A Cell Theory approach
Journal of Chemical Physics, 1996Co-Authors: X. Cottin, P.a. MonsonAbstract:We consider the application of the Cell Theory to single component and binary Lennard‐Jones solids. We calculate solid phase properties and solid–fluid equilibrium using the Cell Theory for the solid phase and an equation of state for the fluid phase. In the single component case the thermodynamic properties as well as the solid–fluid phase diagram predicted by the Theory are in quite good agreement with Monte Carlo simulation results. The introduction of correlations between the motions of nearest neighbor particles into the Cell Theory in a fashion suggested by Barker significantly improves the agreement. For binary Lennard‐Jones 12‐6 mixtures the predictions of the Theory are compared with experimental data for mixtures forming substitutionally disordered solid solutions involving argon, krypton and methane. The Theory correctly predicts the form of the phase diagram but the quantitative predictions are quite sensitive to the choice of potential parameters. The shape of the phase diagram is similar to ...
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A Cell Theory for solid solutions: Application to hard sphere mixtures
Journal of Chemical Physics, 1993Co-Authors: X. Cottin, P.a. MonsonAbstract:We consider the application of the Cell Theory to the properties of solid solutions. In contrast with previous implementations of the Cell Theory for mixtures we include all types of Cell partition function which arise from different nearest neighbor compositions and arrangements of the nearest neighbors, a feature which is necessary for a realistic treatment of substitutionally disordered solid solutions with components of different molecular sizes. An efficient algorithm for the simultaneous calculation of all contributing Cell partition functions is presented. The Theory is applied to the properties of binary hard sphere mixtures forming substitutionally disordered solid solutions. Solid–fluid equilibria are determined by using the Cell Theory for the solid phase together with an accurate fluid phase equation of state. Good agreement with Monte Carlo simulations is obtained.
Georgios Gerogiokas - One of the best experts on this subject based on the ideXlab platform.
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Assessment of Hydration Thermodynamics at Protein Interfaces with Grid Cell Theory.
Journal of Physical Chemistry B, 2016Co-Authors: Georgios Gerogiokas, Richard H. Henchman, Michelle W. Y. Southey, Michael P. Mazanetz, Michael J. Bodkin, Alexander Heifetz, Julien MichelAbstract:Molecular dynamics simulations have been analyzed with the Grid Cell Theory (GCT) method to spatially resolve the binding enthalpies and entropies of water molecules at the interface of 17 structurally diverse proteins. Correlations between computed energetics and structural descriptors have been sought to facilitate the development of simple models of protein hydration. Little correlation was found between GCT-computed binding enthalpies and continuum electrostatics calculations. A simple count of contacts with functional groups in charged amino acids correlates well with enhanced water stabilization, but the stability of water near hydrophobic and polar residues depends markedly on its coordination environment. The positions of X-ray-resolved water molecules correlate with computed high-density hydration sites, but many unresolved waters are significantly stabilized at the protein surfaces. A defining characteristic of ligand-binding pockets compared to nonbinding pockets was a greater solvent-accessibl...
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Correction: Evaluation of water displacement energetics in protein binding sites with grid Cell Theory
Physical Chemistry Chemical Physics, 2015Co-Authors: Georgios Gerogiokas, Michelle W. Y. Southey, Michael P. Mazanetz, A. Hefeitz, Michael J. Bodkin, Julien MichelAbstract:Correction for ‘Evaluation of water displacement energetics in protein binding sites with grid Cell Theory’ by G. Gerogiokas et al., Phys. Chem. Chem. Phys., 2015, 17, 8416–8426.
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Evaluation of water displacement energetics in protein binding sites with grid Cell Theory.
Physical Chemistry Chemical Physics, 2015Co-Authors: Georgios Gerogiokas, Michelle W. Y. Southey, Michael P. Mazanetz, Michael J. Bodkin, Alexander Heifetz, Julien MichelAbstract:Excess free energies, enthalpies and entropies of water in protein binding sites were computed via classical simulations and Grid Cell Theory (GCT) analyses for three pairs of congeneric ligands in complex with the proteins scytalone dehydratase, p38α MAP kinase and EGFR kinase respectively. Comparative analysis is of interest since the binding modes for each ligand pair differ in the displacement of one binding site water molecule, but significant variations in relative binding affinities are observed. Protocols that vary in their use of restraints on protein and ligand atoms were compared to determine the influence of protein–ligand flexibility on computed water structure and energetics, and to assess protocols for routine analyses of protein–ligand complexes. The GCT-derived binding affinities correctly reproduce experimental trends, but the magnitude of the predicted changes in binding affinities is exaggerated with respect to results from a previous Monte Carlo Free Energy Perturbation study. Breakdown of the GCT water free energies into enthalpic and entropic components indicates that enthalpy changes dominate the observed variations in energetics. In EGFR kinase GCT analyses revealed that replacement of a pyrimidine by a cyanopyridine perturbs water energetics up three hydration shells away from the ligand.
