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Sample records for all-atom explicit solvent

  1. Variational Optimization of an All-Atom Implicit Solvent Force Field to Match Explicit Solvent Simulation Data

    PubMed Central

    Bottaro, Sandro; Lindorff-Larsen, Kresten; Best, Robert B.

    2013-01-01

    The development of accurate implicit solvation models with low computational cost is essential for addressing many large-scale biophysical problems. Here, we present an efficient solvation term based on a Gaussian solvent-exclusion model (EEF1) for simulations of proteins in aqueous environment, with the primary aim of having a good overlap with explicit solvent simulations, particularly for unfolded and disordered states – as would be needed for multiscale applications. In order to achieve this, we have used a recently proposed coarse-graining procedure based on minimization of an entropy-related objective function to train the model to reproduce the equilibrium distribution obtained from explicit water simulations. Via this methodology, we have optimized both a charge screening parameter and a backbone torsion term against explicit solvent simulations of an α-helical and a β-stranded peptide. The performance of the resulting effective energy function, termed EEF1-SB, is tested with respect to the properties of folded proteins, the folding of small peptides or fast-folding proteins, and NMR data for intrinsically disordered proteins. The results show that EEF1-SB provides a reasonable description of a wide range of systems, but its key advantage over other methods tested is that it captures very well the structure and dimension of disordered or weakly structured peptides. EEF1-SB is thus a computationally inexpensive (~ 10 times faster than Generalized-Born methods) and transferable approximation for treating solvent effects. PMID:24748852

  2. COFFDROP: A Coarse-Grained Nonbonded Force Field for Proteins Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of Amino Acids

    PubMed Central

    2015-01-01

    We describe the derivation of a set of bonded and nonbonded coarse-grained (CG) potential functions for use in implicit-solvent Brownian dynamics (BD) simulations of proteins derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acids. Bonded potential functions were derived from 1 μs MD simulations of each of the 20 canonical amino acids, with histidine modeled in both its protonated and neutral forms; nonbonded potential functions were derived from 1 μs MD simulations of every possible pairing of the amino acids (231 different systems). The angle and dihedral probability distributions and radial distribution functions sampled during MD were used to optimize a set of CG potential functions through use of the iterative Boltzmann inversion (IBI) method. The optimized set of potential functions—which we term COFFDROP (COarse-grained Force Field for Dynamic Representation Of Proteins)—quantitatively reproduced all of the “target” MD distributions. In a first test of the force field, it was used to predict the clustering behavior of concentrated amino acid solutions; the predictions were directly compared with the results of corresponding all-atom explicit-solvent MD simulations and found to be in excellent agreement. In a second test, BD simulations of the small protein villin headpiece were carried out at concentrations that have recently been studied in all-atom explicit-solvent MD simulations by Petrov and Zagrovic (PLoS Comput. Biol.2014, 5, e1003638). The anomalously strong intermolecular interactions seen in the MD study were reproduced in the COFFDROP simulations; a simple scaling of COFFDROP’s nonbonded parameters, however, produced results in better accordance with experiment. Overall, our results suggest that potential functions derived from simulations of pairwise amino acid interactions might be of quite broad applicability, with COFFDROP likely to be especially useful for modeling unfolded or intrinsically

  3. Parametrization of Backbone Flexibility in a Coarse-Grained Force Field for Proteins (COFFDROP) Derived from All-Atom Explicit-Solvent Molecular Dynamics Simulations of All Possible Two-Residue Peptides.

    PubMed

    Frembgen-Kesner, Tamara; Andrews, Casey T; Li, Shuxiang; Ngo, Nguyet Anh; Shubert, Scott A; Jain, Aakash; Olayiwola, Oluwatoni J; Weishaar, Mitch R; Elcock, Adrian H

    2015-05-12

    Recently, we reported the parametrization of a set of coarse-grained (CG) nonbonded potential functions, derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acid pairs and designed for use in (implicit-solvent) Brownian dynamics (BD) simulations of proteins; this force field was named COFFDROP (COarse-grained Force Field for Dynamic Representations Of Proteins). Here, we describe the extension of COFFDROP to include bonded backbone terms derived from fitting to results of explicit-solvent MD simulations of all possible two-residue peptides containing the 20 standard amino acids, with histidine modeled in both its protonated and neutral forms. The iterative Boltzmann inversion (IBI) method was used to optimize new CG potential functions for backbone-related terms by attempting to reproduce angle, dihedral, and distance probability distributions generated by the MD simulations. In a simple test of the transferability of the extended force field, the angle, dihedral, and distance probability distributions obtained from BD simulations of 56 three-residue peptides were compared to results from corresponding explicit-solvent MD simulations. In a more challenging test of the COFFDROP force field, it was used to simulate eight intrinsically disordered proteins and was shown to quite accurately reproduce the experimental hydrodynamic radii (Rhydro), provided that the favorable nonbonded interactions of the force field were uniformly scaled downward in magnitude. Overall, the results indicate that the COFFDROP force field is likely to find use in modeling the conformational behavior of intrinsically disordered proteins and multidomain proteins connected by flexible linkers.

  4. Parameterization of backbone flexibility in a coarse-grained force field for proteins (COFFDROP) derived from all-atom explicit-solvent molecular dynamics simulations of all possible two-residue peptides

    PubMed Central

    Frembgen-Kesner, Tamara; Andrews, Casey T.; Li, Shuxiang; Ngo, Nguyet Anh; Shubert, Scott A.; Jain, Aakash; Olayiwola, Oluwatoni; Weishaar, Mitch R.; Elcock, Adrian H.

    2015-01-01

    Recently, we reported the parameterization of a set of coarse-grained (CG) nonbonded potential functions, derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acid pairs, and designed for use in (implicit-solvent) Brownian dynamics (BD) simulations of proteins; this force field was named COFFDROP (COarse-grained Force Field for Dynamic Representations Of Proteins). Here, we describe the extension of COFFDROP to include bonded backbone terms derived from fitting to results of explicit-solvent MD simulations of all possible two-residue peptides containing the 20 standard amino acids, with histidine modeled in both its protonated and neutral forms. The iterative Boltzmann inversion (IBI) method was used to optimize new CG potential functions for backbone-related terms by attempting to reproduce angle, dihedral and distance probability distributions generated by the MD simulations. In a simple test of the transferability of the extended force field, the angle, dihedral and distance probability distributions obtained from BD simulations of 56 three-residue peptides were compared to results from corresponding explicit-solvent MD simulations. In a more challenging test of the COFFDROP force field, it was used to simulate eight intrinsically disordered proteins and was shown to quite accurately reproduce the experimental hydrodynamic radii (Rhydro), provided that the favorable nonbonded interactions of the force field were uniformly scaled downwards in magnitude. Overall, the results indicate that the COFFDROP force field is likely to find use in modeling the conformational behavior of intrinsically disordered proteins and multi-domain proteins connected by flexible linkers. PMID:26574429

  5. A virtual-system coupled multicanonical molecular dynamics simulation: principles and applications to free-energy landscape of protein-protein interaction with an all-atom model in explicit solvent.

    PubMed

    Higo, Junichi; Umezawa, Koji; Nakamura, Haruki

    2013-05-14

    We propose a novel generalized ensemble method, a virtual-system coupled multicanonical molecular dynamics (V-McMD), to enhance conformational sampling of biomolecules expressed by an all-atom model in an explicit solvent. In this method, a virtual system, of which physical quantities can be set arbitrarily, is coupled with the biomolecular system, which is the target to be studied. This method was applied to a system of an Endothelin-1 derivative, KR-CSH-ET1, known to form an antisymmetric homodimer at room temperature. V-McMD was performed starting from a configuration in which two KR-CSH-ET1 molecules were mutually distant in an explicit solvent. The lowest free-energy state (the most thermally stable state) at room temperature coincides with the experimentally determined native complex structure. This state was separated to other non-native minor clusters by a free-energy barrier, although the barrier disappeared with elevated temperature. V-McMD produced a canonical ensemble faster than a conventional McMD method.

  6. Explicit all-atom modeling of realistically sized ligand-capped nanocrystals.

    PubMed

    Kaushik, Ananth P; Clancy, Paulette

    2012-03-21

    We present a study of an explicit all-atom representation of nanocrystals of experimentally relevant sizes (up to 6 nm), "capped" with alkyl chain ligands, in vacuum. We employ all-atom molecular dynamics simulation methods in concert with a well-tested intermolecular potential model, MM3 (molecular mechanics 3), for the studies presented here. These studies include determining the preferred conformation of an isolated single nanocrystal (NC), pairs of isolated NCs, and (presaging studies of superlattice arrays) unit cells of NC superlattices. We observe that very small NCs (3 nm) behave differently in a superlattice as compared to larger NCs (6 nm and above) due to the conformations adopted by the capping ligands on the NC surface. Short ligands adopt a uniform distribution of orientational preferences, including some that lie against the face of the nanocrystal. In contrast, longer ligands prefer to interdigitate. We also study the effect of changing ligand length and ligand coverage on the NCs on the preferred ligand configurations. Since explicit all-atom modeling constrains the maximum system size that can be studied, we discuss issues related to coarse-graining the representation of the ligands, including a comparison of two commonly used coarse-grained models. We find that care has to be exercised in the choice of coarse-grained model. The data provided by these realistically sized ligand-capped NCs, determined using explicit all-atom models, should serve as a reference standard for future models of coarse-graining ligands using united atom models, especially for self-assembly processes.

  7. Constrained Unfolding of a Helical Peptide: Implicit versus Explicit Solvents.

    PubMed

    Bureau, Hailey R; Merz, Dale R; Hershkovits, Eli; Quirk, Stephen; Hernandez, Rigoberto

    2015-01-01

    Steered Molecular Dynamics (SMD) has been seen to provide the potential of mean force (PMF) along a peptide unfolding pathway effectively but at significant computational cost, particularly in all-atom solvents. Adaptive steered molecular dynamics (ASMD) has been seen to provide a significant computational advantage by limiting the spread of the trajectories in a staged approach. The contraction of the trajectories at the end of each stage can be performed by taking a structure whose nonequilibrium work is closest to the Jarzynski average (in naive ASMD) or by relaxing the trajectories under a no-work condition (in full-relaxation ASMD--namely, FR-ASMD). Both approaches have been used to determine the energetics and hydrogen-bonding structure along the pathway for unfolding of a benchmark peptide initially constrained as an α-helix in a water environment. The energetics are quite different to those in vacuum, but are found to be similar between implicit and explicit solvents. Surprisingly, the hydrogen-bonding pathways are also similar in the implicit and explicit solvents despite the fact that the solvent contact plays an important role in opening the helix.

  8. Design of lattice proteins with explicit solvent

    NASA Astrophysics Data System (ADS)

    Salvi, G.; Mölbert, S.; de Los Rios, P.

    2002-12-01

    Protein design is important to develop new drugs. As such, a knowledge of the correct model to use to design novel proteins is of the utmost importance. Here we show that a simple model where the solvent degrees of freedom are (semi)explicitly taken into account performs better than other existing models when compared to real data. Some consequences on the criteria to be used for protein design are discussed.

  9. Refinement of protein structures in explicit solvent.

    PubMed

    Linge, Jens P; Williams, Mark A; Spronk, Christian A E M; Bonvin, Alexandre M J J; Nilges, Michael

    2003-02-15

    We present a CPU efficient protocol for refinement of protein structures in a thin layer of explicit solvent and energy parameters with completely revised dihedral angle terms. Our approach is suitable for protein structures determined by theoretical (e.g., homology modeling or threading) or experimental methods (e.g., NMR). In contrast to other recently proposed refinement protocols, we put a strong emphasis on consistency with widely accepted covalent parameters and computational efficiency. We illustrate the method for NMR structure calculations of three proteins: interleukin-4, ubiquitin, and crambin. We show a comparison of their structure ensembles before and after refinement in water with and without a force field energy term for the dihedral angles; crambin was also refined in DMSO. Our results demonstrate the significant improvement of structure quality by a short refinement in a thin layer of solvent. Further, they show that a dihedral angle energy term in the force field is beneficial for structure calculation and refinement. We discuss the optimal weight for the energy constant for the backbone angle omega and include an extensive discussion of meaning and relevance of the calculated validation criteria, in particular root mean square Z scores for covalent parameters such as bond lengths.

  10. Connecting free energy surfaces in implicit and explicit solvent: an efficient method to compute conformational and solvation free energies.

    PubMed

    Deng, Nanjie; Zhang, Bin W; Levy, Ronald M

    2015-06-09

    The ability to accurately model solvent effects on free energy surfaces is important for understanding many biophysical processes including protein folding and misfolding, allosteric transitions, and protein–ligand binding. Although all-atom simulations in explicit solvent can provide an accurate model for biomolecules in solution, explicit solvent simulations are hampered by the slow equilibration on rugged landscapes containing multiple basins separated by barriers. In many cases, implicit solvent models can be used to significantly speed up the conformational sampling; however, implicit solvent simulations do not fully capture the effects of a molecular solvent, and this can lead to loss of accuracy in the estimated free energies. Here we introduce a new approach to compute free energy changes in which the molecular details of explicit solvent simulations are retained while also taking advantage of the speed of the implicit solvent simulations. In this approach, the slow equilibration in explicit solvent, due to the long waiting times before barrier crossing, is avoided by using a thermodynamic cycle which connects the free energy basins in implicit solvent and explicit solvent using a localized decoupling scheme. We test this method by computing conformational free energy differences and solvation free energies of the model system alanine dipeptide in water. The free energy changes between basins in explicit solvent calculated using fully explicit solvent paths agree with the corresponding free energy differences obtained using the implicit/explicit thermodynamic cycle to within 0.3 kcal/mol out of ∼3 kcal/mol at only ∼8% of the computational cost. We note that WHAM methods can be used to further improve the efficiency and accuracy of the implicit/explicit thermodynamic cycle.

  11. Solvated molecular dynamics of LiCN isomerization: All-atom argon solvent versus a generalized Langevin bath.

    PubMed

    Junginger, Andrej; Garcia-Muller, Pablo L; Borondo, F; Benito, R M; Hernandez, Rigoberto

    2016-01-14

    The reaction rate rises and falls with increasing density or friction when a molecule is activated by collisions with the solvent particles. This so-called Kramers turnover has recently been observed in the isomerization reaction of LiCN in an argon bath. In this paper, we demonstrate by direct comparison with those results that a reduced-dimensional (generalized) Langevin description gives rise to similar reaction dynamics as the corresponding (computationally expensive) full molecular dynamics calculations. We show that the density distributions within the Langevin description are in direct agreement with the full molecular dynamics results and that the turnover in the reaction rates is reproduced qualitatively and quantitatively at different temperatures.

  12. Bridging implicit and explicit solvent approaches for membrane electrostatics.

    PubMed Central

    Lin, Jung-Hsin; Baker, Nathan A; McCammon, J Andrew

    2002-01-01

    Conformations of a zwitterionic bilayer were sampled from a molecular dynamics simulation and their electrostatic properties analyzed by solution of the Poisson equation. These traditionally implicit electrostatic calculations were performed in the presence of varying amounts of explicit solvent to assess the magnitude of error introduced by a uniform dielectric description of water surrounding the bilayer. It was observed that membrane dipole potential calculations in the presence of explicit water were significantly different than wholly implicit solvent calculations with the calculated dipole potential converging to a reasonable value when four or more hydration layers were included explicitly. PMID:12202363

  13. Density relaxation and particle motion characteristics in a non-ionic deep eutectic solvent (acetamide + urea): time-resolved fluorescence measurements and all-atom molecular dynamics simulations.

    PubMed

    Das, Anuradha; Das, Suman; Biswas, Ranjit

    2015-01-21

    Temperature dependent relaxation dynamics, particle motion characteristics, and heterogeneity aspects of deep eutectic solvents (DESs) made of acetamide (CH3CONH2) and urea (NH2CONH2) have been investigated by employing time-resolved fluorescence measurements and all-atom molecular dynamics simulations. Three different compositions (f) for the mixture [fCH3CONH2 + (1 - f)NH2CONH2] have been studied in a temperature range of 328-353 K which is ∼120-145 K above the measured glass transition temperatures (∼207 K) of these DESs but much lower than the individual melting temperature of either of the constituents. Steady state fluorescence emission measurements using probe solutes with sharply different lifetimes do not indicate any dependence on excitation wavelength in these metastable molten systems. Time-resolved fluorescence anisotropy measurements reveal near-hydrodynamic coupling between medium viscosity and rotation of a dissolved dipolar solute. Stokes shift dynamics have been found to be too fast to be detected by the time-resolution (∼70 ps) employed, suggesting extremely rapid medium polarization relaxation. All-atom simulations reveal Gaussian distribution for particle displacements and van Hove correlations, and significant overlap between non-Gaussian (α2) and new non-Gaussian (γ) heterogeneity parameters. In addition, no stretched exponential relaxations have been detected in the simulated wavenumber dependent acetamide dynamic structure factors. All these results are in sharp contrast to earlier observations for ionic deep eutectics with acetamide [Guchhait et al., J. Chem. Phys. 140, 104514 (2014)] and suggest a fundamental difference in interaction and dynamics between ionic and non-ionic deep eutectic solvent systems.

  14. Density relaxation and particle motion characteristics in a non-ionic deep eutectic solvent (acetamide + urea): Time-resolved fluorescence measurements and all-atom molecular dynamics simulations

    SciTech Connect

    Das, Anuradha; Das, Suman; Biswas, Ranjit

    2015-01-21

    Temperature dependent relaxation dynamics, particle motion characteristics, and heterogeneity aspects of deep eutectic solvents (DESs) made of acetamide (CH{sub 3}CONH{sub 2}) and urea (NH{sub 2}CONH{sub 2}) have been investigated by employing time-resolved fluorescence measurements and all-atom molecular dynamics simulations. Three different compositions (f) for the mixture [fCH{sub 3}CONH{sub 2} + (1 − f)NH{sub 2}CONH{sub 2}] have been studied in a temperature range of 328-353 K which is ∼120-145 K above the measured glass transition temperatures (∼207 K) of these DESs but much lower than the individual melting temperature of either of the constituents. Steady state fluorescence emission measurements using probe solutes with sharply different lifetimes do not indicate any dependence on excitation wavelength in these metastable molten systems. Time-resolved fluorescence anisotropy measurements reveal near-hydrodynamic coupling between medium viscosity and rotation of a dissolved dipolar solute. Stokes shift dynamics have been found to be too fast to be detected by the time-resolution (∼70 ps) employed, suggesting extremely rapid medium polarization relaxation. All-atom simulations reveal Gaussian distribution for particle displacements and van Hove correlations, and significant overlap between non-Gaussian (α{sub 2}) and new non-Gaussian (γ) heterogeneity parameters. In addition, no stretched exponential relaxations have been detected in the simulated wavenumber dependent acetamide dynamic structure factors. All these results are in sharp contrast to earlier observations for ionic deep eutectics with acetamide [Guchhait et al., J. Chem. Phys. 140, 104514 (2014)] and suggest a fundamental difference in interaction and dynamics between ionic and non-ionic deep eutectic solvent systems.

  15. An explicit-solvent conformation search method using open software

    PubMed Central

    Gaalswyk, Kari

    2016-01-01

    Computer modeling is a popular tool to identify the most-probable conformers of a molecule. Although the solvent can have a large effect on the stability of a conformation, many popular conformational search methods are only capable of describing molecules in the gas phase or with an implicit solvent model. We have developed a work-flow for performing a conformation search on explicitly-solvated molecules using open source software. This method uses replica exchange molecular dynamics (REMD) to sample the conformational states of the molecule efficiently. Cluster analysis is used to identify the most probable conformations from the simulated trajectory. This work-flow was tested on drug molecules α-amanitin and cabergoline to illustrate its capabilities and effectiveness. The preferred conformations of these molecules in gas phase, implicit solvent, and explicit solvent are significantly different. PMID:27280078

  16. Conformation of a Lennard-Jones polymer in explicit solvent

    NASA Astrophysics Data System (ADS)

    Ye, Yuting; Taylor, Mark

    2012-04-01

    The conformation of a polymer chain is solution is coupled to the local structure of the surrounding solvent and can undergo large changes in response to variations in solvent density and temperature. The many-body effects of solvent on the structure of an n-mer chain can be formally mapped to an exact n-body solvation potential. These potentials map the chain-solvent system to a single chain, thereby dramatically reducing the computational complexity of the polymer chain-in-solvent problem. We have recently shown that a pair-decomposition of this n-body potential is valid for short Lennard-Jones (LJ) chains in explicit LJ solvent [1]. Here we use these short chain results to construct solvation potentials for long chains. We present results for the size and intramolecular structure of LJ chains up to length n=400 in LJ solvent at state points spanning the solvent phase diagram (including vapor, liquid, and super-critical regions). In comparison with simulation results for the corresponding full chain-in-solvent system, our solvation potential approach is found to be quantitatively accurate for a wide range of solvent conditions and chain lengths.[4pt] [1] M.P. Taylor and S.R. Adhikari, J. Chem. Phys. 135, 044903 (2011).

  17. Conformation of a Lennard-Jones polymer in explicit solvent

    NASA Astrophysics Data System (ADS)

    Ye, Yuting; Taylor, Mark

    2011-10-01

    The conformation of a polymer chain is solution is coupled to the local structure of the surrounding solvent and can undergo large changes in response to variations in solvent density and temperature. The many-body effects of solvent on the structure of an n-mer chain can be formally mapped to an exact n-body solvation potential. These potentials map the chain-solvent system to a single chain, thereby dramatically reducing the computational complexity of the polymer chain-in-solvent problem. We have recently shown that a pair-decomposition of this n-body potential is valid for short Lennard-Jones (LJ) chains in explicit LJ solvent [1]. Here we use these short chain results to construct solvation potentials for long chains. We present results for the size and intramolecular structure of LJ chains up to length n=400 in LJ solvent at state points spanning the solvent phase diagram (including vapor, liquid, and super-critical regions). In comparison with simulation results for the corresponding full chain-in-solvent system, our solvation potential approach is found to be quantitatively accurate for a wide range of solvent conditions and chain lengths.[4pt] [1] M.P. Taylor and S.R. Adhikari, J. Chem. Phys. 135, 044903 (2011).

  18. Identifying native-like protein structures with scoring functions based on all-atom ECEPP force fields, implicit solvent models and structure relaxation.

    PubMed

    Arnautova, Yelena A; Vorobjev, Yury N; Vila, Jorge A; Scheraga, Harold A

    2009-10-01

    Availability of energy functions which can discriminate native-like from non-native protein conformations is crucial for theoretical protein structure prediction and refinement of low-resolution protein models. This article reports the results of benchmark tests for scoring functions based on two all-atom ECEPP force fields, that is, ECEPP/3 and ECEPP05, and two implicit solvent models for a large set of protein decoys. The following three scoring functions are considered: (i) ECEPP05 plus a solvent-accessible surface area model with the parameters optimized with a set of protein decoys (ECEPP05/SA); (ii) ECEPP/3 plus the solvent-accessible surface area model of Ooi et al. (Proc Natl Acad Sci USA 1987;84:3086-3090) (ECEPP3/OONS); and (iii) ECEPP05 plus an implicit solvent model based on a solution of the Poisson equation with an optimized Fast Adaptive Multigrid Boundary Element (FAMBEpH) method (ECEPP05/FAMBEpH). Short Monte Carlo-with-Minimization (MCM) simulations, following local energy minimization, are used as a scoring method with ECEPP05/SA and ECEPP3/OONS potentials, whereas energy calculation is used with ECEPP05/FAMBEpH. The performance of each scoring function is evaluated by examining its ability to distinguish between native-like and non-native protein structures. The results of the tests show that the new ECEPP05/SA scoring function represents a significant improvement over the earlier ECEPP3/OONS version of the force field. Thus, it is able to rank native-like structures with C(alpha) root-mean-square-deviations below 3.5 A as lowest-energy conformations for 76% and within the top 10 for 87% of the proteins tested, compared with 69 and 80%, respectively, for ECEPP3/OONS. The use of the FAMBEpH solvation model, which provides a more accurate description of the protein-solvent interactions, improves the discriminative ability of the scoring function to 89%. All failed tests in which the native-like structures cannot be discriminated as those with low

  19. Explicit solvent models in protein pKa calculations.

    PubMed

    Gibas, C J; Subramaniam, S

    1996-07-01

    Continuum methods for calculation of protein electrostatics treat buried and ordered water molecules by one of two approximations; either the dielectric constant of regions containing ordered water molecules is equal to the bulk solvent dielectric constant, or it is equal to the protein dielectric constant though no fixed atoms are used to represent water molecules. A method for calculating the titration behavior of individual residues in proteins has been tested on models of hen egg white lysozyme containing various numbers of explicit water molecules. Water molecules were included based on hydrogen bonding, solvent accessibility, and/or proximity to titrating groups in the protein. Inclusion of water molecules significantly alters the calculated titration behavior of individual titrating sites, shifting calculated pKa values by up to 0.5 pH unit. Our results suggest that approximately one water molecule within hydrogen-bonding distance of each charged group should be included in protein electrostatics calculations.

  20. Electrostatic interactions in charged nanoslits within an explicit solvent theory.

    PubMed

    Buyukdagli, Sahin

    2015-11-18

    Within a dipolar Poisson-Boltzmann theory including electrostatic correlations, we consider the effect of explicit solvent structure on solvent and ion partition confined to charged nanopores. We develop a relaxation scheme for the solution of this highly non-linear integro-differential equation for the electrostatic potential. The scheme is an extension of the approach previously introduced for simple planes (Buyukdagli and Blossey 2014 J. Chem. Phys. 140 234903) to nanoslit geometry. We show that the reduced dielectric response of solvent molecules at the membrane walls gives rise to an electric field significantly stronger than the field of the classical Poisson-Boltzmann equation. This peculiarity associated with non-local electrostatic interactions results in turn in an interfacial counterion adsorption layer absent in continuum theories. The observation of this enhanced counterion affinity in the very close vicinity of the interface may have important impacts on nanofluidic transport through charged nanopores. Our results indicate the quantitative inaccuracy of solvent implicit nanofiltration theories in predicting the ionic selectivity of membrane nanopores.

  1. Electrostatic interactions in charged nanoslits within an explicit solvent theory

    NASA Astrophysics Data System (ADS)

    Buyukdagli, Sahin

    2015-11-01

    Within a dipolar Poisson-Boltzmann theory including electrostatic correlations, we consider the effect of explicit solvent structure on solvent and ion partition confined to charged nanopores. We develop a relaxation scheme for the solution of this highly non-linear integro-differential equation for the electrostatic potential. The scheme is an extension of the approach previously introduced for simple planes (Buyukdagli and Blossey 2014 J. Chem. Phys. 140 234903) to nanoslit geometry. We show that the reduced dielectric response of solvent molecules at the membrane walls gives rise to an electric field significantly stronger than the field of the classical Poisson-Boltzmann equation. This peculiarity associated with non-local electrostatic interactions results in turn in an interfacial counterion adsorption layer absent in continuum theories. The observation of this enhanced counterion affinity in the very close vicinity of the interface may have important impacts on nanofluidic transport through charged nanopores. Our results indicate the quantitative inaccuracy of solvent implicit nanofiltration theories in predicting the ionic selectivity of membrane nanopores.

  2. Solvent Reaction Field Potential inside an Uncharged Globular Protein: A Bridge between Implicit and Explicit Solvent Models?

    PubMed Central

    Baker, Nathan A.; McCammon, J. Andrew

    2008-01-01

    The solvent reaction field potential of an uncharged protein immersed in Simple Point Charge/Extended (SPC/E) explicit solvent was computed over a series of molecular dynamics trajectories, intotal 1560 ns of simulation time. A finite, positive potential of 13 to 24 kbTec−1 (where T = 300K), dependent on the geometry of the solvent-accessible surface, was observed inside the biomolecule. The primary contribution to this potential arose from a layer of positive charge density 1.0 Å from the solute surface, on average 0.008 ec/Å3, which we found to be the product of a highly ordered first solvation shell. Significant second solvation shell effects, including additional layers of charge density and a slight decrease in the short-range solvent-solvent interaction strength, were also observed. The impact of these findings on implicit solvent models was assessed by running similar explicit-solvent simulations on the fully charged protein system. When the energy due to the solvent reaction field in the uncharged system is accounted for, correlation between per-atom electrostatic energies for the explicit solvent model and a simple implicit (Poisson) calculation is 0.97, and correlation between per-atom energies for the explicit solvent model and a previously published, optimized Poisson model is 0.99. PMID:17949217

  3. Distinguishing native conformations of proteins from decoys with an effective free energy estimator based on the OPLS all-atom force field and the Surface Generalized Born solvent model.

    PubMed

    Felts, Anthony K; Gallicchio, Emilio; Wallqvist, Anders; Levy, Ronald M

    2002-08-01

    Protein decoy data sets provide a benchmark for testing scoring functions designed for fold recognition and protein homology modeling problems. It is commonly believed that statistical potentials based on reduced atomic models are better able to discriminate native-like from misfolded decoys than scoring functions based on more detailed molecular mechanics models. Recent benchmark tests on small data sets, however, suggest otherwise. In this work, we report the results of extensive decoy detection tests using an effective free energy function based on the OPLS all-atom (OPLS-AA) force field and the Surface Generalized Born (SGB) model for the solvent electrostatic effects. The OPLS-AA/SGB effective free energy is used as a scoring function to detect native protein folds among a total of 48,832 decoys for 32 different proteins from Park and Levitt's 4-state-reduced, Levitt's local-minima, Baker's ROSETTA all-atom, and Skolnick's decoy sets. Solvent electrostatic effects are included through the Surface Generalized Born (SGB) model. All structures are locally minimized without restraints. From an analysis of the individual energy components of the OPLS-AA/SGB energy function for the native and the best-ranked decoy, it is determined that a balance of the terms of the potential is responsible for the minimized energies that most successfully distinguish the native from the misfolded conformations. Different combinations of individual energy terms provide less discrimination than the total energy. The results are consistent with observations that all-atom molecular potentials coupled with intermediate level solvent dielectric models are competitive with knowledge-based potentials for decoy detection and protein modeling problems such as fold recognition and homology modeling.

  4. WAXSiS: a web server for the calculation of SAXS/WAXS curves based on explicit-solvent molecular dynamics

    PubMed Central

    Knight, Christopher J.; Hub, Jochen S.

    2015-01-01

    Small- and wide-angle X-ray scattering (SWAXS) has evolved into a powerful tool to study biological macromolecules in solution. The interpretation of SWAXS curves requires their accurate predictions from structural models. Such predictions are complicated by scattering contributions from the hydration layer and by effects from thermal fluctuations. Here, we describe the new web server WAXSiS (WAXS in solvent) that computes SWAXS curves based on explicit-solvent all-atom molecular dynamics (MD) simulations (http://waxsis.uni-goettingen.de/). The MD simulations provide a realistic model for both the hydration layer and the excluded solvent, thereby avoiding any solvent-related fitting parameters, while naturally accounting for thermal fluctuations. PMID:25855813

  5. An all-atom structure-based potential for proteins: bridging minimal models with all-atom empirical forcefields.

    PubMed

    Whitford, Paul C; Noel, Jeffrey K; Gosavi, Shachi; Schug, Alexander; Sanbonmatsu, Kevin Y; Onuchic, José N

    2009-05-01

    Protein dynamics take place on many time and length scales. Coarse-grained structure-based (Go) models utilize the funneled energy landscape theory of protein folding to provide an understanding of both long time and long length scale dynamics. All-atom empirical forcefields with explicit solvent can elucidate our understanding of short time dynamics with high energetic and structural resolution. Thus, structure-based models with atomic details included can be used to bridge our understanding between these two approaches. We report on the robustness of folding mechanisms in one such all-atom model. Results for the B domain of Protein A, the SH3 domain of C-Src Kinase, and Chymotrypsin Inhibitor 2 are reported. The interplay between side chain packing and backbone folding is explored. We also compare this model to a C(alpha) structure-based model and an all-atom empirical forcefield. Key findings include: (1) backbone collapse is accompanied by partial side chain packing in a cooperative transition and residual side chain packing occurs gradually with decreasing temperature, (2) folding mechanisms are robust to variations of the energetic parameters, (3) protein folding free-energy barriers can be manipulated through parametric modifications, (4) the global folding mechanisms in a C(alpha) model and the all-atom model agree, although differences can be attributed to energetic heterogeneity in the all-atom model, and (5) proline residues have significant effects on folding mechanisms, independent of isomerization effects. Because this structure-based model has atomic resolution, this work lays the foundation for future studies to probe the contributions of specific energetic factors on protein folding and function.

  6. An All-atom Structure-Based Potential for Proteins: Bridging Minimal Models with All-atom Empirical Forcefields

    PubMed Central

    Whitford, Paul C.; Noel, Jeffrey K.; Gosavi, Shachi; Schug, Alexander; Sanbonmatsu, Kevin Y.; Onuchic, José N.

    2012-01-01

    Protein dynamics take place on many time and length scales. Coarse-grained structure-based (Gō) models utilize the funneled energy landscape theory of protein folding to provide an understanding of both long time and long length scale dynamics. All-atom empirical forcefields with explicit solvent can elucidate our understanding of short time dynamics with high energetic and structural resolution. Thus, structure-based models with atomic details included can be used to bridge our understanding between these two approaches. We report on the robustness of folding mechanisms in one such all-atom model. Results for the B domain of Protein A, the SH3 domain of C-Src Kinase and Chymotrypsin Inhibitor 2 are reported. The interplay between side chain packing and backbone folding is explored. We also compare this model to a Cα structure-based model and an all-atom empirical forcefield. Key findings include 1) backbone collapse is accompanied by partial side chain packing in a cooperative transition and residual side chain packing occurs gradually with decreasing temperature 2) folding mechanisms are robust to variations of the energetic parameters 3) protein folding free energy barriers can be manipulated through parametric modifications 4) the global folding mechanisms in a Cα model and the all-atom model agree, although differences can be attributed to energetic heterogeneity in the all-atom model 5) proline residues have significant effects on folding mechanisms, independent of isomerization effects. Since this structure-based model has atomic resolution, this work lays the foundation for future studies to probe the contributions of specific energetic factors on protein folding and function. PMID:18837035

  7. Modeling Solvent Broadening on the Vibronic Spectra of a Series of Coumarin Dyes. From Implicit to Explicit Solvent Models.

    PubMed

    Cerezo, Javier; Avila Ferrer, Francisco J; Prampolini, Giacomo; Santoro, Fabrizio

    2015-12-08

    We present a protocol to estimate the solvent-induced broadening of electronic spectra based on a model that explicitly takes into account the environment embedding the solute. Starting from a classical approximation of the solvent contribution to the spectrum, the broadening arises from the spread of the excitation energies due to the fluctuation of the solvent coordinates, and it is represented as a Gaussian line shape that convolutes the vibronic spectrum of the solute. The latter is computed in harmonic approximation at room temperature with a time-dependent approach. The proposed protocol for the computation of spectral broadening exploits molecular dynamics (MD) simulations performed on the solute-solvent system, keeping the solute degrees of freedom frozen, followed by the computation of the excitation properties with a quantum mechanics/molecular mechanics (QM/MM) approach. The factors that might influence each step of the protocol are analyzed in detail, including the selection of the empirical force field (FF) adopted in the MD simulations and the QM/MM partition of the system to compute the excitation energies. The procedure is applied to a family of coumarin dyes, and the results are compared with experiments and with the predictions of a very recent work (Cerezo et al., Phys. Chem. Chem. Phys. 2015, 17, 11401-11411), where an implicit model was adopted for the solvent. The final spectra of the considered coumarins were obtained without including ad hoc phenomenological parameters and indicate that the broadenings computed with explicit and implicit models both follow the experimental trend, increasing as the polarity change from the initial to the final state increases. More in detail, the implicit model provides larger estimations of the broadening that are closer to the experimental evidence, while explicit models appear to better capture relative differences arising from different solvents or different solutes. Possible inaccuracies of the adopted

  8. Speed of Conformational Change: Comparing Explicit and Implicit Solvent Molecular Dynamics Simulations

    PubMed Central

    Anandakrishnan, Ramu; Drozdetski, Aleksander; Walker, Ross C.; Onufriev, Alexey V.

    2015-01-01

    Adequate sampling of conformation space remains challenging in atomistic simulations, especially if the solvent is treated explicitly. Implicit-solvent simulations can speed up conformational sampling significantly. We compare the speed of conformational sampling between two commonly used methods of each class: the explicit-solvent particle mesh Ewald (PME) with TIP3P water model and a popular generalized Born (GB) implicit-solvent model, as implemented in the AMBER package. We systematically investigate small (dihedral angle flips in a protein), large (nucleosome tail collapse and DNA unwrapping), and mixed (folding of a miniprotein) conformational changes, with nominal simulation times ranging from nanoseconds to microseconds depending on system size. The speedups in conformational sampling for GB relative to PME simulations, are highly system- and problem-dependent. Where the simulation temperatures for PME and GB are the same, the corresponding speedups are approximately onefold (small conformational changes), between ∼1- and ∼100-fold (large changes), and approximately sevenfold (mixed case). The effects of temperature on speedup and free-energy landscapes, which may differ substantially between the solvent models, are discussed in detail for the case of miniprotein folding. In addition to speeding up conformational sampling, due to algorithmic differences, the implicit solvent model can be computationally faster for small systems or slower for large systems, depending on the number of solute and solvent atoms. For the conformational changes considered here, the combined speedups are approximately twofold, ∼1- to 60-fold, and ∼50-fold, respectively, in the low solvent viscosity regime afforded by the implicit solvent. For all the systems studied, 1) conformational sampling speedup increases as Langevin collision frequency (effective viscosity) decreases; and 2) conformational sampling speedup is mainly due to reduction in solvent viscosity rather than

  9. Conformation of a flexible polymer in explicit solvent: Accurate solvation potentials for Lennard-Jones chains.

    PubMed

    Taylor, Mark P; Ye, Yuting; Adhikari, Shishir R

    2015-11-28

    The conformation of a polymer chain in solution is coupled to the local structure of the surrounding solvent and can undergo large changes in response to variations in solvent density and temperature. The many-body effects of solvent on the structure of an n-mer polymer chain can be formally mapped to an exact n-body solvation potential. Here, we use a pair decomposition of this n-body potential to construct a set of two-body potentials for a Lennard-Jones (LJ) polymer chain in explicit LJ solvent. The solvation potentials are built from numerically exact results for 5-mer chains in solvent combined with an approximate asymptotic expression for the solvation potential between sites that are distant along the chain backbone. These potentials map the many-body chain-in-solvent problem to a few-body single-chain problem and can be used to study a chain of arbitrary length, thereby dramatically reducing the computational complexity of the polymer chain-in-solvent problem. We have constructed solvation potentials at a large number of state points across the LJ solvent phase diagram including the vapor, liquid, and super-critical regions. We use these solvation potentials in single-chain Monte Carlo (MC) simulations with n ≤ 800 to determine the size, intramolecular structure, and scaling behavior of chains in solvent. To assess our results, we have carried out full chain-in-solvent MC simulations (with n ≤ 100) and find that our solvation potential approach is quantitatively accurate for a wide range of solvent conditions for these chain lengths.

  10. Flexibility and explicit solvent in molecular-dynamics-based docking of protein-glycosaminoglycan systems.

    PubMed

    Samsonov, Sergey A; Gehrcke, Jan-Philip; Pisabarro, M Teresa

    2014-02-24

    We present Dynamic Molecular Docking (DMD), a novel targeted molecular dynamics-based protocol developed to address ligand and receptor flexibility as well as the inclusion of explicit solvent in local molecular docking. A class of ligands for which docking performance especially benefits from overcoming these challenges is the glycosaminoglycans (GAGs). GAGs are periodic, highly flexible, and negatively charged polysaccharides playing an important role in the extracellular matrix via interaction with proteins such as growth factors and chemokines. The goal of our work has been to develop a proof of concept for an MD-based docking approach and to analyze its applicability for protein-GAG systems. DMD exploits the electrostatics-driven attraction of a ligand to its receptor, treats both as entirely flexible, and considers solvent explicitly. We show that DMD has high predictive significance for systems dominated by electrostatic attraction and demonstrate its capability to reliably identify the receptor residues contributing most to binding.

  11. Combining coarse-grained protein models with replica-exchange all-atom molecular dynamics.

    PubMed

    Wabik, Jacek; Kmiecik, Sebastian; Gront, Dominik; Kouza, Maksim; Koliński, Andrzej

    2013-05-10

    We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a model system of protein folding. After reconstructing atomistic details, conformations derived from the CABS simulation were subjected to replica-exchange molecular dynamics simulations with OPLS-AA and AMBER99sb force fields in explicit solvent. Such a combination accelerates system convergence several times in comparison with all-atom simulations starting from the extended chain conformation, demonstrated by the analysis of melting curves, the number of native-like conformations as a function of time and secondary structure propagation. The results strongly suggest that the proposed multiscale method could be an efficient and accurate tool for high-resolution studies of protein folding dynamics in larger systems.

  12. Interpretation of Solution X-Ray Scattering by Explicit-Solvent Molecular Dynamics

    PubMed Central

    Chen, Po-chia; Hub, Jochen S.

    2015-01-01

    Small- and wide-angle x-ray scattering (SWAXS) and molecular dynamics (MD) simulations are complementary approaches that probe conformational transitions of biomolecules in solution, even in a time-resolved manner. However, the structural interpretation of the scattering signals is challenging, while MD simulations frequently suffer from incomplete sampling or from a force-field bias. To combine the advantages of both techniques, we present a method that incorporates solution scattering data as a differentiable energetic restraint into explicit-solvent MD simulations, termed SWAXS-driven MD, with the aim to direct the simulation into conformations satisfying the experimental data. Because the calculations fully rely on explicit solvent, no fitting parameters associated with the solvation layer or excluded solvent are required, and the calculations remain valid at wide angles. The complementarity of SWAXS and MD is illustrated using three biological examples, namely a periplasmic binding protein, aspartate carbamoyltransferase, and a nuclear exportin. The examples suggest that SWAXS-driven MD is capable of refining structures against SWAXS data without foreknowledge of possible reaction paths. In turn, the SWAXS data accelerates conformational transitions in MD simulations and reduces the force-field bias. PMID:25992735

  13. Polymer brushes in explicit poor solvents studied using a new variant of the bond fluctuation model

    NASA Astrophysics Data System (ADS)

    Jentzsch, Christoph; Sommer, Jens-Uwe

    2014-09-01

    Using a variant of the Bond Fluctuation Model which improves its parallel efficiency in particular running on graphic cards we perform large scale simulations of polymer brushes in poor explicit solvent. Grafting density, solvent quality, and chain length are varied. Different morphological structures in particular octopus micelles are observed for low grafting densities. We reconsider the theoretical model for octopus micelles proposed by Williams using scaling arguments with the relevant scaling variable being σ/σc, and with the characteristic grafting density given by σc ˜ N-4/3. We find that octopus micelles only grow laterally, but not in height and we propose an extension of the model by assuming a cylindrical shape instead of a spherical geometry for the micelle-core. We show that the scaling variable σ/σc can be applied to master plots for the averaged height of the brush, the size of the micelles, and the number of chains per micelle. The exponents in the corresponding power law relations for the grafting density and chain length are in agreement with the model for flat cylindrical micelles. We also investigate the surface roughness and find that polymer brushes in explicit poor solvent at grafting densities higher than the stretching transition are flat and surface rippling can only be observed close to the stretching transition.

  14. Computing solvent-induced forces in the solvation approach called Semi Explicit Assembly

    NASA Astrophysics Data System (ADS)

    Brini, Emiliano; Hummel, Michelle H.; Coutsias, Evangelos A.; Fennell, Christopher J.; Dill, Ken A.

    2014-03-01

    Many biologically relevant processes (e.g. protein folding) are often too big and slow to be simulated by computer methods that model atomically detailed water. Faster physical models of water are needed. We have developed an approach called Semi Explicit Assembly (SEA) [C.J. Fennell, C.W. Kehoe, K.A. Dill, PNAS, 108, 3234 (2011)]. It is physical because it uses pre-simulations of explicit-solvent models, and it is fast because at runtime, we just combine the pre-simulated results in rapid computations. SEA has also now been proven physically accurate in two blind tests called SAMPL. Here, we describe the computation of solvation forces in SEA, so that this solvation procedure can be incorporated into standard molecular dynamics codes. We describe experimental tests.

  15. Hopping and diffusion of ultrasoft particles in cluster crystals in the explicit presence of a solvent

    NASA Astrophysics Data System (ADS)

    Montes-Saralegui, Marta; Nikoubashman, Arash; Kahl, Gerhard

    2013-05-01

    We have investigated diffusion and hopping processes in a cluster crystal formed from mesoscopic, ultrasoft particles. In contrast to previous contributions we have explicitly included in our investigations the microscopic solvent by using a simulation scheme that takes the induced hydrodynamic interactions into account as faithfully as possible. In our investigations we first focused on the processes of migration of the ultrasoft particles. By evaluating dynamical correlation functions we were able to demonstrate that the presence of the solvent does indeed have an important impact on the diffusion and hopping processes of the particles: this applies in particular to the diffusive behaviour, to the angular orientation of the jump events and to the spatial extents of these events. In a second set-up we have added non-cluster-forming ultrasoft particles to the system, investigating thus the impact of the solvent and that of the mutual interaction of the two species of ultrasoft particles on their respective dynamic behaviours. Our investigations clearly demonstrate, beside the expected significant role that the solvent plays in this set-up, that diffusion and the jump processes show distinct differences for the two particle species.

  16. Nonadiabatic dynamics of electron transfer in solution: Explicit and implicit solvent treatments that include multiple relaxation time scales

    SciTech Connect

    Schwerdtfeger, Christine A.; Soudackov, Alexander V.; Hammes-Schiffer, Sharon

    2014-01-21

    The development of efficient theoretical methods for describing electron transfer (ET) reactions in condensed phases is important for a variety of chemical and biological applications. Previously, dynamical dielectric continuum theory was used to derive Langevin equations for a single collective solvent coordinate describing ET in a polar solvent. In this theory, the parameters are directly related to the physical properties of the system and can be determined from experimental data or explicit molecular dynamics simulations. Herein, we combine these Langevin equations with surface hopping nonadiabatic dynamics methods to calculate the rate constants for thermal ET reactions in polar solvents for a wide range of electronic couplings and reaction free energies. Comparison of explicit and implicit solvent calculations illustrates that the mapping from explicit to implicit solvent models is valid even for solvents exhibiting complex relaxation behavior with multiple relaxation time scales and a short-time inertial response. The rate constants calculated for implicit solvent models with a single solvent relaxation time scale corresponding to water, acetonitrile, and methanol agree well with analytical theories in the Golden rule and solvent-controlled regimes, as well as in the intermediate regime. The implicit solvent models with two relaxation time scales are in qualitative agreement with the analytical theories but quantitatively overestimate the rate constants compared to these theories. Analysis of these simulations elucidates the importance of multiple relaxation time scales and the inertial component of the solvent response, as well as potential shortcomings of the analytical theories based on single time scale solvent relaxation models. This implicit solvent approach will enable the simulation of a wide range of ET reactions via the stochastic dynamics of a single collective solvent coordinate with parameters that are relevant to experimentally accessible

  17. Effects of solvent (effective medium versus explicit) on the structure of a protein (H3.1)

    NASA Astrophysics Data System (ADS)

    Pandey, Ras; Farmer, Barry

    2015-03-01

    Structure and dynamics of a histone (H3.1) are studied in the presence of effective medium and explicit solvent over a range of temperatures with coarse-grained Monte Carlo simulations. The protein is represented by a coarse-grained chain of residues whose interactions are described by knowledge-based residue-residue and hydropathy-index-based residue-solvent interactions. Each empty lattice site acts as a solvent in effective medium while a fraction of sites are occupied by mobile solvent constituents in explicit solvent medium. The presence of fluctuations with explicit solvent may affect the structure and dynamics of protein differently than that in effective solvent medium. Large scale simulations are performed to analyze the structure of the protein for a range of residue-solvent interactions and temperature, and a number of local and global physical quantities are analyzed. Differences due to type of solvent on the response of some of these quantities as a function of temperature will be presented.

  18. Explicit solvent effects on the visible absorption spectrum of a photosynthetic pigment: Chlorophyll-c 2 in methanol

    NASA Astrophysics Data System (ADS)

    Jaramillo, Paula; Coutinho, Kaline; Cabral, Benedito J. C.; Canuto, Sylvio

    2011-11-01

    The explicit solvent effects on the light absorption properties of a photosynthetic pigment are analyzed from a combined study using Monte Carlo simulation and quantum mechanical Density-Functional Theory calculations. The case considered is chlorophyll-c2 in methanol and excellent results are obtained for both position and intensities in the entire visible region. Explicit solvent molecules are essential for describing the absorption spectrum. Analysis is also made of the coordination of the Mg atom, the influence of solute-solvent hydrogen bonds, the existence and location of dark states for internal conversion mechanisms and the adequacy of the four-state model for classifying the transitions.

  19. Distinct conformational properties determined by implicit and explicit representation of protein-solvent interactions. An analytical and computer simulation study

    NASA Astrophysics Data System (ADS)

    Rocha, L. F. O.; Silva, I. R.; Caliri, A.

    2009-10-01

    In the protein folding problem, solvent-mediated forces are commonly represented by intra-chain pairwise contact energy. Although this approximation has proven to be useful in several circumstances, it is limited in some other aspects of the problem. Here we show that it is possible to achieve two models to represent the chain-solvent system, one of them with implicit and other with explicit solvent, such that both reproduce the same thermodynamic results. Firstly, lattice models treated by analytical methods, were used to show that the implicit and explicitly representation of solvent effects can be energetically equivalent only if local solvent properties are time and spatially invariant. Following, applying the same reasoning used for the lattice models, two inter-consistent Monte Carlo off-lattice models for implicit and explicit solvent are constructed, being that now in the latter the solvent properties are allowed to fluctuate. Then, it is shown that the chain configurational evolution as well as the globule equilibrium conformation are significantly distinct for implicit and explicit solvent systems. Actually, strongly contrasting with the implicit solvent version, the explicit solvent model predicts: (i) a malleable globule, in agreement with the estimated large protein-volume fluctuations; (ii) thermal conformational stability, resembling the conformational heat resistance of globular proteins, in which radii of gyration are practically insensitive to thermal effects over a relatively wide range of temperatures; and (iii) smaller radii of gyration at higher temperatures, indicating that the chain conformational entropy in the unfolded state is significantly smaller than that estimated from random coil configurations. Finally, we comment on the meaning of these results with respect to the understanding of the folding process.