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Evaluation of Host–Guest Binding Thermodynamics of Model Cavities with Grid Cell Theory
Journal of Chemical Theory and Computation, 2014Co-Authors: Julien Michel, Georgios Gerogiokas, Richard H. Henchman, Michelle W. Y. Southey, Michael P. MazanetzAbstract:A previously developed Cell Theory model of liquid water was used to evaluate the excess thermodynamic properties of confined clusters of water molecules. The results are in good agreement with reference thermodynamic integration calculations, suggesting that the model is adequate to probe the thermodynamic properties of water at interfaces or in cavities. Next, the grid Cell Theory (GCT) method was applied to elucidate the thermodynamic signature of nonpolar association for a range of idealized host–guest systems. Polarity and geometry of the host cavities were systematically varied, and enthalpic and entropic solvent components were spatially resolved for detailed graphical analyses. Perturbations in the thermodynamic properties of water molecules upon guest binding are restricted to the immediate vicinity of the guest in solvent-exposed cavities, whereas longer-ranged perturbations are observed in buried cavities. Depending on the polarity and geometry of the host, water displacement by a nonpolar gues...
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Prediction of Small Molecule Hydration Thermodynamics with Grid Cell Theory.
Journal of Chemical Theory and Computation, 2013Co-Authors: Georgios Gerogiokas, Gaetano Calabro, Richard H. Henchman, Michelle W. Y. Southey, Julien MichelAbstract:An efficient methodology has been developed to quantify water energetics by analysis of explicit solvent molecular simulations of organic and biomolecular systems. The approach, grid Cell Theory (GCT), relies on a discretization of the Cell Theory methodology on a three-dimensional grid to spatially resolve the density, enthalpy, and entropy of water molecules in the vicinity of solute(s) of interest. Entropies of hydration are found to converge more efficiently than enthalpies of hydration. GCT predictions of free energies of hydration on a data set of small molecules are strongly correlated with thermodynamic integration predictions. Agreement with the experiment is comparable for both approaches. A key advantage of GCT is its ability to provide from a single simulation insightful graphical analyses of spatially resolved components of the enthalpies and entropies of hydration.
Jeanfrancois Lambert - One of the best experts on this subject based on the ideXlab platform.
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the chiaroscuro stem Cell a unified stem Cell Theory
Blood, 2002Co-Authors: Peter J Quesenberry, Gerald A Colvin, Jeanfrancois LambertAbstract:Hematopoiesis has been considered hierarchical in nature, but recent data suggest that the system is not hierarchical and is, in fact, quite functionally plastic. Existing data indicate that engraftment and progenitor phenotypes vary inversely with Cell cycle transit and that gene expression also varies widely. These observations suggest that there is no progenitor/stem Cell hierarchy, but rather a reversible continuum. This may, in turn, be dependent on shifting chromatin and gene expression with Cell cycle transit. If the phenotype of these primitive marrow Cells changes from engraftable stem Cell to progenitor and back to engraftable stem Cell with cycle transit, then this suggests that the identity of the engraftable stem Cell may be partially masked in nonsynchronized marrow Cell populations. A general model indicates a marrow Cell that can continually change its surface receptor expression and thus responds to external stimuli differently at different points in the Cell cycle.
Richard H. Henchman - One of the best experts on this subject based on the ideXlab platform.
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Assessment of Hydration Thermodynamics at Protein Interfaces with Grid Cell Theory.
Journal of Physical Chemistry B, 2016Co-Authors: Georgios Gerogiokas, Richard H. Henchman, Michelle W. Y. Southey, Michael P. Mazanetz, Michael J. Bodkin, Alexander Heifetz, Julien MichelAbstract:Molecular dynamics simulations have been analyzed with the Grid Cell Theory (GCT) method to spatially resolve the binding enthalpies and entropies of water molecules at the interface of 17 structurally diverse proteins. Correlations between computed energetics and structural descriptors have been sought to facilitate the development of simple models of protein hydration. Little correlation was found between GCT-computed binding enthalpies and continuum electrostatics calculations. A simple count of contacts with functional groups in charged amino acids correlates well with enhanced water stabilization, but the stability of water near hydrophobic and polar residues depends markedly on its coordination environment. The positions of X-ray-resolved water molecules correlate with computed high-density hydration sites, but many unresolved waters are significantly stabilized at the protein surfaces. A defining characteristic of ligand-binding pockets compared to nonbinding pockets was a greater solvent-accessibl...