  20. Convergence and sampling efficiency in replica exchange simulations of peptide folding in explicit solvent.

    PubMed

    Periole, Xavier; Mark, Alan E

    2007-01-07

    Replica exchange methods (REMs) are increasingly used to improve sampling in molecular dynamics (MD) simulations of biomolecular systems. However, despite having been shown to be very effective on model systems, the application of REM in complex systems such as for the simulation of protein and peptide folding in explicit solvent has not been objectively tested in detail. Here we present a comparison of conventional MD and temperature replica exchange MD (T-REMD) simulations of a beta-heptapeptide in explicit solvent. This system has previously been shown to undergo reversible folding on the time scales accessible to MD simulation and thus allows a direct one-to-one comparison of efficiency. The primary properties compared are the free energy of folding and the relative populations of different conformers as a function of temperature. It is found that to achieve a similar degree of precision T-REMD simulations starting from a random set of initial configurations were approximately an order of magnitude more computationally efficient than a single 800 ns conventional MD simulation for this system at the lowest temperature investigated (275 K). However, whereas it was found that T-REMD simulations are more than four times more efficient than multiple independent MD simulations at one temperature (300 K) the actual increase in conformation sampling was only twofold. The overall gain in efficiency using REMD resulted primarily from the ordering of different conformational states over temperature, as opposed to a large increase of conformational sampling. It is also shown that in this system exchanges are accepted primarily based on (random) fluctuations within the solvent and are not strongly correlated with the instantaneous peptide conformation raising questions in regard to the efficiency of T-REMD in larger systems.

  1. Multi-Million-Atom Molecular Dynamics Simulations of Polymer Nanoparticle Composites using Explicit Solvent Treatment

    NASA Astrophysics Data System (ADS)

    Deshmukh, Sanket; Kamath, Ganesh; Mancini, Derrick; Sankaranarayanan, Subramanian

    2014-03-01

    Poly(N-isopropylacrylamide) (PNIPAM) is a thermosensitive polymer that is well-known for its lower critical solution temperature (LCST) around 305K. Below the LCST, PNIPAM is soluble in water, and above this temperature, polymer chains collapse and transform into a globule-state. Our simulations of systems consisting of single polymer chains in presence of explicit water molecules (~ 50 K atoms) predicted the LCST of PNIPAM close to the observed experimental value of ~ 305 K. This study also suggested the importance of using an explicit water model in studying the coil-to-globule transition in thermo-sensitive polymers. In the current studies, we are carrying out MD simulations of composites of PNIPAM inorganic nanoparticles in the aqueous solution using an explicit solvent treatment. We study the effect of grafting density on the coil-to-globule transition of the PNIPAM brushes. We graft PNIPAM polymer chains consisting of 60 monomer units onto a gold nanoparticle with varying grafting densities. Studied system consisted of ~3 million atoms. All the simulations were carried out below (275K) and above (325K) the LCST of PNIPAM. Simulation trajectories are analyzed for structural and dynamical properties. In particular, we look at the morphology of the uncollapsed and collapsed structures, and relate this to observation in scattering measurements. Future work will expand this approach to studying the dynamics of agglomeration of such brush structures to form self-assembled nanocomposites.

  2. Oxidation induced decomposition of ethylene carbonate from DFT calculations--importance of explicitly treating surrounding solvent.

    PubMed

    Xing, Lidan; Borodin, Oleg

    2012-10-05

    The oxidation induced reactions of the common lithium battery electrolyte solvent ethylene carbonate (EC) have been investigated for EC(2) using density functional theory and for selected reaction paths using Møller-Plesset perturbation theory (MP4). The importance of explicitly treating at least one solvent molecule interacting with EC during oxidation (removal of an electron) on the EC oxidation potential and decomposition reactions was shown by comparing oxidation of EC and EC(2). Accuracy of DFT results was evaluated by comparing with MP4 and G4 values for oxidation of EC. The polarized continuum model (PCM) was used to implicitly include the rest of the surrounding solvent. The oxidation potentials of EC(2) and EC(4) were found to be significantly lower than the intrinsic oxidation potential of an isolated EC and also lower than the oxidation potential of EC-BF(4)(-). The exothermic proton abstraction from the ethylene group of EC by the carbonyl group of another EC was responsible for the decreased oxidative stability of EC(2) and EC(4) compared to EC. The most exothermic path with the smallest barrier for EC(2) oxidation yielded CO(2) and an ethanol radical cation. The reaction paths with the higher barrier yielded oligo(ethylene carbonate) suggesting a pathway for the experimentally observed poly(ethylene carbonate) formation of EC-based electrolytes at cathode surfaces.

  3. Finite-size effect on the charging free energy of protein in explicit solvent.

    PubMed

    Ekimoto, Toru; Matubayasi, Nobuyuki; Ikeguchi, Mitsunori

    2015-01-13

    The finite-size effect in periodic system is examined for the charging free energy of protein in explicit solvent over a variety of charged states. The key to the finite-size correction is the self-energy, which is defined as the interaction energy of the solute with its own periodic images and the neutralizing background. By employing the thermodynamic-integration method with systematically varied sizes of the unit cell of molecular dynamics (MD) simulations, we show for ubiquitin that the self-energy corrects the finite-size effect on the charging free energy within 1 kcal/mol at total charges of -5e, -1e, neutral, and +1e and within 5 kcal/mol even for a highly charged state with +8e. We then sought the additional correction from the solvation effect using the numerical solution to the Poisson equation of the protein with implicit solvent. This correction reduces the cell-size dependence of the charging free energy at +8e to 3 kcal/mol and is well expressed as the self-energy divided by the dielectric constant of solvent water.

  4. A comparison of implicit- and explicit-solvent simulations of self-assembly in block copolymer and solute systems

    NASA Astrophysics Data System (ADS)

    Spaeth, Justin R.; Kevrekidis, Ioannis G.; Panagiotopoulos, Athanassios Z.

    2011-04-01

    We have developed explicit- and implicit-solvent models for the flash nanoprecipitation process, which involves rapid coprecipitation of block copolymers and solutes by changing solvent quality. The explicit-solvent model uses the dissipative particle dynamics (DPD) method and the implicit-solvent model uses the Brownian dynamics (BD) method. Each of the two models was parameterized to match key properties of the diblock copolymer (specifically, critical micelle concentration, diffusion coefficient, polystyrene melt density, and polyethylene glycol radius of gyration) and the hydrophobic solute (aqueous solubility, diffusion coefficient, and solid density). The models were simulated in the limit of instantaneous mixing of solvent with antisolvent. Despite the significant differences in the potentials employed in the implicit- and explicit-solvent models, the polymer-stabilized nanoparticles formed in both sets of simulations are similar in size and structure; however, the dynamic evolution of the two simulations is quite different. Nanoparticles in the BD simulations have diffusion coefficients that follow Rouse behavior (D ∝ M-1), whereas those in the DPD simulations have diffusion coefficients that are close to the values predicted by the Stokes-Einstein relation (D ∝ R-1). As the nanoparticles become larger, the discrepancy between diffusion coefficients grows. As a consequence, BD simulations produce increasingly slower aggregation dynamics with respect to real time and result in an unphysical evolution of the nanoparticle size distribution. Surface area per polymer of the stable explicit-solvent nanoparticles agrees well with experimental values, whereas the implicit-solvent nanoparticles are stable when the surface area per particle is roughly two to four times larger. We conclude that implicit-solvent models may produce questionable results when simulating nonequilibrium processes in which hydrodynamics play a critical role.

  5. A comparison of implicit- and explicit-solvent simulations of self-assembly in block copolymer and solute systems.

    PubMed

    Spaeth, Justin R; Kevrekidis, Ioannis G; Panagiotopoulos, Athanassios Z

    2011-04-28

    We have developed explicit- and implicit-solvent models for the flash nanoprecipitation process, which involves rapid coprecipitation of block copolymers and solutes by changing solvent quality. The explicit-solvent model uses the dissipative particle dynamics (DPD) method and the implicit-solvent model uses the Brownian dynamics (BD) method. Each of the two models was parameterized to match key properties of the diblock copolymer (specifically, critical micelle concentration, diffusion coefficient, polystyrene melt density, and polyethylene glycol radius of gyration) and the hydrophobic solute (aqueous solubility, diffusion coefficient, and solid density). The models were simulated in the limit of instantaneous mixing of solvent with antisolvent. Despite the significant differences in the potentials employed in the implicit- and explicit-solvent models, the polymer-stabilized nanoparticles formed in both sets of simulations are similar in size and structure; however, the dynamic evolution of the two simulations is quite different. Nanoparticles in the BD simulations have diffusion coefficients that follow Rouse behavior (D ∝ M(-1)), whereas those in the DPD simulations have diffusion coefficients that are close to the values predicted by the Stokes-Einstein relation (D ∝ R(-1)). As the nanoparticles become larger, the discrepancy between diffusion coefficients grows. As a consequence, BD simulations produce increasingly slower aggregation dynamics with respect to real time and result in an unphysical evolution of the nanoparticle size distribution. Surface area per polymer of the stable explicit-solvent nanoparticles agrees well with experimental values, whereas the implicit-solvent nanoparticles are stable when the surface area per particle is roughly two to four times larger. We conclude that implicit-solvent models may produce questionable results when simulating nonequilibrium processes in which hydrodynamics play a critical role.

  6. Trypsin-Ligand Binding Free Energies from Explicit and Implicit Solvent Simulations with Polarizable Potential

    PubMed Central

    Jiao, Dian; Zhang, Jiajing; Duke, Robert E.; Li, Guohui; Ren, Pengyu

    2009-01-01

    We have calculated the binding free energies of a series of benzamidine-like inhibitors to trypsin with a polarizable force field using both explicit and implicit solvent approaches. Free energy perturbation has been performed for the ligands in bulk water and in protein complex with molecular dynamics simulations. The calculated binding free energies are well within the accuracy of experimental measurement and the direction of change is predicted correctly in call cases. We analyzed the molecular dipole moments of the ligands in gas, water and protein environments. Neither binding affinity nor ligand solvation free energy in bulk water shows much dependence on the molecular dipole moments of the ligands. Substitution of the aromatic or the charged group in the ligand results in considerable change in the solvation energy in bulk water and protein whereas the binding affinity varies insignificantly due to cancellation. The effect of chemical modification on ligand charge distribution is mostly local. Replacing benzene with diazine has minimal impact on the atomic multipoles at the amidinium group. We have also utilized an implicit solvent based end-state approach to evaluate the binding free energies of these inhibitors. In this approach, the polarizable multipole model combined with Poisson-Boltzmann/surface area (PMPB/SA) provides the electrostatic interaction energy and the polar solvation free energy. Overall the relative binding free energies obtained from the PMPB/SA model are in good agreement with the experimental data. PMID:19399779

  7. Increasing the sampling efficiency of protein conformational transition using velocity-scaling optimized hybrid explicit/implicit solvent REMD simulation

    SciTech Connect

    Yu, Yuqi; Wang, Jinan; Shao, Qiang E-mail: Jiye.Shi@ucb.com Zhu, Weiliang E-mail: Jiye.Shi@ucb.com; Shi, Jiye E-mail: Jiye.Shi@ucb.com

    2015-03-28

    The application of temperature replica exchange molecular dynamics (REMD) simulation on protein motion is limited by its huge requirement of computational resource, particularly when explicit solvent model is implemented. In the previous study, we developed a velocity-scaling optimized hybrid explicit/implicit solvent REMD method with the hope to reduce the temperature (replica) number on the premise of maintaining high sampling efficiency. In this study, we utilized this method to characterize and energetically identify the conformational transition pathway of a protein model, the N-terminal domain of calmodulin. In comparison to the standard explicit solvent REMD simulation, the hybrid REMD is much less computationally expensive but, meanwhile, gives accurate evaluation of the structural and thermodynamic properties of the conformational transition which are in well agreement with the standard REMD simulation. Therefore, the hybrid REMD could highly increase the computational efficiency and thus expand the application of REMD simulation to larger-size protein systems.

  8. Solute and solvent dynamics in confined equal-sized aqueous environments of charged and neutral reverse micelles: a combined dynamic fluorescence and all-atom molecular dynamics simulation study.

    PubMed

    Guchhait, Biswajit; Biswas, Ranjit; Ghorai, Pradip K

    2013-03-28

    Here a combined dynamic fluorescence and all-atom molecular dynamics simulation study of aqueous pool-size dependent solvation energy and rotational relaxations of a neutral dipolar solute, C153, trapped in AOT (charged) and IGPAL (neutral) reverse micelles (RMs) at 298 K, is described. RMs in simulations have been represented by a reduced model where SPC/E water molecules interact with a trapped C153 that possesses realistic charge distributions for both ground and excited states. In large aqueous pools, measured average solvation and rotation rates are smaller for the neutral RMs than those in charged ones. Interestingly, while the measured average solvation and rotation rates increase with pool size for the charged RMs, the average rotation rates for the neutral RMs exhibit a reverse dependence. Simulations have qualitatively reproduced this experimental trend and suggested interfacial location for the solute for all cases. The origin for the subnanosecond Stokes shift dynamics has been investigated and solute-interface interaction contribution quantified. Simulated layer-wise translational and rotational diffusions of water molecules re-examine the validity of the core-shell model and provide a resolution to a debate regarding the origin of the subnanosecond solvation component in dynamic Stokes shift measurements with aqueous RMs but not detected in ultrafast IR measurements.

  9. Computational scheme for pH-dependent binding free energy calculation with explicit solvent.

    PubMed

    Lee, Juyong; Miller, Benjamin T; Brooks, Bernard R

    2016-01-01

    We present a computational scheme to compute the pH-dependence of binding free energy with explicit solvent. Despite the importance of pH, the effect of pH has been generally neglected in binding free energy calculations because of a lack of accurate methods to model it. To address this limitation, we use a constant-pH methodology to obtain a true ensemble of multiple protonation states of a titratable system at a given pH and analyze the ensemble using the Bennett acceptance ratio (BAR) method. The constant pH method is based on the combination of enveloping distribution sampling (EDS) with the Hamiltonian replica exchange method (HREM), which yields an accurate semi-grand canonical ensemble of a titratable system. By considering the free energy change of constraining multiple protonation states to a single state or releasing a single protonation state to multiple states, the pH dependent binding free energy profile can be obtained. We perform benchmark simulations of a host-guest system: cucurbit[7]uril (CB[7]) and benzimidazole (BZ). BZ experiences a large pKa shift upon complex formation. The pH-dependent binding free energy profiles of the benchmark system are obtained with three different long-range interaction calculation schemes: a cutoff, the particle mesh Ewald (PME), and the isotropic periodic sum (IPS) method. Our scheme captures the pH-dependent behavior of binding free energy successfully. Absolute binding free energy values obtained with the PME and IPS methods are consistent, while cutoff method results are off by 2 kcal mol(-1) . We also discuss the characteristics of three long-range interaction calculation methods for constant-pH simulations.

  10. Energy landscape of all-atom protein-protein interactions revealed by multiscale enhanced sampling.

    PubMed

    Moritsugu, Kei; Terada, Tohru; Kidera, Akinori

    2014-10-01

    Protein-protein interactions are regulated by a subtle balance of complicated atomic interactions and solvation at the interface. To understand such an elusive phenomenon, it is necessary to thoroughly survey the large configurational space from the stable complex structure to the dissociated states using the all-atom model in explicit solvent and to delineate the energy landscape of protein-protein interactions. In this study, we carried out a multiscale enhanced sampling (MSES) simulation of the formation of a barnase-barstar complex, which is a protein complex characterized by an extraordinary tight and fast binding, to determine the energy landscape of atomistic protein-protein interactions. The MSES adopts a multicopy and multiscale scheme to enable for the enhanced sampling of the all-atom model of large proteins including explicit solvent. During the 100-ns MSES simulation of the barnase-barstar system, we observed the association-dissociation processes of the atomistic protein complex in solution several times, which contained not only the native complex structure but also fully non-native configurations. The sampled distributions suggest that a large variety of non-native states went downhill to the stable complex structure, like a fast folding on a funnel-like potential. This funnel landscape is attributed to dominant configurations in the early stage of the association process characterized by near-native orientations, which will accelerate the native inter-molecular interactions. These configurations are guided mostly by the shape complementarity between barnase and barstar, and lead to the fast formation of the final complex structure along the downhill energy landscape.

  11. Quantum Dynamics in an Explicit Solvent Environment: A Photochemical Bond Cleavage Treated with a Combined QD/MD Approach.

    PubMed

    Thallmair, Sebastian; Zauleck, Julius P P; de Vivie-Riedle, Regina

    2015-05-12

    In quantum chemistry methods to describe environmental effects on different levels of complexity are available in the common program packages. Electrostatic effects of a solvent for example can be included in an implicit or explicit way. For chemical reactions with large structural changes additional mechanical effects come into play. Their treatment within a quantum dynamical context is a major challenge, especially when excited states are involved. Recently, we introduced a method that realizes an implicit description. Here, we present an approach combining quantum dynamics and molecular dynamics. It explicitly incorporates the solvent environment, whereby the electrostatic as well as the dynamic effects are captured. This new method is demonstrated for the ultrafast photoinduced bond cleavage of diphenylmethylphosphonium ions (Ph2CH-PPh3(+)), a common precursor to generate reactive carbocations in solution.

  12. Explicit solvent simulations of the aqueous oxidation potential and reorganization energy for neutral molecules: gas phase, linear solvent response, and non-linear response contributions.

    PubMed

    Guerard, Jennifer J; Tentscher, Peter R; Seijo, Marianne; Samuel Arey, J

    2015-06-14

    First principles simulations were used to predict aqueous one-electron oxidation potentials (Eox) and associated half-cell reorganization energies (λaq) for aniline, phenol, methoxybenzene, imidazole, and dimethylsulfide. We employed quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations of the oxidized and reduced species in an explicit aqueous solvent, followed by EOM-IP-CCSD computations with effective fragment potentials for diabatic energy gaps of solvated clusters, and finally thermodynamic integration of the non-linear solvent response contribution using classical MD. A priori predicted Eox and λaq values exhibit mean absolute errors of 0.17 V and 0.06 eV, respectively, compared to experiment. We also disaggregate Eox into several well-defined free energy properties, including the gas phase adiabatic free energy of ionization (7.73 to 8.82 eV), the solvent-induced shift in the free energy of ionization due to linear solvent response (-2.01 to -2.73 eV), and the contribution from non-linear solvent response (-0.07 to -0.14 eV). The linear solvent response component is further apportioned into contributions from the solvent-induced shift in vertical ionization energy of the reduced species (ΔVIEaq) and the solvent-induced shift in negative vertical electron affinity of the ionized species (ΔNVEAaq). The simulated ΔVIEaq and ΔNVEAaq are found to contribute the principal sources of uncertainty in computational estimates of Eox and λaq. Trends in the magnitudes of disaggregated solvation properties are found to correlate with trends in structural and electronic features of the solute. Finally, conflicting approaches for evaluating the aqueous reorganization energy are contrasted and discussed, and concluding recommendations are given.

  13. COMPUTER SIMULATIONS WITH EXPLICIT SOLVENT: Recent Progress in the Thermodynamic Decomposition of Free Energies and in Modeling Electrostatic Effects

    NASA Astrophysics Data System (ADS)

    Levy, Ronald M.; Gallicchio, Emilio

    1998-10-01

    This review focuses on recent progress in two areas in which computer simulations with explicit solvent are being applied: the thermodynamic decomposition of free energies, and modeling electrostatic effects. The computationally intensive nature of these simulations has been an obstacle to the systematic study of many problems in solvation thermodynamics, such as the decomposition of solvation and ligand binding free energies into component enthalpies and entropies. With the revolution in computer power continuing, these problems are ripe for study but require the judicious choice of algorithms and approximations. We provide a critical evaluation of several numerical approaches to the thermodynamic decomposition of free energies and summarize applications in the current literature. Progress in computer simulations with explicit solvent of charge perturbations in biomolecules was slow in the early 1990s because of the widespread use of truncated Coulomb potentials in these simulations, among other factors. Development of the sophisticated technology described in this review to handle the long-range electrostatic interactions has increased the predictive power of these simulations to the point where comparisons between explicit and continuum solvent models can reveal differences that have their true physical origin in the inherent molecularity of the surrounding medium.

  14. Free-energy landscape of intrinsically disordered proteins investigated by all-atom multicanonical molecular dynamics.

    PubMed

    Higo, Junichi; Umezawa, Koji

    2014-01-01

    We introduce computational studies on intrinsically disordered proteins (IDPs). Especially, we present our multicanonical molecular dynamics (McMD) simulations of two IDP-partner systems: NRSF-mSin3 and pKID-KIX. McMD is one of enhanced conformational sampling methods useful for conformational sampling of biomolecular systems. IDP adopts a specific tertiary structure upon binding to its partner molecule, although it is unstructured in the unbound state (i.e. the free state). This IDP-specific property is called "coupled folding and binding". The McMD simulation treats the biomolecules with an all-atom model immersed in an explicit solvent. In the initial configuration of simulation, IDP and its partner molecules are set to be distant from each other, and the IDP conformation is disordered. The computationally obtained free-energy landscape for coupled folding and binding has shown that native- and non-native-complex clusters distribute complicatedly in the conformational space. The all-atom simulation suggests that both of induced-folding and population-selection are coupled complicatedly in the coupled folding and binding. Further analyses have exemplified that the conformational fluctuations (dynamical flexibility) in the bound and unbound states are essentially important to characterize IDP functioning.

  15. Infrared and vibrational CD spectra of partially solvated alpha-helices: DFT-based simulations with explicit solvent.

    PubMed

    Turner, David R; Kubelka, Jan

    2007-02-22

    Theoretical simulations are used to investigate the effects of aqueous solvent on the vibrational spectra of model alpha-helices, which are only partly exposed to solvent to mimic alpha-helices in proteins. Infrared absorption (IR) and vibrational circular dichroism (VCD) amide I' spectra for 15-amide alanine alpha-helices are simulated using density functional theory (DFT) calculations combined with the property transfer method. The solvent is modeled by explicit water molecules hydrogen bonded to the solvated amide groups. Simulated spectra for two partially solvated model alpha-helices, one corresponding to a more exposed and the other to a more buried structure, are compared to the fully solvated and unsolvated (gas phase) simulations. The dependence of the amide I spectra on the orientation of the partially solvated helix with respect to the solvent and effects of solvation on the amide I' of 13C isotopically substituted alpha-helices are also investigated. The partial exposure to solvent causes significant broadening of the amide I' bands due to differences in the vibrational frequencies of the explicitly solvated and unsolvated amide groups. The different degree of partial solvation is reflected primarily in the frequency shifts of the unsolvated (buried) amide group vibrations. Depending on which side of the alpha-helix is exposed to solvent, the simulated IR band-shapes exhibit significant changes, from broad and relatively featureless to distinctly split into two maxima. The simulated amide I' VCD band-shapes for the partially solvated alpha-helices parallel the broadening of the IR and exhibit more sign variation, but generally preserve the sign pattern characteristic of the alpha-helical structures and are much less dependent on the alpha-helix orientation with respect to the solvent. The simulated amide I' IR spectra for the model peptides with explicitly hydrogen-bonded water are consistent with the experimental data for small alpha-helical proteins

  16. Density functional study on a light-harvesting carotenoid-porphyrin-C60 molecular triad in explicit solvent

    NASA Astrophysics Data System (ADS)

    Diaz, Carlos; Baruah, Tunna; Zope, Rajendra

    We investigate the effect of solvent on the electronic structure of a biomimetic molecular triad that shows photoinduced charge transfer in laboratory. The supramolecular triad contains three different units - C60, porphyrin, and beta-carotenoid. We have performed classical molecular dynamics simulation of the triad surrounded by 15000 water molecules using NAMD for 20 nanoseconds. Subsequently, we performed an all-electron density functional calculations (DFT) using large basis sets on the 50 snap-shots taken from the molecular dynamics simulation. The solvent effects in the DFT calculations are treated using both the explicit water molecules as well as using the point charge representation of water. The excitation energies and absorption spectra show that the polar solvent induces significant changes in the electronic structure of the triad.

  17. Solvent effects on IR and VCD spectra of helical peptides: DFT-based static spectral simulations with explicit water.

    PubMed

    Kubelka, Jan; Huang, Rong; Keiderling, Timothy A

    2005-04-28

    Simulations of IR and VCD spectra are carried out for model alpha-helical, 3(10)-helical, and 3(1)-helical (polyProII-like) oligopeptides, with up to 21 amide groups, and including explicit consideration of effects of directly hydrogen-bonded solvent (water). Parameters used were obtained from ab initio density functional theory (DFT) computations of force field, atomic polar and axial tensors for oligopeptides of 5 to 7 amides, whose structures were constrained in (phi,psi) to target the secondary structure type but otherwise fully optimized. By comparison with experimental data as well as with calculations for identical but isolated (gas phase) peptides, the computed effects of an inner shell of aqueous solvent on the vibrational spectra of helical oligopeptides are illustrated. The interaction with solvent causes significant frequency shifts of the amide bands, but only minor changes in the characteristic IR intensity distributions and splittings and the VCD band shapes. Better agreement with experimental band shapes is achieved for the alpha-helical amide I' (N-deuterated) VCD by inclusion of explicit solvent in the calculations. Some improvements are also observed in theoretical VCD predictions for 13C labeled alpha-helical peptides when solvated models are used. However, the qualitative isotopic splitting patterns are preserved and just shifted in frequency due to consistent, solvent independent interamide coupling constants. The critical match of experiment and theory for relative positions of transitions in peptides with specifically separated 13C=O labels, including and neglecting solvent, confirms the stability of the coupling interactions. Despite these solvation effects, the calculated VCD band shape of the amide I mode is shown to be a reliable conformational probe, since it remains basically insensitive to frequency shifts caused by environment. Thus theoretical VCD simulations, even vacuum calculations, are shown to provide useful spectral

  18. TIGER2 with solvent energy averaging (TIGER2A): An accelerated sampling method for large molecular systems with explicit representation of solvent

    NASA Astrophysics Data System (ADS)

    Li, Xianfeng; Snyder, James A.; Stuart, Steven J.; Latour, Robert A.