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Evaluation of Host–Guest Binding Thermodynamics of Model Cavities with Grid Cell Theory
Journal of Chemical Theory and Computation, 2014Co-Authors: Julien Michel, Georgios Gerogiokas, Richard H. Henchman, Michelle W. Y. Southey, Michael P. MazanetzAbstract:A previously developed Cell Theory model of liquid water was used to evaluate the excess thermodynamic properties of confined clusters of water molecules. The results are in good agreement with reference thermodynamic integration calculations, suggesting that the model is adequate to probe the thermodynamic properties of water at interfaces or in cavities. Next, the grid Cell Theory (GCT) method was applied to elucidate the thermodynamic signature of nonpolar association for a range of idealized host–guest systems. Polarity and geometry of the host cavities were systematically varied, and enthalpic and entropic solvent components were spatially resolved for detailed graphical analyses. Perturbations in the thermodynamic properties of water molecules upon guest binding are restricted to the immediate vicinity of the guest in solvent-exposed cavities, whereas longer-ranged perturbations are observed in buried cavities. Depending on the polarity and geometry of the host, water displacement by a nonpolar gues...
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Prediction of Small Molecule Hydration Thermodynamics with Grid Cell Theory.
Journal of Chemical Theory and Computation, 2013Co-Authors: Georgios Gerogiokas, Gaetano Calabro, Richard H. Henchman, Michelle W. Y. Southey, Julien MichelAbstract:An efficient methodology has been developed to quantify water energetics by analysis of explicit solvent molecular simulations of organic and biomolecular systems. The approach, grid Cell Theory (GCT), relies on a discretization of the Cell Theory methodology on a three-dimensional grid to spatially resolve the density, enthalpy, and entropy of water molecules in the vicinity of solute(s) of interest. Entropies of hydration are found to converge more efficiently than enthalpies of hydration. GCT predictions of free energies of hydration on a data set of small molecules are strongly correlated with thermodynamic integration predictions. Agreement with the experiment is comparable for both approaches. A key advantage of GCT is its ability to provide from a single simulation insightful graphical analyses of spatially resolved components of the enthalpies and entropies of hydration.
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Classical and quantum gibbs free energies and phase behavior of water using simulation and Cell Theory.
Journal of Physical Chemistry B, 2008Co-Authors: Martin Klefas-stennett, Richard H. HenchmanAbstract:A method to calculate the classical and quantum free energy of a liquid from a computer simulation by using Cell Theory [J. Chem. Phys. 2007, 126, 064504] is tested for liquid water and ice Ih against experiment as a function of temperature. This fast and efficient method reproduces reasonably well the experimental values of entropy, enthalpy, and free energy of a liquid across the supercooled, stable, and superheated range of temperatures considered. There are small differences between classical and quantum results of water at 298 K, necessitating a small correction term to reproduce water’s enthalpy of vaporisation. Only at higher temperatures is entropy underestimated by up to 9 J K−1 mol−1 as verified by thermodynamic integration calculations. Satisfactory agreement for ice, however, is only obtained by using the quantum formulation. Even then, at higher temperatures, the entropies exceed experiment by up to 15 J K−1 mol−1. Further insight into the quantum nature of water is provided by inspecting the...
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Free energy of liquid water from a computer simulation via Cell Theory.
Journal of Chemical Physics, 2007Co-Authors: Richard H. HenchmanAbstract:A method to calculate the free energy of water from computer simulation is presented. Based on Cell Theory, it approximates the potential energy surface sampled in the simulation by an anisotropic six-dimensional harmonic potential to model the three hindered translations and three hindered rotations of a single rigid water molecule. The potential is parametrized from the magnitude of the forces and torques measured in the simulation. The entropy of these six harmonic oscillators is calculated and summed with a conformational term to give the total entropy. Combining this with the simulation enthalpy yields the free energy. The six water models examined are TIP3P, SPC, TIP4P, SPC/E, TIP5P, and TIP4P-Ew. The results reproduce experiment well: free energies for all models are within 1.6kJmol−1 and entropies are within 3.6JK−1mol−1. Approximately two-thirds of the entropy comes from translation, a third from rotation, and 5% from conformation. Vibrational frequencies match those in the experimental infrared ...