    2015-10-01

    The recently developed "temperature intervals with global exchange of replicas" (TIGER2) accelerated sampling method is found to have inaccuracies when applied to systems with explicit solvation. This inaccuracy is due to the energy fluctuations of the solvent, which cause the sampling method to be less sensitive to the energy fluctuations of the solute. In the present work, the problem of the TIGER2 method is addressed in detail and a modification to the sampling method is introduced to correct this problem. The modified method is called "TIGER2 with solvent energy averaging," or TIGER2A. This new method overcomes the sampling problem with the TIGER2 algorithm and is able to closely approximate Boltzmann-weighted sampling of molecular systems with explicit solvation. The difference in performance between the TIGER2 and TIGER2A methods is demonstrated by comparing them against analytical results for simple one-dimensional models, against replica exchange molecular dynamics (REMD) simulations for sampling the conformation of alanine dipeptide and the folding behavior of (AAQAA)3 peptide in aqueous solution, and by comparing their performance in sampling the behavior of hen egg-white lysozyme in aqueous solution. The new TIGER2A method solves the problem caused by solvent energy fluctuations in TIGER2 while maintaining the two important characteristics of TIGER2, i.e., (1) using multiple replicas sampled at different temperature levels to help systems efficiently escape from local potential energy minima and (2) enabling the number of replicas used for a simulation to be independent of the size of the molecular system, thus providing an accelerated sampling method that can be used to efficiently sample systems considered too large for the application of conventional temperature REMD.

  19. Theory and simulation of explicit solvent effects on protein folding in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    England, Jeremy L.

    The aim of this work is to develop theoretical tools for understanding what happens to water that is confined in amphipathic cavities, and for testing the consequences of this understanding for protein folding in vitro and in vivo. We begin in the first chapter with a brief review of the theoretical and simulation literature on the hydrophobic effect and the aqueous solvation of charged species that also puts forward a simple theoretical framework within which various solvation phenomena reported in past studies may be unified. Subsequently, in the second chapter we also review past computational and theoretical work on the specific question of how chaperonin complexes assist the folding of their substrates. With the context set, we turn in Chapter 3 to the case of an open system with water trapped between hydrophobic plates that experiences a uniform electric field normal to and between the plates. Classic bulk theory of electrostriction in polarizable fluids tells us that the electric field should cause an increase in local water density as it rises, yet some simulations have suggested the opposite. We present a mean-field Potts model we have developed to explain this discrepancy, and show how such a simple, coarse-grained lattice description can capture the fundamental consequences of the fact that external electric fields can frustrate the hydrogen bond network in confined water. Chapter 4 continues to pursue the issue of solvent evacuation between hydrophobic plates, but focuses on the impact of chemical denaturants on hydrophobic effects using molecular dynamics simulations of hydrophobic dewetting. We find that while urea and guanidinium have similar qualitative effects at the bulk level, they seem to differ in the microscopic mechanism by which they denature proteins, although both inhibit the onset of dewetting. Lastly, Chapters 5 and 6 examine the potential importance of solvent-mediated forces to protein folding in vivo. Chapter 5 develops a Landau

  20. DFTr optimization and DFTr-MD studies of glucose, ten explicit water molecules enclosed by an implicit solvent, COSMO

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DFTr optimization studies are carried out on alpha/beta-glucose surrounded by ten explicit water molecules and the glucose/water super-molecule completely enclosed by an implicit solvation model, COSMO. Twenty one starting configurations of the explicit waters were first optimized empirically with t...

  1. Interplay among tertiary contacts, secondary structure formation and side-chain packing in the protein folding mechanism: all-atom representation study of protein L.

    PubMed

    Clementi, Cecilia; García, Angel E; Onuchic, José N

    2003-02-21

    Experimental and theoretical results suggest that, since proteins are energetically minimally frustrated, the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble and on-pathway intermediate states in protein folding. Although the central role of native state topology in determining the folding mechanism is thought to be a quite general result-at least for small two-state folding proteins-there are remarkable exceptions. Recent experimental findings have shown that topology alone cannot always determine the folding mechanism, and demonstrated that the balance between topology and energetics is very delicate. This balance seems to be particularly critical in proteins with a highly symmetrical native structure, such as proteins L and G, which have similar native structure topology but fold by different mechanisms. Simplified, C(alpha)-atom only protein models have shown not be sufficient to differentiate these mechanisms. An all-atom Gō model provides a valuable intermediate model between structurally simplified protein representations and all-atom protein simulations with explicit/implicit solvent descriptions. We present here a detailed study of an all-atom Gō-like representation of protein L, in close comparison with the experimental results and with the results obtained from a simple C(alpha)-atom representation of the same protein. We also perform simulations for protein G, where we obtain a folding mechanism in which the protein symmetry is broken exactly in the opposite way to protein L as has been observed experimentally. A detailed analysis for protein L also shows that the role of specific residues is correctly and quantitatively reproduced by the all-atom Gō model over almost the entire protein.

  2. DFT-based simulations of IR amide I' spectra for a small protein in solution. Comparison of explicit and empirical solvent models.

    PubMed

    Grahnen, Johan A; Amunson, Krista E; Kubelka, Jan

    2010-10-14

    Infrared (IR) amide I' spectra are widely used for investigations of the structural properties of proteins in aqueous solution. For analysis of the experimental data, it is necessary to separate the spectral features due to the backbone conformation from those arising from other factors, in particular the interaction with solvent. We investigate the effects of solvation on amide I' spectra for a small 40-residue helix-turn-helix protein by theoretical simulations based on density functional theory (DFT). The vibrational force fields and intensity parameters for the protein amide backbone are constructed by transfer from smaller heptaamide fragments; the side chains are neglected in the DFT calculations. Solvent is modeled at two different levels: first as explicit water hydrogen bonded to the surface amide groups, treated at the same DFT level, and, second, using the electrostatic map approach combined with molecular dynamics (MD) simulation. Motional narrowing of the spectral band shapes due to averaging over the fast solvent fluctuation is introduced by use of the time-averaging approximation (TAA). The simulations are compared with the experimental amide I', including two (13)C isotopically edited spectra, corrected for the side-chain signals. Both solvent models are consistent with the asymmetric experimental band shape, which arises from the differential solvation of the amide backbone. However, the effects of (13)C isotopic labeling are best captured by the gas-phase calculations. The limitations of the solvent models and implications for the theoretical simulations of protein amide vibrational spectra are discussed.

  3. Effect of interaction with coesite silica on the conformation of Cecropin P1 using explicit solvent molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Wu, Xiaoyu; Chang, Hector; Mello, Charlene; Nagarajan, Ramanathan; Narsimhan, Ganesan

    2013-01-01

    Explicit solvent molecular dynamics (MD) simulation was carried out for the antimicrobial peptides (i) Cecropin P1 and C-terminus cysteine modified Cecropin P1 (Cecropin P1 C) in solution, (ii) Cecropin P1 and Cecropin P1 C adsorbed onto coesite -Si - O - and Si - O - H surfaces, and (iii) Cecropin P1 C tethered to coesite -Si - O - surface with either (PEO)3 or (PEO)6 linker. Low energy structures for Cecropin P1 and Cecropin P1 C in solution consists of two regions of high α helix probability with a sharp bend, consistent with the available structures of other antimicrobial peptides. The structure of Cecropin P1 C at low ionic strength of 0.02 M exhibits two regions of high α helix probability (residues AKKLEN and EGI) whereas at higher ionic strength of 0.12 M, the molecule was more compact and had three regions of higher α helix probability (residues TAKKLENSA, ISE, and AIQG) with an increase in α helical content from 15.6% to 18.7% as a result of shielding of electrostatic interactions. In the presence of Cecropin P1 C in the vicinity of -Si - O - surface, there is a shift in the location of two peaks in H - O - H density profile to larger distances (2.95 Å and 7.38 Å compared to 2.82 Å and 4.88 Å in the absence of peptide) with attenuated peak intensity. This attenuation is found to be more pronounced for the first peak. H-bond density profile in the vicinity of -Si - O - surface exhibited a single peak in the presence of Cecropin P1 C (at 2.9 Å) which was only slightly different from the profile in the absence of polypeptide (2.82 Å) thus indicating that Cecropin P1 C is not able to break the H-bond formed by the silica surface. The α helix probability for different residues of adsorbed Cecropin P1 C on -Si - O - surface is not significantly different from that of Cecropin P1 C in solution at low ionic strength of 0.02 M whereas there is a decrease in the probability in the second (residues ISE) and third (residues AIQG) α helical regions at

  4. Combined QM/MM Molecular Dynamics Study on a Condensed-Phase SN2 Reaction at Nitrogen:  The Effect of Explicitly Including Solvent Polarization.

    PubMed

    Geerke, Daan P; Thiel, Stephan; Thiel, Walter; van Gunsteren, Wilfred F

    2007-07-01

    In a previous combined QM/MM molecular dynamics (MD) study from our laboratory on the identity SN2 reaction between a chloride anion and an amino chloride in liquid dimethyl ether (DME), an increase in the free energy activation barrier was observed in the condensed phase when compared to the gas-phase activation energy. Here we reproduce these findings, but when comparing the condensed-phase potential of mean force (PMF) with the free energy profile in the gas phase (obtained from Monte Carlo simulations), we observe a smaller solvent effect on the activation barrier of the reaction. In a next step, we introduce an explicit description of electronic polarization in the MM (solvent) part of the system. A polarizable force field for liquid DME was developed based on the charge-on-spring (COS) model, which was calibrated to reproduce thermodynamic properties of the nonpolarizable model in classical MD simulations. The COS model was implemented into the MNDO/GROMOS interface in a special version of the QM/MM software ChemShell, which was used to investigate the effect of solvent polarization on the free energy profile of the reaction under study. A higher activation barrier was obtained using the polarizable solvent model than with the nonpolarizable force field, due to a better solvation of and a stronger polarization of solvent molecules around the separate reactants. The obtained PMFs were subjected to an energy-entropy decomposition of the relative solvation free energies of the reactant complex along the reaction coordinate, to investigate in a quantitative manner whether the solvent (polarization) effects are mainly due to favorable QM-MM (energetic) interactions.

  5. All-atom models of the membrane-spanning domain of HIV-1 gp41 from metadynamics.

    PubMed

    Gangupomu, Vamshi K; Abrams, Cameron F

    2010-11-17

    The 27-residue membrane-spanning domain (MSD) of the HIV-1 glycoprotein gp41 bears conserved sequence elements crucial to the biological function of the virus, in particular a conserved GXXXG motif and a midspan arginine. However, structure-based explanations for the roles of these and other MSD features remain unclear. Using molecular dynamics and metadynamics calculations of an all-atom, explicit solvent, and membrane-anchored model, we study the conformational variability of the HIV-1 gp41 MSD. We find that the MSD peptide assumes a stable tilted α-helical conformation in the membrane. However, when the side chain of the midspan Arg (694) "snorkels" to the outer leaflet of the viral membrane, the MSD assumes a metastable conformation where the highly-conserved N-terminal core (between Lys(681) and Arg(694) and containing the GXXXG motif) unfolds. In contrast, when the Arg(694) side chain snorkels to the inner leaflet, the MSD peptide assumes a metastable conformation consistent with experimental observations where the peptide kinks at Phe(697) to facilitate Arg(694) snorkeling. Both of these models suggest specific ways that gp41 may destabilize viral membrane, priming the virus for fusion with a target cell.

  6. An All-Atom Force Field for Tertiary Structure Prediction of Helical Proteins

    PubMed Central

    Herges, T.; Wenzel, W.

    2004-01-01

    We have developed an all-atom free-energy force field (PFF01) for protein tertiary structure prediction. PFF01 is based on physical interactions and was parameterized using experimental structures of a family of proteins believed to span a wide variety of possible folds. It contains empirical, although sequence-independent terms for hydrogen bonding. Its solvent-accessible surface area solvent model was first fit to transfer energies of small peptides. The parameters of the solvent model were then further optimized to stabilize the native structure of a single protein, the autonomously folding villin headpiece, against competing low-energy decoys. Here we validate the force field for five nonhomologous helical proteins with 20–60 amino acids. For each protein, decoys with 2–3 Å backbone root mean-square deviation and correct experimental Cβ–Cβ distance constraints emerge as those with the lowest energy. PMID:15507688

  7. All-atom/coarse-grained hybrid predictions of distribution coefficients in SAMPL5

    NASA Astrophysics Data System (ADS)

    Genheden, Samuel; Essex, Jonathan W.

    2016-11-01

    We present blind predictions submitted to the SAMPL5 challenge on calculating distribution coefficients. The predictions were based on estimating the solvation free energies in water and cyclohexane of the 53 compounds in the challenge. These free energies were computed using alchemical free energy simulations based on a hybrid all-atom/coarse-grained model. The compounds were treated with the general Amber force field, whereas the solvent molecules were treated with the Elba coarse-grained model. Considering the simplicity of the solvent model and that we approximate the distribution coefficient with the partition coefficient of the neutral species, the predictions are of good accuracy. The correlation coefficient, R is 0.64, 82 % of the predictions have the correct sign and the mean absolute deviation is 1.8 log units. This is on a par with or better than the other simulation-based predictions in the challenge. We present an analysis of the deviations to experiments and compare the predictions to another submission that used all-atom solvent.

  8. All-atom/coarse-grained hybrid predictions of distribution coefficients in SAMPL5.

    PubMed

    Genheden, Samuel; Essex, Jonathan W

    2016-11-01

    We present blind predictions submitted to the SAMPL5 challenge on calculating distribution coefficients. The predictions were based on estimating the solvation free energies in water and cyclohexane of the 53 compounds in the challenge. These free energies were computed using alchemical free energy simulations based on a hybrid all-atom/coarse-grained model. The compounds were treated with the general Amber force field, whereas the solvent molecules were treated with the Elba coarse-grained model. Considering the simplicity of the solvent model and that we approximate the distribution coefficient with the partition coefficient of the neutral species, the predictions are of good accuracy. The correlation coefficient, R is 0.64, 82 % of the predictions have the correct sign and the mean absolute deviation is 1.8 log units. This is on a par with or better than the other simulation-based predictions in the challenge. We present an analysis of the deviations to experiments and compare the predictions to another submission that used all-atom solvent.

  9. Coarse-grained explicit solvent simulation of the translational and rotational diffusion of a spherical particle in a polymer solution

    NASA Astrophysics Data System (ADS)

    Pryamitsyn, Victor; Ganesan, Venkat

    We use an extension of DPD model to address the dynamical properties of a colloid particle in an unentangled semi-dilute polymer solution. Solvent and monomers are represented as DPD particles.The colloid particle is represented as a larger DPD particle with the rotational degrees of freedom and tangential component of the dissipative and random DPD interactions with the solvent and monomers. This allows us to model a finite slip length boundary condition at the particle fluid interface and study translational Dt and rotational Dr diffusivities of a spherical particle. For zero polymer concentration our results agree with the Stokes-Einstein (SE) theory. Fore dilute and semi-dilute polymer solutions we have found that polymer dynamic follow the Zimm model in a dilute regime and the Rouse model at high polymer concentration. For particles smaller than the polymer Rg observed Dt is much high than SE prediction for R >Rg SE prediction recovers. We have found that increase of Dr relative to SE is rather correlated to the R/Rg ratio than R/ξ, where ξ is the thickness of a depletion shell around the particle. Dr is very sensitive to the slip length at the particle fluid interface and insensitive to R/Rg.

  10. Contribution of explicit solvent effects to the binding affinity of small-molecule inhibitors in blood coagulation factor serine proteases.

    PubMed

    Abel, Robert; Salam, Noeris K; Shelley, John; Farid, Ramy; Friesner, Richard A; Sherman, Woody

    2011-06-06

    The prevention of blood coagulation is important in treating thromboembolic disorders, and several serine proteases involved in the coagulation cascade have been classified as pharmaceutically relevant. Whereas structure-based drug design has contributed to the development of some serine protease inhibitors, traditional computational methods have not been able to fully describe structure-activity relationships (SAR). Here, we study the SAR for a number of serine proteases by using a method that calculates the thermodynamic properties (enthalpy and entropy) of the water that solvates the active site. We show that the displacement of water from specific subpockets (such as S1-4 and the ester binding pocket) of the active site by the ligand can govern potency, especially for cases in which small chemical changes (i.e., a methyl group or halogen) result in a substantial increase in potency. Furthermore, we describe how relative binding free energies can be estimated by combining the water displacement energy with complementary terms from an implicit solvent molecular mechanics description binding.

  11. Conformational Properties of Sodium Polystyrenesulfonate in Water: Insights from a Coarse-Grained Model with Explicit Solvent.

    PubMed

    Mantha, Sriteja; Yethiraj, Arun

    2015-08-27

    Polymer solutions present a significant computational challenge because chemical realism on small length scales can be important, but the polymer molecules are very large. In polyelectrolyte solutions, there is often the additional complexity that the molecules consist of hydrophobic and charged groups, which makes an accurate treatment of the solvent, water, crucial. One route to achieve this balance is through coarse-grained models where several atoms on a monomer are grouped into one interaction site. In this work, we develop a coarse grained (CG) model for sodium polystyrenesulfonate (NaPSS) in water using a methodology consistent with the MARTINI coarse-graining philosophy, where four heavy atoms are grouped into one CG site. We consider two models for water: polarizable MARTINI (POL) and big multipole water (BMW). In each case, interaction parameters for the polymer sites are obtained by matching the potential of mean force between two monomers to results of atomistic simulations. The force field based on the POL water provides a more reasonable description of polymer properties than that based on the BMW water. We study the properties of single chains using the POL force field. Fully sulfonated chains are rodlike (i.e., the root-mean-square radius of gyration, Rg, scales linearly with degree of polymerization, N). When the fraction of sulfonation, f, is 0.25 or less, the chain collapses into a cylindrical globule. For f = 0.5, pearl-necklace conformations are observed when every second monomer is sulfonated. The lifetime of a counterion around a polymer is on the order of 100 ps, suggesting that there is no counterion condensation. The model is computationally feasible and should allow one to study the effect of local chemistry on the properties of polymers in aqueous solution.

  12. Explicit treatment of active-site waters enhances quantum mechanical/implicit solvent scoring: Inhibition of CDK2 by new pyrazolo[1,5-a]pyrimidines.

    PubMed

    Hylsová, Michaela; Carbain, Benoit; Fanfrlík, Jindřich; Musilová, Lenka; Haldar, Susanta; Köprülüoğlu, Cemal; Ajani, Haresh; Brahmkshatriya, Pathik S; Jorda, Radek; Kryštof, Vladimír; Hobza, Pavel; Echalier, Aude; Paruch, Kamil; Lepšík, Martin

    2017-01-27

    We present comprehensive testing of solvent representation in quantum mechanics (QM)-based scoring of protein-ligand affinities. To this aim, we prepared 21 new inhibitors of cyclin-dependent kinase 2 (CDK2) with the pyrazolo[1,5-a]pyrimidine core, whose activities spanned three orders of magnitude. The crystal structure of a potent inhibitor bound to the active CDK2/cyclin A complex revealed that the biphenyl substituent at position 5 of the pyrazolo[1,5-a]pyrimidine scaffold was located in a previously unexplored pocket and that six water molecules resided in the active site. Using molecular dynamics, protein-ligand interactions and active-site water H-bond networks as well as thermodynamics were probed. Thereafter, all the inhibitors were scored by the QM approach utilizing the COSMO implicit solvent model. Such a standard treatment failed to produce a correlation with the experiment (R(2) = 0.49). However, the addition of the active-site waters resulted in significant improvement (R(2) = 0.68). The activities of the compounds could thus be interpreted by taking into account their specific noncovalent interactions with CDK2 and the active-site waters. In summary, using a combination of several experimental and theoretical approaches we demonstrate that the inclusion of explicit solvent effects enhance QM/COSMO scoring to produce a reliable structure-activity relationship with physical insights. More generally, this approach is envisioned to contribute to increased accuracy of the computational design of novel inhibitors.

  13. Non-equilibrium reaction and relaxation dynamics in a strongly interacting explicit solvent: F + CD3CN treated with a parallel multi-state EVB model

    NASA Astrophysics Data System (ADS)

    Glowacki, David R.; Orr-Ewing, Andrew J.; Harvey, Jeremy N.

    2015-07-01

    We describe a parallelized linear-scaling computational framework developed to implement arbitrarily large multi-state empirical valence bond (MS-EVB) calculations within CHARMM and TINKER. Forces are obtained using the Hellmann-Feynman relationship, giving continuous gradients, and good energy conservation. Utilizing multi-dimensional Gaussian coupling elements fit to explicitly correlated coupled cluster theory, we built a 64-state MS-EVB model designed to study the F + CD3CN → DF + CD2CN reaction in CD3CN solvent (recently reported in Dunning et al. [Science 347(6221), 530 (2015)]). This approach allows us to build a reactive potential energy surface whose balanced accuracy and efficiency considerably surpass what we could achieve otherwise. We ran molecular dynamics simulations to examine a range of observables which follow in the wake of the reactive event: energy deposition in the nascent reaction products, vibrational relaxation rates of excited DF in CD3CN solvent, equilibrium power spectra of DF in CD3CN, and time dependent spectral shifts associated with relaxation of the nascent DF. Many of our results are in good agreement with time-resolved experimental observations, providing evidence for the accuracy of our MS-EVB framework in treating both the solute and solute/solvent interactions. The simulations provide additional insight into the dynamics at sub-picosecond time scales that are difficult to resolve experimentally. In particular, the simulations show that (immediately following deuterium abstraction) the nascent DF finds itself in a non-equilibrium regime in two different respects: (1) it is highly vibrationally excited, with ˜23 kcal mol-1 localized in the stretch and (2) its post-reaction solvation environment, in which it is not yet hydrogen-bonded to CD3CN solvent molecules, is intermediate between the non-interacting gas-phase limit and the solution-phase equilibrium limit. Vibrational relaxation of the nascent DF results in a spectral

  14. Non-equilibrium reaction and relaxation dynamics in a strongly interacting explicit solvent: F + CD{sub 3}CN treated with a parallel multi-state EVB model

    SciTech Connect

    Glowacki, David R.; Orr-Ewing, Andrew J.; Harvey, Jeremy N.

    2015-07-28

    We describe a parallelized linear-scaling computational framework developed to implement arbitrarily large multi-state empirical valence bond (MS-EVB) calculations within CHARMM and TINKER. Forces are obtained using the Hellmann-Feynman relationship, giving continuous gradients, and good energy conservation. Utilizing multi-dimensional Gaussian coupling elements fit to explicitly correlated coupled cluster theory, we built a 64-state MS-EVB model designed to study the F + CD{sub 3}CN → DF + CD{sub 2}CN reaction in CD{sub 3}CN solvent (recently reported in Dunning et al. [Science 347(6221), 530 (2015)]). This approach allows us to build a reactive potential energy surface whose balanced accuracy and efficiency considerably surpass what we could achieve otherwise. We ran molecular dynamics simulations to examine a range of observables which follow in the wake of the reactive event: energy deposition in the nascent reaction products, vibrational relaxation rates of excited DF in CD{sub 3}CN solvent, equilibrium power spectra of DF in CD{sub 3}CN, and time dependent spectral shifts associated with relaxation of the nascent DF. Many of our results are in good agreement with time-resolved experimental observations, providing evidence for the accuracy of our MS-EVB framework in treating both the solute and solute/solvent interactions. The simulations provide additional insight into the dynamics at sub-picosecond time scales that are difficult to resolve experimentally. In particular, the simulations show that (immediately following deuterium abstraction) the nascent DF finds itself in a non-equilibrium regime in two different respects: (1) it is highly vibrationally excited, with ∼23 kcal mol{sup −1} localized in the stretch and (2) its post-reaction solvation environment, in which it is not yet hydrogen-bonded to CD{sub 3}CN solvent molecules, is intermediate between the non-interacting gas-phase limit and the solution-phase equilibrium limit. Vibrational

  15. Probing the Huntingtin 1-17 membrane anchor on a phospholipid bilayer by using all-atom simulations.

    PubMed

    Côté, Sébastien; Binette, Vincent; Salnikov, Evgeniy S; Bechinger, Burkhard; Mousseau, Normand

    2015-03-10

    Mislocalization and aggregation of the huntingtin protein are related to Huntington's disease. Its first exon-more specifically the first 17 amino acids (Htt17)-is crucial for the physiological and pathological functions of huntingtin. It regulates huntingtin's activity through posttranslational modifications and serves as an anchor to membrane-containing organelles of the cell. Recently, structure and orientation of the Htt17 membrane anchor were determined using a combined solution and solid-state NMR approach. This prompted us to refine this model by investigating the dynamics and thermodynamics of this membrane anchor on a POPC bilayer using all-atom, explicit solvent molecular dynamics and Hamiltonian replica exchange. Our simulations are combined with various experimental measurements to generate a high-resolution atomistic model for the huntingtin Htt17 membrane anchor on a POPC bilayer. More precisely, we observe that the single α-helix structure is more stable in the phospholipid membrane than the NMR model obtained in the presence of dodecylphosphocholine detergent micelles. The resulting Htt17 monomer has its hydrophobic plane oriented parallel to the bilayer surface. Our results further unveil the key residues interacting with the membrane in terms of hydrogen bonds, salt-bridges, and nonpolar contributions. We also observe that Htt17 equilibrates at a well-defined insertion depth and that it perturbs the physical properties-order parameter, thickness, and area per lipid-of the bilayer in a manner that could favor its dimerization. Overall, our observations reinforce and refine the NMR measurements on the Htt17 membrane anchor segment of huntingtin that is of fundamental importance to its biological functions.

  16. All-atom contact model for understanding protein dynamics from crystallographic B-factors.

    PubMed

    Li, Da-Wei; Brüschweiler, Rafael

    2009-04-22

    An all-atom local contact model is described that can be used to predict protein motions underlying isotropic crystallographic B-factors. It uses a mean-field approximation to represent the motion of an atom in a harmonic potential generated by the surrounding atoms resting at their equilibrium positions. Based on a 400-ns molecular dynamics simulation of ubiquitin in explicit water, it is found that each surrounding atom stiffens the spring constant by a term that on average scales exponentially with the interatomic distance. This model combines features of the local density model by Halle and the local contact model by Zhang and Brüschweiler. When applied to a nonredundant set of 98 ultra-high resolution protein structures, an average correlation coefficient of 0.75 is obtained for all atoms. The systematic inclusion of crystal contact contributions and fraying effects is found to enhance the performance substantially. Because the computational cost of the local contact model scales linearly with the number of protein atoms, it is applicable to proteins of any size for the prediction of B-factors of both backbone and side-chain atoms. The model performs as well as or better than several other models tested, such as rigid-body motional models, the local density model, and various forms of the elastic network model. It is concluded that at the currently achievable level of accuracy, collective intramolecular motions are not essential for the interpretation of B-factors.

  17. A simple and transferable all-atom/coarse-grained hybrid model to study membrane processes.

    PubMed

    Genheden, Samuel; Essex, Jonathan W

    2015-10-13

    We present an efficient all-atom/coarse-grained hybrid model and apply it to membrane processes. This model is an extension of the all-atom/ELBA model applied previously to processes in water. Here, we improve the efficiency of the model by implementing a multiple-time step integrator that allows the atoms and the coarse-grained beads to be propagated at different timesteps. Furthermore, we fine-tune the interaction between the atoms and the coarse-grained beads by computing the potential of mean force of amino acid side chain analogs along the membrane normal and comparing to atomistic simulations. The model was independently validated on the calculation of small-molecule partition coefficients. Finally, we apply the model to membrane peptides. We studied the tilt angle of the Walp23 and Kalp23 helices in two different model membranes and the stability of the glycophorin A dimer. The model is efficient, accurate, and straightforward to use, as it does not require any extra interaction particles, layers of atomistic solvent molecules or tabulated potentials, thus offering a novel, simple approach to study membrane processes.

  18. Low molecular weight oligomers of amyloid peptides display β-barrel conformations: A replica exchange molecular dynamics study in explicit solvent

    NASA Astrophysics Data System (ADS)

    De Simone, Alfonso; Derreumaux, Philippe

    2010-04-01

    The self-assembly of proteins and peptides into amyloid fibrils is connected to over 40 pathological conditions including neurodegenerative diseases and systemic amyloidosis. Diffusible, low molecular weight protein and peptide oligomers that form in the early steps of aggregation appear to be the harmful cytotoxic species in the molecular etiology of these diseases. So far, the structural characterization of these oligomers has remained elusive owing to their transient and dynamic features. We here address, by means of full atomistic replica exchange molecular dynamics simulations, the energy landscape of heptamers of the amyloidogenic peptide NHVTLSQ from the beta-2 microglobulin protein. The simulations totaling 5 μs show that low molecular weight oligomers in explicit solvent consist of β-barrels in equilibrium with amorphous states and fibril-like assemblies. The results, also accounting for the influence of the pH on the conformational properties, provide a strong evidence of the formation of transient β-barrel assemblies in the early aggregation steps of amyloid-forming systems. Our findings are discussed in terms of oligomers cytotoxicity.

  19. Low molecular weight oligomers of amyloid peptides display beta-barrel conformations: a replica exchange molecular dynamics study in explicit solvent.

    PubMed

    De Simone, Alfonso; Derreumaux, Philippe

    2010-04-28

    The self-assembly of proteins and peptides into amyloid fibrils is connected to over 40 pathological conditions including neurodegenerative diseases and systemic amyloidosis. Diffusible, low molecular weight protein and peptide oligomers that form in the early steps of aggregation appear to be the harmful cytotoxic species in the molecular etiology of these diseases. So far, the structural characterization of these oligomers has remained elusive owing to their transient and dynamic features. We here address, by means of full atomistic replica exchange molecular dynamics simulations, the energy landscape of heptamers of the amyloidogenic peptide NHVTLSQ from the beta-2 microglobulin protein. The simulations totaling 5 micros show that low molecular weight oligomers in explicit solvent consist of beta-barrels in equilibrium with amorphous states and fibril-like assemblies. The results, also accounting for the influence of the pH on the conformational properties, provide a strong evidence of the formation of transient beta-barrel assemblies in the early aggregation steps of amyloid-forming systems. Our findings are discussed in terms of oligomers cytotoxicity.

  20. Structural Dynamics of Thrombin-Binding DNA Aptamer d(GGTTGGTGTGGTTGG) Quadruplex DNA Studied by Large-Scale Explicit Solvent Simulations.

    PubMed

    Reshetnikov, Roman; Golovin, Andrey; Spiridonova, Vera; Kopylov, Alexei; Šponer, Jiří

    2010-10-12

    The thrombin-binding aptamer (15-TBA) is a 15-mer DNA oligonucleotide with sequence d(GGTTGGTGTGGTTGG). 15-TBA folds into a quadruplex DNA (G-DNA) structure with two planar G-quartets connected by three single-stranded loops. The arrangement of the 15-TBA-thrombin complex is unclear, particularly with respect to the precise 15-TBA residues that interact with the thrombin structure. Our present understanding suggests either the 15-TBA single stranded loops containing sequential thymidines (TT) or alternatively a single-stranded loop, containing a guanine flanked by 2 thymidines (TGT), physically associates with thrombin protein. In the present study, the explicit solvent molecular dynamics (MD) simulation method was utilized to further analyze the 15-TBA-thrombin three-dimensional structure. Functional annotation of the loop residues was made with long simulations in the parmbsc0 force field. In total, the elapsed time of simulations carried out in this study exceeds 12 microseconds, substantially surpassing previous G-DNA simulation reports. Our simulations suggest that the TGT-loop function is to stabilize the structure of the aptamer, while the TT-loops participate in direct binding to thrombin. The findings of the present report advance our understanding of the molecular structure of the 15-TBA-thrombin structure further enabling the construction of biosensors for aptamer bases and the development of anticoagulant agents.

  1. The SAMPL5 host-guest challenge: computing binding free energies and enthalpies from explicit solvent simulations by the attach-pull-release (APR) method

    NASA Astrophysics Data System (ADS)

    Yin, Jian; Henriksen, Niel M.; Slochower, David R.; Gilson, Michael K.

    2017-01-01

    The absolute binding free energies and binding enthalpies of twelve host-guest systems in the SAMPL5 blind challenge were computed using our attach-pull-release (APR) approach. This method has previously shown good correlations between experimental and calculated binding data in retrospective studies of cucurbit[7]uril (CB7) and β-cyclodextrin (βCD) systems. In the present work, the computed binding free energies for host octa acid (OA or OAH) and tetra-endo-methyl octa-acid (TEMOA or OAMe) with guests are in good agreement with prospective experimental data, with a coefficient of determination (R2) of 0.8 and root-mean-squared error of 1.7 kcal/mol using the TIP3P water model. The binding enthalpy calculations achieve moderate correlations, with R2 of 0.5 and RMSE of 2.5 kcal/mol, for TIP3P water. Calculations using the newly developed OPC water model also show good performance. Furthermore, the present calculations semi-quantitatively capture the experimental trend of enthalpy-entropy compensation observed, and successfully predict guests with the strongest and weakest binding affinity. The most populated binding poses of all twelve systems, based on clustering analysis of 750 ns molecular dynamics (MD) trajectories, were extracted and analyzed. Computational methods using MD simulations and explicit solvent models in a rigorous statistical thermodynamic framework, like APR, can generate reasonable predictions of binding thermodynamics. Especially with continuing improvement in simulation force fields, such methods hold the promise of making substantial contributions to hit identification and lead optimization in the drug discovery process.

  2. Large-scale analysis of 48 DNA and 48 RNA tetranucleotides studied by 1 μs explicit-solvent molecular dynamics simulations

    PubMed Central

    Schrodt, Michael V.; Andrews, Casey T.

    2016-01-01

    An understanding of how the conformational behavior of single-stranded DNAs and RNAs depend on sequence is likely to be important for attempts to rationalize the thermodynamics of nucleic acid folding. In an attempt to further our understanding of such sequence dependences we report here the results of 192 (1 μs) explicit-solvent molecular dynamics (MD) simulations of 48 DNA and 48 RNA tetranucleotide sequences performed using recently reported modifications to the AMBER force field. Each tetranucleotide was simulated starting from two different conformations – a fully natively-stacked, and a completely unstacked conformation – and populations of the various possible base stacking arrangements were analyzed. The simulations indicate that, for both DNA and RNA, the populations of fully natively stacked conformations increase linearly with increasing numbers of purines in the sequence, while the conformational entropies, computed by two complementary methods, decrease. Despite the comparatively short simulation times, the computed free energies of stacking of the 16 possible combinations of bases in the middle of the sequences are found to be in good correspondence with values reported recently from simulations of dinucleoside monophosphates using the same force field. Finally, consistent with recent reports from other groups, non-native stacking interactions, i.e. between bases that are not adjacent in sequence, are shown to be a recurring feature of the simulations; in particular, stacking interactions of bases in a i:i+2 relationship are shown to occur significantly more frequently when the intervening base is a pyrimidine. Given that the high prevalence of non-native stacking interactions is thought to be unrealistic, it appears that further parameterization work will be required before accurate conformational descriptions of single-stranded nucleic acids can be obtained with current force fields. PMID:26580891

  3. Predicting Partition Coefficients with a Simple All-Atom/Coarse-Grained Hybrid Model.

    PubMed

    Genheden, Samuel

    2016-01-12

    The solvation free energy is an essential quantity in force field development and in numerous applications. Here, we present the estimation of solvation free energies in polar (water, hexanol, octanol, and nonanol) and in apolar (hexane, octane, and nonane) media. The estimates are produced using molecular dynamics simulations employing a simple all-atom/coarse-grained hybrid model (AA/ELBA) and are therefore very efficient. More than 150 solutes were taken from the Minnesota solvation database and represent small, organic molecules. The mean absolute deviation for the different solvents ranges between 2.0 and 4.1 kJ/mol, and the correlation coefficient ranges between 0.78 and 0.99, indicating that the predictions are accurate. Outliers are identified, and potential avenues for improvements are discussed. Furthermore, partition coefficients between water and the organic solvents were estimated, and the percentage of the predictions that has the correct sign ranges between 74% (for octane) and 92% (for octanol and hexanol). Finally, membrane/water partition coefficients are replaced with hexane/water and octanol/water partition coefficients, and the latter is found to be as accurate as the expensive membrane calculations, indicating a wider application area.

  4. Multiscale approach for the construction of equilibrated all-atom models of a poly(ethylene glycol)-based hydrogel.

    PubMed

    Li, Xianfeng; Murthy, N Sanjeeva; Becker, Matthew L; Latour, Robert A

    2016-06-24

    A multiscale modeling approach is presented for the efficient construction of an equilibrated all-atom model of a cross-linked poly(ethylene glycol) (PEG)-based hydrogel using the all-atom polymer consistent force field (PCFF). The final equilibrated all-atom model was built with a systematic simulation toolset consisting of three consecutive parts: (1) building a global cross-linked PEG-chain network at experimentally determined cross-link density using an on-lattice Monte Carlo method based on the bond fluctuation model, (2) recovering the local molecular structure of the network by transitioning from the lattice model to an off-lattice coarse-grained (CG) model parameterized from PCFF, followed by equilibration using high performance molecular dynamics methods, and (3) recovering the atomistic structure of the network by reverse mapping from the equilibrated CG structure, hydrating the structure with explicitly represented water, followed by final equilibration using PCFF parameterization. The developed three-stage modeling approach has application to a wide range of other complex macromolecular hydrogel systems, including the integration of peptide, protein, and/or drug molecules as side-chains within the hydrogel network for the incorporation of bioactivity for tissue engineering, regenerative medicine, and drug delivery applications.

  5. All-atom molecular dynamics simulation of a photosystem i/detergent complex.

    PubMed

    Harris, Bradley J; Cheng, Xiaolin; Frymier, Paul

    2014-10-09

    All-atom molecular dynamics (MD) simulation was used to investigate the solution structure and dynamics of the photosynthetic pigment-protein complex photosystem I (PSI) from Thermosynechococcus elongatus embedded in a toroidal belt of n-dodecyl-β-d-maltoside (DDM) detergent. Evaluation of root-mean-square deviations (RMSDs) relative to the known crystal structure show that the protein complex surrounded by DDM molecules is stable during the 200 ns simulation time, and root-mean-square fluctuation (RMSF) analysis indicates that regions of high local mobility correspond to solvent-exposed regions such as turns in the transmembrane α-helices and flexible loops on the stromal and lumenal faces. Comparing the protein-detergent complex to a pure detergent micelle, the detergent surrounding the PSI trimer is found to be less densely packed but with more ordered detergent tails, contrary to what is seen in most lipid bilayer models. We also investigated any functional implications for the observed conformational dynamics and protein-detergent interactions, discovering interesting structural changes in the psaL subunits associated with maintaining the trimeric structure of the protein. Importantly, we find that the docking of soluble electron mediators such as cytochrome c6 and ferredoxin to PSI is not significantly impacted by the solubilization of PSI in detergent.

  6. A hybrid all-atom/coarse grain model for multiscale simulations of DNA.

    PubMed

    Machado, Matías Rodrigo; Dans, Pablo Daniel; Pantano, Sergio

    2011-10-28

    Hybrid simulations of molecular systems, which combine all-atom (AA) with simplified (or coarse grain, CG) representations, propose an advantageous alternative to gain atomistic details on relevant regions while getting profit from the speedup of treating a bigger part of the system at the CG level. Here we present a reduced set of parameters derived to treat a hybrid interface in DNA simulations. Our method allows us to forthrightly link a state-of-the-art force field for AA simulations of DNA with a CG representation developed by our group. We show that no modification is needed for any of the existing residues (neither AA nor CG). Only the bonding parameters at the hybrid interface are enough to produce a smooth transition of electrostatic, mechanic and dynamic features in different AA/CG systems, which are studied by molecular dynamics simulations using an implicit solvent. The simplicity of the approach potentially permits us to study the effect of mutations/modifications as well as DNA binding molecules at the atomistic level within a significantly larger DNA scaffold considered at the CG level. Since all the interactions are computed within the same classical Hamiltonian, the extension to a quantum/classical/coarse-grain multilayer approach using QM/MM modules implemented in widely used simulation packages is straightforward.

  7. DFT studies of carbohydrate solvation: II. MD-DFTr of a super-molecule complex of glucose, explicit waters, and an implicit solvent (COSMO)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    MD-DFTr studies are carried out on the super-molecule solvated complexes of glucose described in paper I. Included were ten explicit water molecules and an implicit solvation model, COSMO, superimposed upon the complex. Starting configurations were taken from DFTr optimized complexes resulting from ...

  8. Preformed template fluctuations promote fibril formation: Insights from lattice and all-atom models

    SciTech Connect

    Kouza, Maksim Kolinski, Andrzej; Co, Nguyen Truong; Nguyen, Phuong H.; Li, Mai Suan

    2015-04-14

    Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Despite the fact that the fibril formation process is very slow and thus poses a significant challenge for theoretical and experimental studies, a number of alternative pictures of molecular mechanisms of amyloid fibril formation have been recently proposed. What seems to be common for the majority of the proposed models is that fibril elongation involves the formation of pre-nucleus seeds prior to the creation of a critical nucleus. Once the size of the pre-nucleus seed reaches the critical nucleus size, its thermal fluctuations are expected to be small and the resulting nucleus provides a template for sequential (one-by-one) accommodation of added monomers. The effect of template fluctuations on fibril formation rates has not been explored either experimentally or theoretically so far. In this paper, we make the first attempt at solving this problem by two sets of simulations. To mimic small template fluctuations, in one set, monomers of the preformed template are kept fixed, while in the other set they are allowed to fluctuate. The kinetics of addition of a new peptide onto the template is explored using all-atom simulations with explicit water and the GROMOS96 43a1 force field and simple lattice models. Our result demonstrates that preformed template fluctuations can modulate protein aggregation rates and pathways. The association of a nascent monomer with the template obeys the kinetics partitioning mechanism where the intermediate state occurs in a fraction of routes to the protofibril. It was shown that template immobility greatly increases the time of incorporating a new peptide into the preformed template compared to the fluctuating template case. This observation has also been confirmed by simulation using lattice models and may be invoked to understand the role of template fluctuations in

  9. Preformed template fluctuations promote fibril formation: insights from lattice and all-atom models.

    PubMed

    Kouza, Maksim; Co, Nguyen Truong; Nguyen, Phuong H; Kolinski, Andrzej; Li, Mai Suan

    2015-04-14

    Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite the fact that the fibril formation process is very slow and thus poses a significant challenge for theoretical and experimental studies, a number of alternative pictures of molecular mechanisms of amyloid fibril formation have been recently proposed. What seems to be common for the majority of the proposed models is that fibril elongation involves the formation of pre-nucleus seeds prior to the creation of a critical nucleus. Once the size of the pre-nucleus seed reaches the critical nucleus size, its thermal fluctuations are expected to be small and the resulting nucleus provides a template for sequential (one-by-one) accommodation of added monomers. The effect of template fluctuations on fibril formation rates has not been explored either experimentally or theoretically so far. In this paper, we make the first attempt at solving this problem by two sets of simulations. To mimic small template fluctuations, in one set, monomers of the preformed template are kept fixed, while in the other set they are allowed to fluctuate. The kinetics of addition of a new peptide onto the template is explored using all-atom simulations with explicit water and the GROMOS96 43a1 force field and simple lattice models. Our result demonstrates that preformed template fluctuations can modulate protein aggregation rates and pathways. The association of a nascent monomer with the template obeys the kinetics partitioning mechanism where the intermediate state occurs in a fraction of routes to the protofibril. It was shown that template immobility greatly increases the time of incorporating a new peptide into the preformed template compared to the fluctuating template case. This observation has also been confirmed by simulation using lattice models and may be invoked to understand the role of template fluctuations in

  10. Multi-scale modeling of electronic spectra of three aromatic amino acids: importance of conformational averaging and explicit solute-solvent interactions.

    PubMed

    Štěpánek, Petr; Bouř, Petr

    2014-10-14

    Electronic transitions in the ultraviolet and visible spectral range can reveal a wealth of information about biomolecular geometry and interactions, such as those involved in protein folding. However, the modeling that provides the necessary link between spectral shapes and the structure is often difficult even for seemingly simple systems. To understand as to how conformational equilibria and solute-solvent interaction influence spectral intensities, we collected absorption (UV-vis), electronic circular dichroism (ECD), and magnetic circular dichroism (MCD) spectra of phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) zwitterions in aqueous solutions, and compared them with quantum-chemical simulations. These aromatic amino acids provide a relatively strong signal in the accessible wavelength range. At the same time, they allow for a relatively accurate modeling. Energies and intensities of spectral bands were reproduced by the time-dependent density functional theory (TD DFT). The solvent was approximated by a continuum as well as clusters containing solvent molecules from the first hydration sphere. The ECD signal was found to be strongly dependent on molecular conformation, and the dependence was much weaker in UV-vis and MCD spectra. All spectral intensities, however, were significantly affected by the solvent approximation; especially for ECD and MCD the usual polarizable continuum solvent model did not yield satisfactory spectral shapes. On the other hand, averaging of the clusters obtained from molecular dynamics simulations provided an unprecedented agreement with the experiment. Proper modeling of the interactions with the environment thus makes the information about the molecular structure, as obtained from the electronic spectra, more accurate and reliable.

  11. All-atom structural models for complexes of insulin-like growth factors IGF1 and IGF2 with their cognate receptor.

    PubMed

    Vashisth, Harish; Abrams, Cameron F

    2010-07-16

    Type 1 insulin-like growth factor receptor (IGF1R) is a membrane-spanning glycoprotein of the insulin receptor family that has been implicated in a variety of cancers. The key questions related to molecular mechanisms governing ligand recognition by IGF1R remain unanswered, partly due to the lack of testable structural models of apo or ligand-bound receptor complexes. Using a homology model of the IGF1R ectodomain IGF1RDeltabeta, we present the first experimentally consistent all-atom structural models of IGF1/IGF1RDeltabeta and IGF2/IGF1RDeltabeta complexes. Our explicit-solvent molecular dynamics (MD) simulation of apo-IGF1RDeltabeta shows that it displays asymmetric flexibility mechanisms that result in one of two binding pockets accessible to growth factors IGF1 and IGF2, as demonstrated via an MD-assisted Monte Carlo docking procedure. Our MD-generated ensemble of structures of apo and IGF1-bound IGF1RDeltabeta agrees reasonably well with published small-angle X-ray scattering data. We observe simultaneous contacts of each growth factor with sites 1 and 2 of IGF1R, suggesting cross-linking of receptor subunits. Our models provide direct evidence in favor of suggested electrostatic complementarity between the C-domain (IGF1) and the cysteine-rich domain (IGF1R). Our IGF1/IGF1RDeltabeta model provides structural bases for the observation that a single IGF1 molecule binds to IGF1RDeltabeta at low concentrations in small-angle X-ray scattering studies. We also suggest new possible structural bases for differences in the affinities of insulin, IGF1, and IGF2 for their noncognate receptors.

  12. All-atom molecular dynamics studies of the full-length β-amyloid peptides

    NASA Astrophysics Data System (ADS)

    Luttmann, Edgar; Fels, Gregor

    2006-03-01

    β-Amyloid peptides are believed to play an essential role in Alzheimer's disease (AD), due to their sedimentation in the form of β-amyloid aggregates in the brain of AD-patients, and the in vitro neurotoxicity of oligomeric aggregates. The monomeric peptides come in different lengths of 39-43 residues, of which the 42 alloform seems to be most strongly associated with AD-symptoms. Structural information on these peptides to date comes from NMR studies in acidic solutions, organic solvents, or on shorter fragments of the peptide. In addition X-ray and solid-state NMR investigations of amyloid fibrils yield insight into the structure of the final aggregate and therefore define the endpoint of any conformational change of an Aβ-monomer along the aggregation process. The conformational changes necessary to connect the experimentally known conformations are not yet understood and this process is an active field of research. In this paper, we report results from all-atom molecular dynamics simulations based on experimental data from four different peptides of 40 amino acids and two peptides consisting of 42 amino acids. The simulations allow for the analysis of intramolecular interactions and the role of structural features. In particular, they show the appearance of β-turn in the region between amino acid 21 and 33, forming a hook-like shape as it is known to exist in the fibrillar Aβ-structures. This folding does not depend on the formation of a salt bridge between Asp-23 and Lys-28 but requires the Aβ(1-42) as such structure was not observed in the shorter system Aβ(1-40).

  13. All-atom and coarse-grained simulations of the forced unfolding pathways of the SNARE complex.

    PubMed

    Zheng, Wenjun

    2014-07-01

    The SNARE complex, consisting of three proteins (VAMP2, syntaxin, and SNAP-25), is thought to drive membrane fusion by assembling into a four-helix bundle through a zippering process. In support of the above zippering model, a recent single-molecule optical tweezers experiment by Gao et al. revealed a sequential unzipping of SNARE along VAMP2 in the order of the linker domain → the C-terminal domain → the N-terminal domain. To offer detailed structural insights to this unzipping process, we have performed all-atom and coarse-grained steered molecular dynamics (sMD) simulations of the forced unfolding pathways of SNARE using different models and force fields. Our findings are summarized as follows: First, the sMD simulations based on either an all-atom force field (with an implicit solvent model) or a coarse-grained Go model were unable to capture the forced unfolding pathway of SNARE as observed by Gao et al., which may be attributed to insufficient simulation time and inaccurate force fields. Second, the sMD simulations based on a reparameterized coarse-grained model (i.e., modified elastic network model) were able to predict a sequential unzipping of SNARE in good agreement with the findings by Gao et al. The key to this success is to reparameterize the intrahelix and interhelix nonbonded force constants against the pair-wise residue-residue distance fluctuations collected from all-atom MD simulations of SNARE. Therefore, our finding supports the importance of accurately describing the inherent dynamics/flexibility of SNARE (in the absence of force), in order to correctly simulate its unfolding behaviors under force. This study has established a useful computational framework for future studies of the zippering function of SNARE and its perturbations by point mutations with amino-acid level of details, and more generally the forced unfolding pathways of other helix bundle proteins.

  14. 129Xe NMR chemical shift in Xe@C60 calculated at experimental conditions: essential role of the relativity, dynamics, and explicit solvent.

    PubMed

    Standara, Stanislav; Kulhánek, Petr; Marek, Radek; Straka, Michal

    2013-08-15

    The isotropic (129)Xe nuclear magnetic resonance (NMR) chemical shift (CS) in Xe@C60 dissolved in liquid benzene was calculated by piecewise approximation to faithfully simulate the experimental conditions and to evaluate the role of different physical factors influencing the (129)Xe NMR CS. The (129)Xe shielding constant was obtained by averaging the (129)Xe nuclear magnetic shieldings calculated for snapshots obtained from the molecular dynamics trajectory of the Xe@C60 system embedded in a periodic box of benzene molecules. Relativistic corrections were added at the Breit-Pauli perturbation theory (BPPT) level, included the solvent, and were dynamically averaged. It is demonstrated that the contribution of internal dynamics of the Xe@C60 system represents about 8% of the total nonrelativistic NMR CS, whereas the effects of dynamical solvent add another 8%. The dynamically averaged relativistic effects contribute by 9% to the total calculated (129)Xe NMR CS. The final theoretical value of 172.7 ppm corresponds well to the experimental (129)Xe CS of 179.2 ppm and lies within the estimated errors of the model. The presented computational protocol serves as a prototype for calculations of (129)Xe NMR parameters in different Xe atom guest-host systems.

  15. All-Atom Structural Models of the Transmembrane Domains of Insulin and Type 1 Insulin-Like Growth Factor Receptors.

    PubMed

    Mohammadiarani, Hossein; Vashisth, Harish

    2016-01-01

    The receptor tyrosine kinase superfamily comprises many cell-surface receptors including the insulin receptor (IR) and type 1 insulin-like growth factor receptor (IGF1R) that are constitutively homodimeric transmembrane glycoproteins. Therefore, these receptors require ligand-triggered domain rearrangements rather than receptor dimerization for activation. Specifically, binding of peptide ligands to receptor ectodomains transduces signals across the transmembrane domains for trans-autophosphorylation in cytoplasmic kinase domains. The molecular details of these processes are poorly understood in part due to the absence of structures of full-length receptors. Using MD simulations and enhanced conformational sampling algorithms, we present all-atom structural models of peptides containing 51 residues from the transmembrane and juxtamembrane regions of IR and IGF1R. In our models, the transmembrane regions of both receptors adopt helical conformations with kinks at Pro961 (IR) and Pro941 (IGF1R), but the C-terminal residues corresponding to the juxtamembrane region of each receptor adopt unfolded and flexible conformations in IR as opposed to a helix in IGF1R. We also observe that the N-terminal residues in IR form a kinked-helix sitting at the membrane-solvent interface, while homologous residues in IGF1R are unfolded and flexible. These conformational differences result in a larger tilt-angle of the membrane-embedded helix in IGF1R in comparison to IR to compensate for interactions with water molecules at the membrane-solvent interfaces. Our metastable/stable states for the transmembrane domain of IR, observed in a lipid bilayer, are consistent with a known NMR structure of this domain determined in detergent micelles, and similar states in IGF1R are consistent with a previously reported model of the dimerized transmembrane domains of IGF1R. Our all-atom structural models suggest potentially unique structural organization of kinase domains in each receptor.

  16. Deriving Coarse-Grained Charges from All-Atom Systems: An Analytic Solution.

    PubMed

    McCullagh, Peter; Lake, Peter T; McCullagh, Martin

    2016-09-13

    An analytic method to assign optimal coarse-grained charges based on electrostatic potential matching is presented. This solution is the infinite size and density limit of grid-integration charge-fitting and is computationally more efficient by several orders of magnitude. The solution is also minimized with respect to coarse-grained positions which proves to be an extremely important step in reproducing the all-atom electrostatic potential. The joint optimal-charge optimal-position coarse-graining procedure is applied to a number of aggregating proteins using single-site per amino acid resolution. These models provide a good estimate of both the vacuum and Debye-Hückel screened all-atom electrostatic potentials in the vicinity and in the far-field of the protein. Additionally, these coarse-grained models are shown to approximate the all-atom dimerization electrostatic potential energy of 10 aggregating proteins with good accuracy.

  17. Calculating distribution coefficients based on multi-scale free energy simulations: an evaluation of MM and QM/MM explicit solvent simulations of water-cyclohexane transfer in the SAMPL5 challenge

    NASA Astrophysics Data System (ADS)

    König, Gerhard; Pickard, Frank C.; Huang, Jing; Simmonett, Andrew C.; Tofoleanu, Florentina; Lee, Juyong; Dral, Pavlo O.; Prasad, Samarjeet; Jones, Michael; Shao, Yihan; Thiel, Walter; Brooks, Bernard R.

    2016-11-01

    One of the central aspects of biomolecular recognition is the hydrophobic effect, which is experimentally evaluated by measuring the distribution coefficients of compounds between polar and apolar phases. We use our predictions of the distribution coefficients between water and cyclohexane from the SAMPL5 challenge to estimate the hydrophobicity of different explicit solvent simulation techniques. Based on molecular dynamics trajectories with the CHARMM General Force Field, we compare pure molecular mechanics (MM) with quantum-mechanical (QM) calculations based on QM/MM schemes that treat the solvent at the MM level. We perform QM/MM with both density functional theory (BLYP) and semi-empirical methods (OM1, OM2, OM3, PM3). The calculations also serve to test the sensitivity of partition coefficients to solute polarizability as well as the interplay of the quantum-mechanical region with the fixed-charge molecular mechanics environment. Our results indicate that QM/MM with both BLYP and OM2 outperforms pure MM. However, this observation is limited to a subset of cases where convergence of the free energy can be achieved.

  18. Replica exchange simulation of reversible folding/unfolding of the Trp-cage miniprotein in explicit solvent: on the structure and possible role of internal water.

    PubMed

    Paschek, Dietmar; Nymeyer, Hugh; García, Angel E

    2007-03-01

    We simulate the folding/unfolding equilibrium of the 20-residue miniprotein Trp-cage. We use replica exchange molecular dynamics simulations of the AMBER94 atomic detail model of the protein explicitly solvated by water, starting from a completely unfolded configuration. We employ a total of 40 replicas, covering the temperature range between 280 and 538 K. Individual simulation lengths of 100 ns sum up to a total simulation time of about 4 micros. Without any bias, we observe the folding of the protein into the native state with an unfolding-transition temperature of about 440 K. The native state is characterized by a distribution of root mean square distances (RMSD) from the NMR data that peaks at 1.8A, and is as low as 0.4A. We show that equilibration times of about 40 ns are required to yield convergence. A folded configuration in the entire extended ensemble is found to have a lifetime of about 31 ns. In a clamp-like motion, the Trp-cage opens up during thermal denaturation. In line with fluorescence quenching experiments, the Trp-residue sidechain gets hydrated when the protein opens up, roughly doubling the number of water molecules in the first solvation shell. We find the helical propensity of the helical domain of Trp-cage rather well preserved even at very high temperatures. In the folded state, we can identify states with one and two buried internal water molecules interconnecting parts of the Trp-cage molecule by hydrogen bonds. The loss of hydrogen bonds of these buried water molecules in the folded state with increasing temperature is likely to destabilize the folded state at elevated temperatures.

  19. Reduced Cβ statistical potentials can outperform all-atom potentials in decoy identification

    PubMed Central

    Fitzgerald, James E.; Jha, Abhishek K.; Colubri, Andres; Sosnick, Tobin R.; Freed, Karl F.

    2007-01-01

    We developed a series of statistical potentials to recognize the native protein from decoys, particularly when using only a reduced representation in which each side chain is treated as a single Cβ atom. Beginning with a highly successful all-atom statistical potential, the Discrete Optimized Protein Energy function (DOPE), we considered the implications of including additional information in the all-atom statistical potential and subsequently reducing to the Cβ representation. One of the potentials includes interaction energies conditional on backbone geometries. A second potential separates sequence local from sequence nonlocal interactions and introduces a novel reference state for the sequence local interactions. The resultant potentials perform better than the original DOPE statistical potential in decoy identification. Moreover, even upon passing to a reduced Cβ representation, these statistical potentials outscore the original (all-atom) DOPE potential in identifying native states for sets of decoys. Interestingly, the backbone-dependent statistical potential is shown to retain nearly all of the information content of the all-atom representation in the Cβ representation. In addition, these new statistical potentials are combined with existing potentials to model hydrogen bonding, torsion energies, and solvation energies to produce even better performing potentials. The ability of the Cβ statistical potentials to accurately represent protein interactions bodes well for computational efficiency in protein folding calculations using reduced backbone representations, while the extensions to DOPE illustrate general principles for improving knowledge-based potentials. PMID:17893359

  20. Folding of proteins with an all-atom Go-model.

    PubMed

    Wu, L; Zhang, J; Qin, M; Liu, F; Wang, W

    2008-06-21

    The Go-like potential at a residual level has been successfully applied to the folding of proteins in many previous works. However, taking into consideration more detailed structural information in the atomic level, the definition of contacts used in these traditional Go-models may not be suitable for all-atom simulations. Here, in this work, we develop a rational definition of contacts considering the screening effect in the crowded intramolecular environment. In such a scheme, a large amount of screened atom pairs are excluded and the number of contacts is decreased compared to the case of the traditional definition. These contacts defined by such a new definition are compatible with the all-atom representation of protein structures. To verify the rationality of the new definition of contacts, the folding of proteins CI2 and SH3 is simulated by all-atom molecular dynamics simulations. A high folding cooperativity and good correlation of the simulated Phi-values with those obtained experimentally, especially for CI2, are found. This suggests that the all-atom Go-model is improved compared to the traditional Go-model. Based on the comparison of the Phi-values, the roles of side chains in the folding are discussed, and it is concluded that the side-chain structures are more important for local contacts in determining the transition state structures. Moreover, the relations between side chain and backbone orderings are also discussed.

  1. Folding peptides and proteins with all-atom physics: methods and applications

    NASA Astrophysics Data System (ADS)

    Shell, M. Scott

    2008-03-01

    Computational methods offer powerful tools for investigating proteins and peptides at the molecular-level; however, it has proven challenging to reproduce the long time scale folding processes of these molecules at a level that is both faithful to the atomic driving forces and attainable with modern commodity cluster computing. Alternatively, the past decade has seen significant progress in using bioinformatics-based approaches to infer the three dimensional native structures of proteins, drawing upon extensive knowledge databases of known protein structures [1]. These methods work remarkably well when a homologous protein can be found to provide a structural template for a candidate sequence. However, in cases where homology to database proteins is low, where the folding pathway is of interest, or where conformational flexibility is substantial---as in many emerging protein and peptide technologies---bioinformatics methods perform poorly. There is therefore great interest in seeing purely physics-based approaches succeed. We discuss a purely physics-based, database-free folding method, relying on proper thermal sampling (replica exchange molecular dynamics) and molecular potential energy functions. In order to surmount the tremendous computational demands of all-atom folding simulations, our approach implements a conformational search strategy based on a putative protein folding mechanism called zipping and assembly [2-4]. That is, we explicitly seek out potential folding pathways inferred from short simulations, and iteratively pursue all such routes by coaxing a polypeptide chain along them. The method is called the Zipping and Assembly Method (ZAM) and it works in two parts: (1) the full polypeptide chain is broken into small fragments that are first simulated independently and then successively re-assembled into larger segments with further sampling, and (2) consistently stable structure in fragments is detected and locked into place, in order to avoid re

  2. Structure prediction for CASP7 targets using extensive all-atom refinement with Rosetta@home.

    PubMed

    Das, Rhiju; Qian, Bin; Raman, Srivatsan; Vernon, Robert; Thompson, James; Bradley, Philip; Khare, Sagar; Tyka, Michael D; Bhat, Divya; Chivian, Dylan; Kim, David E; Sheffler, William H; Malmström, Lars; Wollacott, Andrew M; Wang, Chu; Andre, Ingemar; Baker, David

    2007-01-01

    We describe predictions made using the Rosetta structure prediction methodology for both template-based modeling and free modeling categories in the Seventh Critical Assessment of Techniques for Protein Structure Prediction. For the first time, aggressive sampling and all-atom refinement could be carried out for the majority of targets, an advance enabled by the Rosetta@home distributed computing network. Template-based modeling predictions using an iterative refinement algorithm improved over the best existing templates for the majority of proteins with less than 200 residues. Free modeling methods gave near-atomic accuracy predictions for several targets under 100 residues from all secondary structure classes. These results indicate that refinement with an all-atom energy function, although computationally expensive, is a powerful method for obtaining accurate structure predictions.

  3. Resolution-Adapted All-Atomic and Coarse-Grained Model for Biomolecular Simulations.

    PubMed

    Shen, Lin; Hu, Hao

    2014-06-10

    We develop here an adaptive multiresolution method for the simulation of complex heterogeneous systems such as the protein molecules. The target molecular system is described with the atomistic structure while maintaining concurrently a mapping to the coarse-grained models. The theoretical model, or force field, used to describe the interactions between two sites is automatically adjusted in the simulation processes according to the interaction distance/strength. Therefore, all-atomic, coarse-grained, or mixed all-atomic and coarse-grained models would be used together to describe the interactions between a group of atoms and its surroundings. Because the choice of theory is made on the force field level while the sampling is always carried out in the atomic space, the new adaptive method preserves naturally the atomic structure and thermodynamic properties of the entire system throughout the simulation processes. The new method will be very useful in many biomolecular simulations where atomistic details are critically needed.

  4. Structure prediction for CASP8 with all-atom refinement using Rosetta.

    PubMed

    Raman, Srivatsan; Vernon, Robert; Thompson, James; Tyka, Michael; Sadreyev, Ruslan; Pei, Jimin; Kim, David; Kellogg, Elizabeth; DiMaio, Frank; Lange, Oliver; Kinch, Lisa; Sheffler, Will; Kim, Bong-Hyun; Das, Rhiju; Grishin, Nick V; Baker, David

    2009-01-01

    We describe predictions made using the Rosetta structure prediction methodology for the Eighth Critical Assessment of Techniques for Protein Structure Prediction. Aggressive sampling and all-atom refinement were carried out for nearly all targets. A combination of alignment methodologies was used to generate starting models from a range of templates, and the models were then subjected to Rosetta all atom refinement. For the 64 domains with readily identified templates, the best submitted model was better than the best alignment to the best template in the Protein Data Bank for 24 cases, and improved over the best starting model for 43 cases. For 13 targets where only very distant sequence relationships to proteins of known structure were detected, models were generated using the Rosetta de novo structure prediction methodology followed by all-atom refinement; in several cases the submitted models were better than those based on the available templates. Of the 12 refinement challenges, the best submitted model improved on the starting model in seven cases. These improvements over the starting template-based models and refinement tests demonstrate the power of Rosetta structure refinement in improving model accuracy.

  5. Free Energetics of Carbon Nanotube Association in Aqueous Inorganic NaI Salt Solutions: Temperature Effects using All-Atom Molecular Dynamics Simulations

    PubMed Central

    Ou, Shu-Ching; Cui, Di; Wezowicz, Matthew; Taufer, Michela; Patel, Sandeep

    2015-01-01

    In this study we examine the temperature dependence of free energetics of nanotube association by using GPU-enabled all-atom molecular dynamics simulations (FEN ZI) with two (10,10) single-walled carbon nanotubes in 3 m NaI aqueous salt solution. Results suggest that the free energy, enthalpy and entropy changes for the association process are all reduced at the high temperature, in agreement with previous investigations using other hydrophobes. Via the decomposition of free energy into individual components, we found that solvent contribution (including water, anion and cation contributions) is correlated with the spatial distribution of the corresponding species and is influenced distinctly by the temperature. We studied the spatial distribution and the structure of the solvent in different regions: intertube, intra-tube and the bulk solvent. By calculating the fluctuation of coarse-grained tube-solvent surfaces, we found that tube-water interfacial fluctuation exhibits the strongest temperature dependence. By taking ions to be a solvent-like medium in the absence of water, tube-anion interfacial fluctuation also shows similar but weaker dependence on temperature, while tube-cation interfacial fluctuation shows no dependence in general. These characteristics are discussed via the malleability of their corresponding solvation shells relative to the nanotube surface. Hydrogen bonding profiles and tetrahedrality of water arrangement are also computed to compare the structure of solvent in the solvent bulk and intertube region. The hydrophobic confinement induces a relatively lower concentration environment in the intertube region, therefore causing different intertube solvent structures which depend on the tube separation. This study is relevant in the continuing discourse on hydrophobic interactions (as they impact generally a broad class of phenomena in biology, biochemistry, and materials science and soft condensed matter research), and interpretations of

  6. Evaluation of protein-protein docking model structures using all-atom molecular dynamics simulations combined with the solution theory in the energy representation.

    PubMed

    Takemura, Kazuhiro; Guo, Hao; Sakuraba, Shun; Matubayasi, Nobuyuki; Kitao, Akio

    2012-12-07

    We propose a method to evaluate binding free energy differences among distinct protein-protein complex model structures through all-atom molecular dynamics simulations in explicit water using the solution theory in the energy representation. Complex model structures are generated from a pair of monomeric structures using the rigid-body docking program ZDOCK. After structure refinement by side chain optimization and all-atom molecular dynamics simulations in explicit water, complex models are evaluated based on the sum of their conformational and solvation free energies, the latter calculated from the energy distribution functions obtained from relatively short molecular dynamics simulations of the complex in water and of pure water based on the solution theory in the energy representation. We examined protein-protein complex model structures of two protein-protein complex systems, bovine trypsin/CMTI-1 squash inhibitor (PDB ID: 1PPE) and RNase SA/barstar (PDB ID: 1AY7), for which both complex and monomer structures were determined experimentally. For each system, we calculated the energies for the crystal complex structure and twelve generated model structures including the model most similar to the crystal structure and very different from it. In both systems, the sum of the conformational and solvation free energies tended to be lower for the structure similar to the crystal. We concluded that our energy calculation method is useful for selecting low energy complex models similar to the crystal structure from among a set of generated models.

  7. An all-atom simulation study of the ordering of liquid squalane near a solid surface

    NASA Astrophysics Data System (ADS)

    Tsige, Mesfin; Patnaik, Soumya S.

    2008-05-01

    An all-atom molecular dynamics study using the OPLS force field has been carried out to obtain new insights in to the orientation and ordering of liquid squalane near a solid surface. As observed in previous experiments, the squalane molecules closest to a SiO 2 substrate are found to be tightly bound with their molecular axis preferentially parallel to the interface. Unlike linear alkanes, the squalane molecules are also found to lie preferentially parallel to the liquid/vapor interface. The simulation results predict that the molecular plane orientation of the squalane molecules changes from mainly parallel to perpendicular to the substrate in going further away from the substrate.

  8. DFT study of nitroxide radicals: explicit modeling of solvent effects on the structural and electronic characteristics of 4-amino-2,2,6,6-tetramethyl-piperidine-N-oxyl.

    PubMed

    Ikryannikova, Larissa N; Ustynyuk, Leila Yu; Tikhonov, Alexander N

    2010-05-01

    An explicit DFT modeling of water surroundings on the electron paramagnetic resonance properties of 4-amino-2,2,6,6-tetramethyl-piperidine-N-oxyl (TA) has been performed. A stepwise hydration of TA is accompanied with certain changes in geometrical parameters (bond lengths and angles) and redistribution of partial electric charges in TA. An aqueous cluster of 45 water molecules can be considered as an appropriate model for a complete aqueous shell around TA, although most of the structural and electronic characteristics of TA already converge at about 10 water molecules. Water surroundings induce an increase in electron spin density on the nitrogen atom of the nitroxide fragment due to stabilization of the polar resonance structure > N(+*)-O(-) at the expense of less polar structure > N-O*. The water-induced rise of the isotropic splitting constant a(iso), calculated from the contact term of the hyperfine interaction, comprises Deltaa(iso)(rho(N2)) = 2.2-2.5 G, which is typical of experimental value for TA. There are two contributions to the solvent effect on the a(iso)(rho(N2)) value: the redistribution of spin density in the nitroxide fragment (polarity effect) and water-induced distortions of TA geometry. Microscopic variations in a hydrogen-bonded water network cause noticeable fluctuations of the splitting constant a(iso)(rho(N2)). Calculations of the atomic spin density (sigma(N2)) allowed us to compute the splitting constant from the relationship a(iso)(sigma(N2)) = Qsigma(N2), where Q = 36.2 G. A practical advantage of using this relationship is that it gives 'smoothed' values of the splitting constant, which are sensitive to the environment polarity but remain tolerant to microscopic fluctuations of the hydrogen-bonded water network around a spin-label molecule.

  9. An all-atom model of the structure of human copper transporter 1.

    PubMed

    Tsigelny, Igor F; Sharikov, Yuriy; Greenberg, Jerry P; Miller, Mark A; Kouznetsova, Valentina L; Larson, Christopher A; Howell, Stephen B

    2012-07-01

    Human copper transporter 1 (hCTR1) is the major high affinity copper influx transporter in mammalian cells that also mediates uptake of the cancer chemotherapeutic agent cisplatin. A low resolution structure of hCTR1 determined by cryoelectron microscopy was recently published. Several protein structure simulation techniques were used to create an all-atom model of this important transporter using the low resolution structure as a starting point. The all-atom model provides new insights into the roles of specific residues of the N-terminal extracellular domain, the intracellular loop, and C-terminal region in metal ion transport. In particular, the model demonstrates that the central region of the pore contains four sets of methionine triads in the intramembranous region. The structure confirms that two triads of methionine residues delineate the intramembranous region of the transporter, and further identifies two additional methionine triads that are located in the extracellular N-terminal part of the transporter. Together, the four triads create a structure that promotes stepwise transport of metal ions into and then through the intramembranous channel of the transporter via transient thioether bonds to methionine residues. Putative copper-binding sites in the hCTR1 trimer were identified by a program developed by us for prediction of metal-binding sites. These sites correspond well with the known effects of mutations on the ability of the protein to transport copper and cisplatin.

  10. An All-Atom Model of the Structure of Human Copper Transporter 1

    PubMed Central

    Sharikov, Yuriy; Greenberg, Jerry P.; Miller, Mark A.; Kouznetsova, Valentina L.; Larson, Christopher A.; Howell, Stephen B.

    2013-01-01

    Human copper transporter 1 (hCTR1) is the major high affinity copper influx transporter in mammalian cells that also mediates uptake of the cancer chemotherapeutic agent cisplatin. A low resolution structure of hCTR1 determined by cryoelectron microscopy was recently published. Several protein structure simulation techniques were used to create an all-atom model of this important transporter using the low resolution structure as a starting point. The all-atom model provides new insights into the roles of specific residues of the N-terminal extracellular domain, the intracellular loop, and C-terminal region in metal ion transport. In particular, the model demonstrates that the central region of the pore contains four sets of methionine triads in the intramembranous region. The structure confirms that two triads of methionine residues delineate the intramembranous region of the transporter, and further identifies two additional methionine triads that are located in the extracellular N-terminal part of the transporter. Together, the four triads create a structure that promotes stepwise transport of metal ions into and then through the intramembranous channel of the transporter via transient thioether bonds to methionine residues. Putative copper-binding sites in the hCTR1 trimer were identified by a program developed by us for prediction of metal-binding sites. These sites correspond well with the known effects of mutations on the ability of the protein to transport copper and cisplatin. PMID:22569840

  11. From Aβ Filament to Fibril: Molecular Mechanism of Surface-Activated Secondary Nucleation from All-Atom MD Simulations.

    PubMed

    Schwierz, Nadine; Frost, Christina V; Geissler, Phillip L; Zacharias, Martin

    2017-02-02

    Secondary nucleation pathways in which existing amyloid fibrils catalyze the formation of new aggregates and neurotoxic oligomers are of immediate importance for the onset and progression of Alzheimer's disease. Here, we apply extensive all-atom molecular dynamics simulations in explicit water to study surface-activated secondary nucleation pathways at the extended lateral β-sheet surface of a preformed Aβ9-40 filament. Calculation of free-energy profiles allows us to determine binding free energies and conformational intermediates for nucleation complexes consisting of 1-4 Aβ peptides. In addition, we combine the free-energy profiles with position-dependent diffusion profiles to extract complementary kinetic information and macroscopic growth rates. Single monomers bind to the β-sheet surface in a disordered, hydrophobically collapsed conformation, whereas dimers and larger oligomers can retain a cross-β conformation resembling a more ordered fibril structure. The association processes during secondary nucleation follow a dock/lock mechanism consisting of a fast initial encounter phase (docking) and a slow structural rearrangement phase (locking). The major driving forces for surface-activated secondary nucleation are the release of a large number of hydration water molecules and the formation of hydrophobic interface contacts, the latter being in contrast to the elongation process at filament tips, which is dominated by the formation of stable and highly specific interface hydrogen bonds. The calculated binding free energies and the association rates for the attachment of Aβ monomers and oligomers to the extended lateral β-sheet surface of the filament seed are higher compared to those for elongation at the filament tips, indicating that secondary nucleation pathways can become important once a critical concentration of filaments has formed.

  12. All-Atom Continuous Constant pH Molecular Dynamics With Particle Mesh Ewald and Titratable Water.

    PubMed

    Huang, Yandong; Chen, Wei; Wallace, Jason A; Shen, Jana

    2016-11-08

    Development of a pH stat to properly control solution pH in biomolecular simulations has been a long-standing goal in the community. Toward this goal recent years have witnessed the emergence of the so-called constant pH molecular dynamics methods. However, the accuracy and generality of these methods have been hampered by the use of implicit-solvent models or truncation-based electrostatic schemes. Here we report the implementation of the particle mesh Ewald (PME) scheme into the all-atom continuous constant pH molecular dynamics (CpHMD) method, enabling CpHMD to be performed with a standard MD engine at a fractional added computational cost. We demonstrate the performance using pH replica-exchange CpHMD simulations with titratable water for a stringent test set of proteins, HP36, BBL, HEWL, and SNase. With the sampling time of 10 ns per replica, most pKa's are converged, yielding the average absolute and root-mean-square deviations of 0.61 and 0.77, respectively, from experiment. Linear regression of the calculated vs experimental pKa shifts gives a correlation coefficient of 0.79, a slope of 1, and an intercept near 0. Analysis reveals inadequate sampling of structure relaxation accompanying a protonation-state switch as a major source of the remaining errors, which are reduced as simulation prolongs. These data suggest PME-based CpHMD can be used as a general tool for pH-controlled simulations of macromolecular systems in various environments, enabling atomic insights into pH-dependent phenomena involving not only soluble proteins but also transmembrane proteins, nucleic acids, surfactants, and polysaccharides.

  13. Characterization of biaryl torsional energetics and its treatment in OPLS all-atom force fields.

    PubMed

    Dahlgren, Markus K; Schyman, Patric; Tirado-Rives, Julian; Jorgensen, William L

    2013-05-24

    The frequency of biaryl substructures in a database of approved oral drugs has been analyzed. This led to designation of 20 prototypical biaryls plus 10 arylpyridinones for parametrization in the OPLS all-atom force fields. Bond stretching, angle-bending, and torsional parameters were developed to reproduce the MP2 geometries and torsional energy profiles. The transferability of the new parameters was tested through their application to three additional biaryls. The torsional energetics for the 33 biaryl molecules are analyzed and factors leading to preferences for planar and nonplanar geometries are identified. For liquid biphenyl, the computed density and heat of vaporization at the boiling point (255 °C) are also reported.

  14. All-Atom Molecular Dynamics of Virus Capsids as Drug Targets

    PubMed Central

    2016-01-01

    Virus capsids are protein shells that package the viral genome. Although their morphology and biological functions can vary markedly, capsids often play critical roles in regulating viral infection pathways. A detailed knowledge of virus capsids, including their dynamic structure, interactions with cellular factors, and the specific roles that they play in the replication cycle, is imperative for the development of antiviral therapeutics. The following Perspective introduces an emerging area of computational biology that focuses on the dynamics of virus capsids and capsid–protein assemblies, with particular emphasis on the effects of small-molecule drug binding on capsid structure, stability, and allosteric pathways. When performed at chemical detail, molecular dynamics simulations can reveal subtle changes in virus capsids induced by drug molecules a fraction of their size. Here, the current challenges of performing all-atom capsid–drug simulations are discussed, along with an outlook on the applicability of virus capsid simulations to reveal novel drug targets. PMID:27128262

  15. Comparing a simple theoretical model for protein folding with all-atom molecular dynamics simulations.

    PubMed

    Henry, Eric R; Best, Robert B; Eaton, William A

    2013-10-29

    Advances in computing have enabled microsecond all-atom molecular dynamics trajectories of protein folding that can be used to compare with and test critical assumptions of theoretical models. We show that recent simulations by the Shaw group (10, 11, 14, 15) are consistent with a key assumption of an Ising-like theoretical model that native structure grows in only a few regions of the amino acid sequence as folding progresses. The distribution of mechanisms predicted by simulating the master equation of this native-centric model for the benchmark villin subdomain, with only two adjustable thermodynamic parameters and one temperature-dependent kinetic parameter, is remarkably similar to the distribution in the molecular dynamics trajectories.

  16. All-atom and coarse-grained molecular dynamics simulations of a membrane protein stabilizing polymer.

    PubMed

    Perlmutter, Jason D; Drasler, William J; Xie, Wangshen; Gao, Jiali; Popot, Jean-Luc; Sachs, Jonathan N

    2011-09-06

    Amphipathic polymers called amphipols (APols) have been developed as an alternative to detergents for stabilizing membrane proteins (MPs) in aqueous solutions. APols provide MPs with a particularly mild environment and, as a rule, keep them in a native functional state for longer periods than do detergents. Amphipol A8-35, a derivative of polyacrylate, is widely used and has been particularly well studied experimentally. In aqueous solutions, A8-35 molecules self-assemble into well-defined globular particles with a mass of ∼40 kDa and a R(g) of ∼2.4 nm. As a first step towards describing MP/A8-35 complexes by molecular dynamics (MD), we present three sets of simulations of the pure APol particle. First, we performed a series of all-atom MD (AAMD) simulations of the particle in solution, starting from an arbitrary initial configuration. Although AAMD simulations result in stable cohesive particles over a 45 ns simulation, the equilibration of the particle organization is limited. This motivated the use of coarse-grained MD (CGMD), allowing us to investigate processes on the microsecond time scale, including de novo particle assembly. We present a detailed description of the parametrization of the CGMD model from the AAMD simulations and a characterization of the resulting CGMD particles. Our third set of simulations utilizes reverse coarse-graining (rCG), through which we obtain all-atom coordinates from a CGMD simulation. This allows a higher-resolution characterization of a configuration determined by a long-timescale simulation. Excellent agreement is observed between MD models and experimental, small-angle neutron scattering data. The MD data provides new insight into the structure and dynamics of A8-35 particles, which is possibly relevant to the stabilizing effects of APols on MPs, as well as a starting point for modeling MP/A8-35 complexes.

  17. All-Atom and Coarse-Grained Molecular Dynamics Simulations of a Membrane Protein Stabilizing Polymer

    PubMed Central

    Perlmutter, Jason D.; Drasler, William J.; Xie, Wangshen; Gao, Jiali; Popot, Jean-Luc; Sachs, Jonathan N.

    2011-01-01

    Amphipathic polymers called amphipols (APols) have been developed as an alternative to detergents for stabilizing membrane proteins (MPs) in aqueous solutions. APols provide MPs with a particularly mild environment and, as a rule, keep them in a native and functional state for longer periods than detergents do. Amphipol A8-35, a derivative of polyacrylate, is widely used and has been particularly well studied experimentally. In aqueous solutions, A8-35 molecules self-assemble into well-defined globular particles, with a mass of ~40 kDa and a Rg of ~2.4 nm. As a first step towards describing MP/A8-35 complexes by molecular dynamics (MD), we present three sets of simulations of the pure APol particle. First, we performed a series of all-atom MD (AAMD) simulations of the particle in solution, starting from an arbitrary initial configuration. While AAMD simulations result in cohesive and stable particles over a 45-ns simulation, the equilibration of the particle organization is limited. This motivated the use of coarse-grained MD (CGMD), allowing us to investigate processes on the microsecond timescale, including de novo particle assembly. We present a detailed description of the parametrization of the CGMD model from the AAMD simulations, and a characterization of the resulting CGMD particles. Our third set of simulations utilizes reverse coarse-graining (rCG), through which we obtain all-atom coordinates from a CGMD simulation. This allows higher-resolution characterization of a configuration determined by a long-timescale simulation. An excellent agreement is observed between MD models and experimental, small angle neutron scattering data. The MD data provides new insights into the structure and dynamics of A8-35 particles, possibly relevant to the stabilizing effects of APols on MPs, as well as a starting point for modeling MP/A8-35 complexes. PMID:21806035

  18. Picosecond infrared laser-induced all-atom nonequilibrium molecular dynamics simulation of dissociation of viruses.

    PubMed

    Hoang Man, Viet; Van-Oanh, Nguyen-Thi; Derreumaux, Philippe; Li, Mai Suan; Roland, Christopher; Sagui, Celeste; Nguyen, Phuong H

    2016-04-28

    Since the discovery of the plant pathogen tobacco mosaic virus as the first viral entity in the late 1800s, viruses traditionally have been mainly thought of as pathogens for disease-resistances. However, viruses have recently been exploited as nanoplatforms with applications in biomedicine and materials science. To this aim, a large majority of current methods and tools have been developed to improve the physical stability of viral particles, which may be critical to the extreme physical or chemical conditions that viruses may encounter during purification, fabrication processes, storage and use. However, considerably fewer studies are devoted to developing efficient methods to degrade or recycle such enhanced stability biomaterials. With this in mind, we carry out all-atom nonequilibrium molecular dynamics simulation, inspired by the recently developed mid-infrared free-electron laser pulse technology, to dissociate viruses. Adopting the poliovirus as a representative example, we find that the primary step in the dissociation process is due to the strong resonance between the amide I vibrational modes of the virus and the tuned laser frequencies. This process is determined by a balance between the formation and dissociation of the protein shell, reflecting the highly plasticity of the virus. Furthermore, our method should provide a feasible approach to simulate viruses, which is otherwise too expensive for conventional equilibrium all-atom simulations of such very large systems. Our work shows a proof of concept which may open a new, efficient way to cleave or to recycle virus-based materials, provide an extremely valuable tool for elucidating mechanical aspects of viruses, and may well play an important role in future fighting against virus-related diseases.

  19. Charge-leveling and proper treatment of long-range electrostatics in all-atom molecular dynamics at constant pH

    NASA Astrophysics Data System (ADS)

    Wallace, Jason A.; Shen, Jana K.

    2012-11-01

    Recent development of constant pH molecular dynamics (CpHMD) methods has offered promise for adding pH-stat in molecular dynamics simulations. However, until now the working pH molecular dynamics (pHMD) implementations are dependent in part or whole on implicit-solvent models. Here we show that proper treatment of long-range electrostatics and maintaining charge neutrality of the system are critical for extending the continuous pHMD framework to the all-atom representation. The former is achieved here by adding forces to titration coordinates due to long-range electrostatics based on the generalized reaction field method, while the latter is made possible by a charge-leveling technique that couples proton titration with simultaneous ionization or neutralization of a co-ion in solution. We test the new method using the pH-replica-exchange CpHMD simulations of a series of aliphatic dicarboxylic acids with varying carbon chain length. The average absolute deviation from the experimental pKa values is merely 0.18 units. The results show that accounting for the forces due to extended electrostatics removes the large random noise in propagating titration coordinates, while maintaining charge neutrality of the system improves the accuracy in the calculated electrostatic interaction between ionizable sites. Thus, we believe that the way is paved for realizing pH-controlled all-atom molecular dynamics in the near future.

  20. Relationship between population of the fibril-prone conformation in the monomeric state and oligomer formation times of peptides: insights from all-atom simulations.

    PubMed

    Nam, Hoang Bao; Kouza, Maksim; Zung, Hoang; Li, Mai Suan

    2010-04-28

    Despite much progress in understanding the aggregation process of biomolecules, the factors that govern its rates have not been fully understood. This problem is of particular importance since many conformational diseases such as Alzheimer, Parkinson, and type-II diabetes are associated with the protein oligomerization. Having performed all-atom simulations with explicit water and various force fields for two short peptides KFFE and NNQQ, we show that their oligomer formation times are strongly correlated with the population of the fibril-prone conformation in the monomeric state. The larger the population the faster the aggregation process. Our result not only suggests that this quantity plays a key role in the self-assembly of polypeptide chains but also opens a new way to understand the fibrillogenesis of biomolecules at the monomeric level. The nature of oligomer ordering of NNQQ is studied in detail.

  1. Gay-Berne and electrostatic multipole based coarse-grain potential in implicit solvent

    NASA Astrophysics Data System (ADS)

    Wu, Johnny; Zhen, Xia; Shen, Hujun; Li, Guohui; Ren, Pengyu

    2011-10-01

    A general, transferable coarse-grain (CG) framework based on the Gay-Berne potential and electrostatic point multipole expansion is presented for polypeptide simulations. The solvent effect is described by the Generalized Kirkwood theory. The CG model is calibrated using the results of all-atom simulations of model compounds in solution. Instead of matching the overall effective forces produced by atomic models, the fundamental intermolecular forces such as electrostatic, repulsion-dispersion, and solvation are represented explicitly at a CG level. We demonstrate that the CG alanine dipeptide model is able to reproduce quantitatively the conformational energy of all-atom force fields in both gas and solution phases, including the electrostatic and solvation components. Replica exchange molecular dynamics and microsecond dynamic simulations of polyalanine of 5 and 12 residues reveal that the CG polyalanines fold into "alpha helix" and "beta sheet" structures. The 5-residue polyalanine displays a substantial increase in the "beta strand" fraction relative to the 12-residue polyalanine. The detailed conformational distribution is compared with those reported from recent all-atom simulations and experiments. The results suggest that the new coarse-graining approach presented in this study has the potential to offer both accuracy and efficiency for biomolecular modeling.

  2. Modeling alkane+perfluoroalkane interactions using all-atom potentials: Failure of the usual combining rules

    NASA Astrophysics Data System (ADS)

    Song, W.; Rossky, P. J.; Maroncelli, M.

    2003-11-01

    We have tested the ability of the OPLS-AA models (optimized potentials for liquid simulations) of alkanes and perfluoroalkanes recently developed by Jorgensen and co-workers to represent the unusual mixing behavior of alkane+perfluoroalkane systems. We find that these all-atom Lennard-Jones (6-12)+Coulomb representations, together with the usual Lorentz-Berthelot combining rules, fail to reproduce the weaker-than-anticipated interactions between these two classes of molecules. Systematic disagreements with experiment are found in the case of second pressure virial coefficients, gas solubilities, and liquid-liquid mixing properties. These discrepancies are not specific to the choice of OPLS-AA potentials, but are rather linked to the failure of the geometric mean combining rule for relating unlike atom interactions. In all cases examined, a reduction in the strength of cross H+F interactions by ˜25% relative to the geometric mean is required in order to achieve reasonable agreement with experiment. Several less commonly used combining rules were also examined. Although some of these rules are able to provide a reasonable description of the interactions among perfluoroalkane and alkane species, they fail to provide a consistent treatment when atoms other than C, H, and F are considered, as is necessary for modeling the interaction of the former molecules with rare-gas atoms.

  3. All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution

    SciTech Connect

    Andoh, Y.; Yoshii, N.; Yamada, A.; Kojima, H.; Mizutani, K.; Okazaki, S.; Fujimoto, K.; Nakagawa, A.; Nomoto, A.

    2014-10-28

    Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 10{sup 6} all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200 000) can leave the capsid and be replaced by water molecules from the outside in about 25 μs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

  4. All-atom molecular dynamics calculation study of entire poliovirus empty capsids in solution

    NASA Astrophysics Data System (ADS)

    Andoh, Y.; Yoshii, N.; Yamada, A.; Fujimoto, K.; Kojima, H.; Mizutani, K.; Nakagawa, A.; Nomoto, A.; Okazaki, S.

    2014-10-01

    Small viruses that belong, for example, to the Picornaviridae, such as poliovirus and foot-and-mouth disease virus, consist simply of capsid proteins and a single-stranded RNA (ssRNA) genome. The capsids are quite stable in solution to protect the genome from the environment. Here, based on long-time and large-scale 6.5 × 106 all-atom molecular dynamics calculations for the Mahoney strain of poliovirus, we show microscopic properties of the viral capsids at a molecular level. First, we found equilibrium rapid exchange of water molecules across the capsid. The exchange rate is so high that all water molecules inside the capsid (about 200 000) can leave the capsid and be replaced by water molecules from the outside in about 25 μs. This explains the capsid's tolerance to high pressures and deactivation by exsiccation. In contrast, the capsid did not exchange ions, at least within the present simulation time of 200 ns. This implies that the capsid can function, in principle, as a semipermeable membrane. We also found that, similar to the xylem of trees, the pressure of the solution inside the capsid without the genome was negative. This is caused by coulombic interaction of the solution inside the capsid with the capsid excess charges. The negative pressure may be compensated by positive osmotic pressure by the solution-soluble ssRNA and the counter ions introduced into it.

  5. Molecular jamming--the cystine slipknot mechanical clamp in all-atom simulations.

    PubMed

    Pepłowski, Lukasz; Sikora, Mateusz; Nowak, Wiesław; Cieplak, Marek

    2011-02-28

    A recent survey of 17 134 proteins has identified a new class of proteins which are expected to yield stretching induced force peaks in the range of 1 nN. Such high force peaks should be due to forcing of a slip-loop through a cystine ring, i.e., by generating a cystine slipknot. The survey has been performed in a simple coarse grained model. Here, we perform all-atom steered molecular dynamics simulations on 15 cystine knot proteins and determine their resistance to stretching. In agreement with previous studies within a coarse grained structure based model, the level of resistance is found to be substantially higher than in proteins in which the mechanical clamp operates through shear. The large stretching forces arise through formation of the cystine slipknot mechanical clamp and the resulting steric jamming. We elucidate the workings of such a clamp in an atomic detail. We also study the behavior of five top strength proteins with the shear-based mechanostability in which no jamming is involved. We show that in the atomic model, the jamming state is relieved by moving one amino acid at a time and there is a choice in the selection of the amino acid that advances the first. In contrast, the coarse grained model also allows for a simultaneous passage of two amino acids.

  6. The folding thermodynamics and kinetics of crambin using an all-atom Monte Carlo simulation.

    PubMed

    Shimada, J; Kussell, E L; Shakhnovich, E I

    2001-04-20

    We present a novel Monte Carlo simulation of protein folding, in which all heavy atoms are represented as interacting hard spheres. This model includes all degrees of freedom relevant to folding, all side-chain and backbone torsions, and uses a Go potential. In this study, we focus on the 46 residue alpha/beta protein crambin and two of its structural components, the helix and helix hairpin. For a wide range of temperatures, we recorded multiple folding events of these three structures from random coils to native conformations that differ by less than 1 A C(alpha) dRMS from their crystal structure coordinates. The thermodynamics and kinetic mechanism of the helix-coil transition obtained from our simulation shows excellent agreement with currently available experimental and molecular dynamics data. Based on insights obtained from folding its smaller structural components, a possible folding mechanism for crambin is proposed. We observed that the folding occurs via a cooperative, first order-like process, and that many folding pathways to the native state exist. One particular sequence of events constitutes a "fast-folding" pathway where kinetic traps are avoided. At very low temperatures, a kinetic trap arising from the incorrect packing of side-chains was observed. These results demonstrate that folding to the native state can be observed in a reasonable amount of time on desktop computers even when an all-atom representation is used, provided the energetics sufficiently stabilize the native state.

  7. Refined OPLS all-atom force field for saturated phosphatidylcholine bilayers at full hydration.

    PubMed

    Maciejewski, Arkadiusz; Pasenkiewicz-Gierula, Marta; Cramariuc, Oana; Vattulainen, Ilpo; Rog, Tomasz

    2014-05-01

    We report parametrization of dipalmitoyl-phosphatidylcholine (DPPC) in the framework of the Optimized Parameters for Liquid Simulations all-atom (OPLS-AA) force field. We chose DPPC as it is one of the most studied phospholipid species and thus has plenty of experimental data necessary for model validation, and it is also one of the highly important and abundant lipid types, e.g., in lung surfactant. Overall, PCs have not been previously parametrized in the OPLS-AA force field; thus, there is a need to derive its bonding and nonbonding parameters for both the polar and nonpolar parts of the molecule. In the present study, we determined the parameters for torsion angles in the phosphatidylcholine and glycerol moieties and in the acyl chains, as well the partial atomic charges. In these calculations, we used three methods: (1) Hartree-Fock (HF), (2) second order Møller-Plesset perturbation theory (MP2), and (3) density functional theory (DFT). We also tested the effect of the polar environment by using the polarizable continuum model (PCM), and for acyl chains the van der Waals parameters were also adjusted. In effect, six parameter sets were generated and tested on a DPPC bilayer. Out of these six sets, only one was found to be able to satisfactorily reproduce experimental data for the lipid bilayer. The successful DPPC model was obtained from MP2 calculations in an implicit polar environment (PCM).

  8. Refinement of protein structure homology models via long, all-atom molecular dynamics simulations.

    PubMed

    Raval, Alpan; Piana, Stefano; Eastwood, Michael P; Dror, Ron O; Shaw, David E

    2012-08-01

    Accurate computational prediction of protein structure represents a longstanding challenge in molecular biology and structure-based drug design. Although homology modeling techniques are widely used to produce low-resolution models, refining these models to high resolution has proven difficult. With long enough simulations and sufficiently accurate force fields, molecular dynamics (MD) simulations should in principle allow such refinement, but efforts to refine homology models using MD have for the most part yielded disappointing results. It has thus far been unclear whether MD-based refinement is limited primarily by accessible simulation timescales, force field accuracy, or both. Here, we examine MD as a technique for homology model refinement using all-atom simulations, each at least 100 μs long-more than 100 times longer than previous refinement simulations-and a physics-based force field that was recently shown to successfully fold a structurally diverse set of fast-folding proteins. In MD simulations of 24 proteins chosen from the refinement category of recent Critical Assessment of Structure Prediction (CASP) experiments, we find that in most cases, simulations initiated from homology models drift away from the native structure. Comparison with simulations initiated from the native structure suggests that force field accuracy is the primary factor limiting MD-based refinement. This problem can be mitigated to some extent by restricting sampling to the neighborhood of the initial model, leading to structural improvement that, while limited, is roughly comparable to the leading alternative methods.

  9. ALMOST: an all atom molecular simulation toolkit for protein structure determination.

    PubMed

    Fu, Biao; Sahakyan, Aleksandr B; Camilloni, Carlo; Tartaglia, Gian Gaetano; Paci, Emanuele; Caflisch, Amedeo; Vendruscolo, Michele; Cavalli, Andrea

    2014-05-30

    Almost (all atom molecular simulation toolkit) is an open source computational package for structure determination and analysis of complex molecular systems including proteins, and nucleic acids. Almost has been designed with two primary goals: to provide tools for molecular structure determination using various types of experimental measurements as conformational restraints, and to provide methods for the analysis and assessment of structural and dynamical properties of complex molecular systems. The methods incorporated in Almost include the determination of structural and dynamical features of proteins using distance restraints derived from nuclear Overhauser effect measurements, orientational restraints obtained from residual dipolar couplings and the structural restraints from chemical shifts. Here, we present the first public release of Almost, highlight the key aspects of its computational design and discuss the main features currently implemented. Almost is available for the most common Unix-based operating systems, including Linux and Mac OS X. Almost is distributed free of charge under the GNU Public License, and is available both as a source code and as a binary executable from the project web site at http://www.open-almost.org. Interested users can follow and contribute to the further development of Almost on http://sourceforge.net/projects/almost.

  10. A Real-Time All-Atom Structural Search Engine for Proteins

    PubMed Central

    Gonzalez, Gabriel; Hannigan, Brett; DeGrado, William F.

    2014-01-01

    Protein designers use a wide variety of software tools for de novo design, yet their repertoire still lacks a fast and interactive all-atom search engine. To solve this, we have built the Suns program: a real-time, atomic search engine integrated into the PyMOL molecular visualization system. Users build atomic-level structural search queries within PyMOL and receive a stream of search results aligned to their query within a few seconds. This instant feedback cycle enables a new “designability”-inspired approach to protein design where the designer searches for and interactively incorporates native-like fragments from proven protein structures. We demonstrate the use of Suns to interactively build protein motifs, tertiary interactions, and to identify scaffolds compatible with hot-spot residues. The official web site and installer are located at http://www.degradolab.org/suns/ and the source code is hosted at https://github.com/godotgildor/Suns (PyMOL plugin, BSD license), https://github.com/Gabriel439/suns-cmd (command line client, BSD license), and https://github.com/Gabriel439/suns-search (search engine server, GPLv2 license). PMID:25079944

  11. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids

    PubMed Central

    Davis, Ian W.; Leaver-Fay, Andrew; Chen, Vincent B.; Block, Jeremy N.; Kapral, Gary J.; Wang, Xueyi; Murray, Laura W.; Arendall, W. Bryan; Snoeyink, Jack; Richardson, Jane S.; Richardson, David C.

    2007-01-01

    MolProbity is a general-purpose web server offering quality validation for 3D structures of proteins, nucleic acids and complexes. It provides detailed all-atom contact analysis of any steric problems within the molecules as well as updated dihedral-angle diagnostics, and it can calculate and display the H-bond and van der Waals contacts in the interfaces between components. An integral step in the process is the addition and full optimization of all hydrogen atoms, both polar and nonpolar. New analysis functions have been added for RNA, for interfaces, and for NMR ensembles. Additionally, both the web site and major component programs have been rewritten to improve speed, convenience, clarity and integration with other resources. MolProbity results are reported in multiple forms: as overall numeric scores, as lists or charts of local problems, as downloadable PDB and graphics files, and most notably as informative, manipulable 3D kinemage graphics shown online in the KiNG viewer. This service is available free to all users at http://molprobity.biochem.duke.edu. PMID:17452350

  12. A real-time all-atom structural search engine for proteins.

    PubMed

    Gonzalez, Gabriel; Hannigan, Brett; DeGrado, William F

    2014-07-01

    Protein designers use a wide variety of software tools for de novo design, yet their repertoire still lacks a fast and interactive all-atom search engine. To solve this, we have built the Suns program: a real-time, atomic search engine integrated into the PyMOL molecular visualization system. Users build atomic-level structural search queries within PyMOL and receive a stream of search results aligned to their query within a few seconds. This instant feedback cycle enables a new "designability"-inspired approach to protein design where the designer searches for and interactively incorporates native-like fragments from proven protein structures. We demonstrate the use of Suns to interactively build protein motifs, tertiary interactions, and to identify scaffolds compatible with hot-spot residues. The official web site and installer are located at http://www.degradolab.org/suns/ and the source code is hosted at https://github.com/godotgildor/Suns (PyMOL plugin, BSD license), https://github.com/Gabriel439/suns-cmd (command line client, BSD license), and https://github.com/Gabriel439/suns-search (search engine server, GPLv2 license).

  13. Reparameterization of all-atom dipalmitoylphosphatidylcholine lipid parameters enables simulation of fluid bilayers at zero tension.

    PubMed

    Sonne, Jacob; Jensen, Morten Ø; Hansen, Flemming Y; Hemmingsen, Lars; Peters, Günther H

    2007-06-15

    Molecular dynamics simulations of dipalmitoylphosphatidylcholine (DPPC) lipid bilayers using the CHARMM27 force field in the tensionless isothermal-isobaric (NPT) ensemble give highly ordered, gel-like bilayers with an area per lipid of approximately 48 A(2). To obtain fluid (L(alpha)) phase properties of DPPC bilayers represented by the CHARMM energy function in this ensemble, we reparameterized the atomic partial charges in the lipid headgroup and upper parts of the acyl chains. The new charges were determined from the electron structure using both the Mulliken method and the restricted electrostatic potential fitting method. We tested the derived charges in molecular dynamics simulations of a fully hydrated DPPC bilayer. Only the simulation with the new restricted electrostatic potential charges shows significant improvements compared with simulations using the original CHARMM27 force field resulting in an area per lipid of 60.4 +/- 0.1 A(2). Compared to the 48 A(2), the new value of 60.4 A(2) is in fair agreement with the experimental value of 64 A(2). In addition, the simulated order parameter profile and electron density profile are in satisfactory agreement with experimental data. Thus, the biologically more interesting fluid phase of DPPC bilayers can now be simulated in all-atom simulations in the NPT ensemble by employing our modified CHARMM27 force field.

  14. All-atom model for stabilization of alpha-helical structure in peptides by hydrocarbon staples.

    PubMed

    Kutchukian, Peter S; Yang, Jae Shick; Verdine, Gregory L; Shakhnovich, Eugene I

    2009-04-08

    Recent work has shown that the incorporation of an all-hydrocarbon "staple" into peptides can greatly increase their alpha-helix propensity, leading to an improvement in pharmaceutical properties such as proteolytic stability, receptor affinity, and cell permeability. Stapled peptides thus show promise as a new class of drugs capable of accessing intractable targets such as those that engage in intracellular protein-protein interactions. The extent of alpha-helix stabilization provided by stapling has proven to be substantially context dependent, requiring cumbersome screening to identify the optimal site for staple incorporation. In certain cases, a staple encompassing one turn of the helix (attached at residues i and i+4) furnishes greater helix stabilization than one encompassing two turns (i,i+7 staple), which runs counter to expectation based on polymer theory. These findings highlight the need for a more thorough understanding of the forces that underlie helix stabilization by hydrocarbon staples. Here we report all-atom Monte Carlo folding simulations comparing unmodified peptides derived from RNase A and BID BH3 with various i,i+4 and i,i+7 stapled versions thereof. The results of these simulations were found to be in quantitative agreement with experimentally determined helix propensities. We also discovered that staples can stabilize quasi-stable decoy conformations, and that the removal of these states plays a major role in determining the helix stability of stapled peptides. Finally, we critically investigate why our method works, exposing the underlying physical forces that stabilize stapled peptides.

  15. Protein model refinement using an optimized physics-based all-atom force field.

    PubMed

    Jagielska, Anna; Wroblewska, Liliana; Skolnick, Jeffrey

    2008-06-17

    One of the greatest challenges in protein structure prediction is the refinement of low-resolution predicted models to high-resolution structures that are close to the native state. Although contemporary structure prediction methods can assemble the correct topology for a large fraction of protein domains, such approximate models are often not of the resolution required for many important applications, including studies of reaction mechanisms and virtual ligand screening. Thus, the development of a method that could bring those structures closer to the native state is of great importance. We recently optimized the relative weights of the components of the Amber ff03 potential on a large set of decoy structures to create a funnel-shaped energy landscape with the native structure at the global minimum. Such an energy function might be able to drive proteins toward their native structure. In this work, for a test set of 47 proteins, with 100 decoy structures per protein that have a range of structural similarities to the native state, we demonstrate that our optimized potential can drive protein models closer to their native structure. Comparing the lowest-energy structure from each trajectory with the starting decoy, structural improvement is seen for 70% of the models on average. The ability to do such systematic structural refinements by using a physics-based all-atom potential represents a promising approach to high-resolution structure prediction.

  16. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids.

    PubMed

    Davis, Ian W; Leaver-Fay, Andrew; Chen, Vincent B; Block, Jeremy N; Kapral, Gary J; Wang, Xueyi; Murray, Laura W; Arendall, W Bryan; Snoeyink, Jack; Richardson, Jane S; Richardson, David C

    2007-07-01

    MolProbity is a general-purpose web server offering quality validation for 3D structures of proteins, nucleic acids and complexes. It provides detailed all-atom contact analysis of any steric problems within the molecules as well as updated dihedral-angle diagnostics, and it can calculate and display the H-bond and van der Waals contacts in the interfaces between components. An integral step in the process is the addition and full optimization of all hydrogen atoms, both polar and nonpolar. New analysis functions have been added for RNA, for interfaces, and for NMR ensembles. Additionally, both the web site and major component programs have been rewritten to improve speed, convenience, clarity and integration with other resources. MolProbity results are reported in multiple forms: as overall numeric scores, as lists or charts of local problems, as downloadable PDB and graphics files, and most notably as informative, manipulable 3D kinemage graphics shown online in the KiNG viewer. This service is available free to all users at http://molprobity.biochem.duke.edu.

  17. High-throughput all-atom molecular dynamics simulations using distributed computing.

    PubMed

    Buch, I; Harvey, M J; Giorgino, T; Anderson, D P; De Fabritiis, G

    2010-03-22

    Although molecular dynamics simulation methods are useful in the modeling of macromolecular systems, they remain computationally expensive, with production work requiring costly high-performance computing (HPC) resources. We review recent innovations in accelerating molecular dynamics on graphics processing units (GPUs), and we describe GPUGRID, a volunteer computing project that uses the GPU resources of nondedicated desktop and workstation computers. In particular, we demonstrate the capability of simulating thousands of all-atom molecular trajectories generated at an average of 20 ns/day each (for systems of approximately 30 000-80 000 atoms). In conjunction with a potential of mean force (PMF) protocol for computing binding free energies, we demonstrate the use of GPUGRID in the computation of accurate binding affinities of the Src SH2 domain/pYEEI ligand complex by reconstructing the PMF over 373 umbrella sampling windows of 55 ns each (20.5 mus of total data). We obtain a standard free energy of binding of -8.7 +/- 0.4 kcal/mol within 0.7 kcal/mol from experimental results. This infrastructure will provide the basis for a robust system for high-throughput accurate binding affinity prediction.

  18. All-atom 3D structure prediction of transmembrane β-barrel proteins from sequences

    PubMed Central

    Hayat, Sikander; Sander, Chris; Marks, Debora S.

    2015-01-01

    Transmembrane β-barrels (TMBs) carry out major functions in substrate transport and protein biogenesis but experimental determination of their 3D structure is challenging. Encouraged by successful de novo 3D structure prediction of globular and α-helical membrane proteins from sequence alignments alone, we developed an approach to predict the 3D structure of TMBs. The approach combines the maximum-entropy evolutionary coupling method for predicting residue contacts (EVfold) with a machine-learning approach (boctopus2) for predicting β-strands in the barrel. In a blinded test for 19 TMB proteins of known structure that have a sufficient number of diverse homologous sequences available, this combined method (EVfold_bb) predicts hydrogen-bonded residue pairs between adjacent β-strands at an accuracy of ∼70%. This accuracy is sufficient for the generation of all-atom 3D models. In the transmembrane barrel region, the average 3D structure accuracy [template-modeling (TM) score] of top-ranked models is 0.54 (ranging from 0.36 to 0.85), with a higher (44%) number of residue pairs in correct strand–strand registration than in earlier methods (18%). Although the nonbarrel regions are predicted less accurately overall, the evolutionary couplings identify some highly constrained loop residues and, for FecA protein, the barrel including the structure of a plug domain can be accurately modeled (TM score = 0.68). Lower prediction accuracy tends to be associated with insufficient sequence information and we therefore expect increasing numbers of β-barrel families to become accessible to accurate 3D structure prediction as the number of available sequences increases. PMID:25858953

  19. Effect of Calcium and Magnesium on Phosphatidylserine Membranes: Experiments and All-Atomic Simulations

    PubMed Central

    Martín-Molina, Alberto; Rodríguez-Beas, César; Faraudo, Jordi

    2012-01-01

    It is known that phosphatidylserine (PS−) lipids have a very similar affinity for Ca2+ and Mg2+ cations, as revealed by electrokinetic and stability experiments. However, despite this similar affinity, experimental evidence shows that the presence of Ca2+ or Mg2+ induces very different aggregation behavior for PS− liposomes as characterized by their fractal dimensions. Also, turbidity measurements confirm substantial differences in aggregation behavior depending on the presence of Ca2+ or Mg2+ cations. These puzzling results suggest that although these two cations have a similar affinity for PS− lipids, they induce substantial structural differences in lipid bilayers containing each of these cations. In other words, these cations have strong ion-specific effects on the structure of PS− membranes. This interpretation is supported by all-atomic molecular-dynamics simulations showing that Ca2+ and Mg2+ cations have different binding sites and induce different membrane hydration. We show that although both ions are incorporated deep into the hydrophilic region of the membrane, they have different positions and configurations at the membrane. Absorbed Ca2+ cations present a peak at a distance ∼2 nm from the center of the lipid bilayer, and their most probable binding configuration involves two oxygen atoms from each of the charged moieties of the PS molecule (phosphate and carboxyl groups). In contrast, the distribution of absorbed Mg2+ cations has two different peaks, located a few angstroms before and after the Ca2+ peak. The most probable configurations (corresponding to these two peaks) involve binding to two oxygen atoms from carboxyl groups (the most superficial binding peak) or two oxygen atoms from phosphate groups (the most internal peak). Moreover, simulations also show differences in the hydration structure of the membrane: we obtained a hydration of 7.5 and 9 water molecules per lipid in simulations with Ca2+ and Mg2+, respectively. PMID:22824273

  20. Effect of calcium and magnesium on phosphatidylserine membranes: experiments and all-atomic simulations.

    PubMed

    Martín-Molina, Alberto; Rodríguez-Beas, César; Faraudo, Jordi

    2012-05-02

    It is known that phosphatidylserine (PS(-)) lipids have a very similar affinity for Ca(2+) and Mg(2+) cations, as revealed by electrokinetic and stability experiments. However, despite this similar affinity, experimental evidence shows that the presence of Ca(2+) or Mg(2+) induces very different aggregation behavior for PS(-) liposomes as characterized by their fractal dimensions. Also, turbidity measurements confirm substantial differences in aggregation behavior depending on the presence of Ca(2+) or Mg(2+) cations. These puzzling results suggest that although these two cations have a similar affinity for PS(-) lipids, they induce substantial structural differences in lipid bilayers containing each of these cations. In other words, these cations have strong ion-specific effects on the structure of PS(-) membranes. This interpretation is supported by all-atomic molecular-dynamics simulations showing that Ca(2+) and Mg(2+) cations have different binding sites and induce different membrane hydration. We show that although both ions are incorporated deep into the hydrophilic region of the membrane, they have different positions and configurations at the membrane. Absorbed Ca(2+) cations present a peak at a distance ~2 nm from the center of the lipid bilayer, and their most probable binding configuration involves two oxygen atoms from each of the charged moieties of the PS molecule (phosphate and carboxyl groups). In contrast, the distribution of absorbed Mg(2+) cations has two different peaks, located a few angstroms before and after the Ca(2+) peak. The most probable configurations (corresponding to these two peaks) involve binding to two oxygen atoms from carboxyl groups (the most superficial binding peak) or two oxygen atoms from phosphate groups (the most internal peak). Moreover, simulations also show differences in the hydration structure of the membrane: we obtained a hydration of 7.5 and 9 water molecules per lipid in simulations with Ca(2+) and Mg(2

  1. MolProbity: all-atom structure validation for macromolecular crystallography.

    PubMed

    Chen, Vincent B; Arendall, W Bryan; Headd, Jeffrey J; Keedy, Daniel A; Immormino, Robert M; Kapral, Gary J; Murray, Laura W; Richardson, Jane S; Richardson, David C

    2010-01-01

    MolProbity is a structure-validation web service that provides broad-spectrum solidly based evaluation of model quality at both the global and local levels for both proteins and nucleic acids. It relies heavily on the power and sensitivity provided by optimized hydrogen placement and all-atom contact analysis, complemented by updated versions of covalent-geometry and torsion-angle criteria. Some of the local corrections can be performed automatically in MolProbity and all of the diagnostics are presented in chart and graphical forms that help guide manual rebuilding. X-ray crystallography provides a wealth of biologically important molecular data in the form of atomic three-dimensional structures of proteins, nucleic acids and increasingly large complexes in multiple forms and states. Advances in automation, in everything from crystallization to data collection to phasing to model building to refinement, have made solving a structure using crystallography easier than ever. However, despite these improvements, local errors that can affect biological interpretation are widespread at low resolution and even high-resolution structures nearly all contain at least a few local errors such as Ramachandran outliers, flipped branched protein side chains and incorrect sugar puckers. It is critical both for the crystallographer and for the end user that there are easy and reliable methods to diagnose and correct these sorts of errors in structures. MolProbity is the authors' contribution to helping solve this problem and this article reviews its general capabilities, reports on recent enhancements and usage, and presents evidence that the resulting improvements are now beneficially affecting the global database.

  2. Free-energy function based on an all-atom model for proteins.

    PubMed

    Yoshidome, Takashi; Oda, Koji; Harano, Yuichi; Roth, Roland; Sugita, Yuji; Ikeguchi, Mitsunori; Kinoshita, Masahiro

    2009-12-01

    We have developed a free-energy function based on an all-atom model for proteins. It comprises two components, the hydration entropy (HE) and the total dehydration penalty (TDP). Upon a transition to a more compact structure, the number of accessible configurations arising from the translational displacement of water molecules in the system increases, leading to a water-entropy gain. To fully account for this effect, the HE is calculated using a statistical-mechanical theory applied to a molecular model for water. The TDP corresponds to the sum of the hydration energy and the protein intramolecular energy when a fully extended structure, which possesses the maximum number of hydrogen bonds with water molecules and no intramolecular hydrogen bonds, is chosen as the standard one. When a donor and an acceptor (e.g., N and O, respectively) are buried in the interior after the break of hydrogen bonds with water molecules, if they form an intramolecular hydrogen bond, no penalty is imposed. When a donor or an acceptor is buried with no intramolecular hydrogen bond formed, an energetic penalty is imposed. We examine all the donors and acceptors for backbone-backbone, backbone-side chain, and side chain-side chain intramolecular hydrogen bonds and calculate the TDP. Our free-energy function has been tested for three different decoy sets. It is better than any other physics-based or knowledge-based potential function in terms of the accuracy in discriminating the native fold from misfolded decoys and the achievement of high Z-scores.

  3. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics.

    PubMed

    Zhao, Gongpu; Perilla, Juan R; Yufenyuy, Ernest L; Meng, Xin; Chen, Bo; Ning, Jiying; Ahn, Jinwoo; Gronenborn, Angela M; Schulten, Klaus; Aiken, Christopher; Zhang, Peijun

    2013-05-30

    Retroviral capsid proteins are conserved structurally but assemble into different morphologies. The mature human immunodeficiency virus-1 (HIV-1) capsid is best described by a 'fullerene cone' model, in which hexamers of the capsid protein are linked to form a hexagonal surface lattice that is closed by incorporating 12 capsid-protein pentamers. HIV-1 capsid protein contains an amino-terminal domain (NTD) comprising seven α-helices and a β-hairpin, a carboxy-terminal domain (CTD) comprising four α-helices, and a flexible linker with a 310-helix connecting the two structural domains. Structures of the capsid-protein assembly units have been determined by X-ray crystallography; however, structural information regarding the assembled capsid and the contacts between the assembly units is incomplete. Here we report the cryo-electron microscopy structure of a tubular HIV-1 capsid-protein assembly at 8 Å resolution and the three-dimensional structure of a native HIV-1 core by cryo-electron tomography. The structure of the tubular assembly shows, at the three-fold interface, a three-helix bundle with critical hydrophobic interactions. Mutagenesis studies confirm that hydrophobic residues in the centre of the three-helix bundle are crucial for capsid assembly and stability, and for viral infectivity. The cryo-electron-microscopy structures enable modelling by large-scale molecular dynamics simulation, resulting in all-atom models for the hexamer-of-hexamer and pentamer-of-hexamer elements as well as for the entire capsid. Incorporation of pentamers results in closer trimer contacts and induces acute surface curvature. The complete atomic HIV-1 capsid model provides a platform for further studies of capsid function and for targeted pharmacological intervention.

  4. All-atom 3D structure prediction of transmembrane β-barrel proteins from sequences.

    PubMed

    Hayat, Sikander; Sander, Chris; Marks, Debora S; Elofsson, Arne

    2015-04-28

    Transmembrane β-barrels (TMBs) carry out major functions in substrate transport and protein biogenesis but experimental determination of their 3D structure is challenging. Encouraged by successful de novo 3D structure prediction of globular and α-helical membrane proteins from sequence alignments alone, we developed an approach to predict the 3D structure of TMBs. The approach combines the maximum-entropy evolutionary coupling method for predicting residue contacts (EVfold) with a machine-learning approach (boctopus2) for predicting β-strands in the barrel. In a blinded test for 19 TMB proteins of known structure that have a sufficient number of diverse homologous sequences available, this combined method (EVfold_bb) predicts hydrogen-bonded residue pairs between adjacent β-strands at an accuracy of ∼70%. This accuracy is sufficient for the generation of all-atom 3D models. In the transmembrane barrel region, the average 3D structure accuracy [template-modeling (TM) score] of top-ranked models is 0.54 (ranging from 0.36 to 0.85), with a higher (44%) number of residue pairs in correct strand-strand registration than in earlier methods (18%). Although the nonbarrel regions are predicted less accurately overall, the evolutionary couplings identify some highly constrained loop residues and, for FecA protein, the barrel including the structure of a plug domain can be accurately modeled (TM score = 0.68). Lower prediction accuracy tends to be associated with insufficient sequence information and we therefore expect increasing numbers of β-barrel families to become accessible to accurate 3D structure prediction as the number of available sequences increases.

  5. Molecular dynamics simulation of protein adsorption at fluid interfaces: a comparison of all-atom and coarse-grained models.

    PubMed

    Euston, Stephen R

    2010-10-11

    The adsorption of LTP at the decane-water interface was modeled using all-atom and coarse-grained (CG) molecular dynamics simulations. The CG model (300 ns simulation, 1200 ns scaled time) generates equilibrium adsorbed conformations in about 12 h, whereas the equivalent 1200 ns simulation would take about 300 days for the all-atom model. In both models the LTP molecule adsorbs with α-helical regions parallel to the interface with an average tilt angle normal to the interface of 73° for the all-atom model and 62° for the CG model. In the all-atom model, the secondary structure of the LTP is conserved upon adsorption. A considerable proportion of the N-terminal loop of LTP can be found in the decane phase for the all-atom model, whereas in the CG model the protein only penetrates as far as the mixed water-decane interfacial region. This difference may arise due to the different schemes used to parametrize force field parameters in the two models.

  6. Interfaces and hydrophobic interactions in receptor-ligand systems: A level-set variational implicit solvent approach.

    PubMed

    Cheng, Li-Tien; Wang, Zhongming; Setny, Piotr; Dzubiella, Joachim; Li, Bo; McCammon, J Andrew

    2009-10-14

    A model nanometer-sized hydrophobic receptor-ligand system in aqueous solution is studied by the recently developed level-set variational implicit solvent model (VISM). This approach is compared to all-atom computer simulations. The simulations reveal complex hydration effects within the (concave) receptor pocket, sensitive to the distance of the (convex) approaching ligand. The ligand induces and controls an intermittent switching between dry and wet states of the hosting pocket, which determines the range and magnitude of the pocket-ligand attraction. In the level-set VISM, a geometric free-energy functional of all possible solute-solvent interfaces coupled to the local dispersion potential is minimized numerically. This approach captures the distinct metastable states that correspond to topologically different solute-solvent interfaces, and thereby reproduces the bimodal hydration behavior observed in the all-atom simulation. Geometrical singularities formed during the interface relaxation are found to contribute significantly to the energy barrier between different metastable states. While the hydration phenomena can thus be explained by capillary effects, the explicit inclusion of dispersion and curvature corrections seems to be essential for a quantitative description of hydrophobically confined systems on nanoscales. This study may shed more light onto the tight connection between geometric and energetic aspects of biomolecular hydration and may represent a valuable step toward the proper interpretation of experimental receptor-ligand binding rates.

  7. Automatic protein design with all atom force-fields by exact and heuristic optimization.

    PubMed

    Wernisch, L; Hery, S; Wodak, S J

    2000-08-18

    A fully automatic procedure for predicting the amino acid sequences compatible with a given target structure is described. It is based on the CHARMM package, and uses an all atom force-field and rotamer libraries to describe and evaluate side-chain types and conformations. Sequences are ranked by a quantity akin to the free energy of folding, which incorporates hydration effects. Exact (Branch and Bound) and heuristic optimisation procedures are used to identifying highly scoring sequences from an astronomical number of possibilities. These sequences include the minimum free energy sequence, as well as all amino acid sequences whose free energy lies within a specified window from the minimum. Several applications of our procedure are illustrated. Prediction of side-chain conformations for a set of ten proteins yields results comparable to those of established side-chain placement programs. Applications to sequence optimisation comprise the re-design of the protein cores of c-Crk SH3 domain, the B1 domain of protein G and Ubiquitin, and of surface residues of the SH3 domain. In all calculations, no restrictions are imposed on the amino acid composition and identical parameter settings are used for core and surface residues. The best scoring sequences for the protein cores are virtually identical to wild-type. They feature no more than one to three mutations in a total of 11-16 variable positions. Tests suggest that this is due to the balance between various contributions in the force-field rather than to overwhelming influence from packing constraints. The effectiveness of our force-field is further supported by the sequence predictions for surface residues of the SH3 domain. More mutations are predicted than in the core, seemingly in order to optimise the network of complementary interactions between polar and charged groups. This appears to be an important energetic requirement in absence of the partner molecules with which the SH3 domain interacts, which were not

  8. Benchmarking Implicit Solvent Folding Simulations of the Amyloid β(10–35) Fragment

    PubMed Central

    Kent, Andrew; Jha, Abhishek K; Fitzgerald, James E; Freed, Karl F

    2009-01-01

    A pathogenetic feature of Alzhemier disease is the aggregation of monomeric β-amyloid proteins (Aβ) to form oligomers. Usually these oligomers of long peptides aggregate on time scales of microseconds or longer, making computational studies using atomistic molecular dynamics models prohibitively expensive and making it essential to develop computational models that are cheaper and at the same time faithful to physical features of the process. We benchmark the ability of our implicit solvent model to describe equilibrium and dynamic properties of monomeric Aβ(10–35) using all-atom Langevin dynamics (LD) simulations since Aβ(10–35) is the only fragment whose monomeric properties have been measured. The accuracy of the implicit solvent model is tested by comparing its predictions with experiment and with those from a new explicit water MD simulation, (performed using CHARMM and the TIP3P water model) which is ~200 times slower than the implicit water simulations. The dependence on force field is investigated by running multiple trajectories for Aβ(10–35) using the CHARMM, OPLS-aal, and GS-AMBER94 force fields, while the convergence to equilibrium is tested for each force field by beginning separate trajectories from the native NMR structure, a completely stretched structure, and from unfolded initial structures. The NMR order parameter S2 is computed for each trajectory and is compared with experimental data to assess the best choice for treating aggregates of Aβ. The results vary significantly with force field. Explicit and implicit solvent simulations using the CHARMM force fields display excellent agreement with each other and once again support the accuracy of the implicit solvent model. Aβ(10–35) exhibits great flexibility, consistent with experiment data for the monomer in solution, while maintaining a general strand-loop-strand motif with a solvent exposed hydrophobic patch that is believed to be important for aggregation. Finally, equilibration

  9. Transition state of a SH3 domain detected with principle component analysis and a charge-neutralized all-atom protein model.

    PubMed

    Mitomo, Daisuke; Nakamura, Hironori K; Ikeda, Kazuyoshi; Yamagishi, Akihiko; Higo, Junichi

    2006-09-01

    The src SH3 domain has been known to be a two-state folder near room temperature. However, in a previous study with an all-atom model simulation near room temperature, the transition state of this protein was not successfully detected on a free-energy profile using two axes: the radius of gyration (R(g)) and native contact reproduction ratio (Q value). In this study, we focused on an atom packing effect to characterize the transition state and tried another analysis to detect it. To explore the atom packing effect more efficiently, we introduced a charge-neutralized all-atom model, where all of the atoms in the protein and water molecules were treated explicitly, but their partial atomic charges were set to zero. Ten molecular dynamics simulations were performed starting from the native structure at 300 K, where the simulation length of each run was 90 ns, and the protein unfolded in all runs. The integrated trajectories (10 x 90 = 900 ns) were analyzed by a principal component analysis (PCA) and showed a clear free-energy barrier between folded- and unfolded-state conformational clusters in a conformational space generated by PCA. There were segments that largely deformed when the conformation passed through the free-energy barrier. These segments correlated well with the structural core regions characterized by large phi-values, and the atom-packing changes correlated with the conformational deformations. Interestingly, using the same simulation data, no significant barrier was found in a free-energy profile using the R(g) and Q values for the coordinate axes. These results suggest that the atom packing effect may be one of the most important determinants of the transition state.

  10. All-Atom Internal Coordinate Mechanics (ICM) Force Field for Hexopyranoses and Glycoproteins.

    PubMed

    Arnautova, Yelena A; Abagyan, Ruben; Totrov, Maxim

    2015-05-12

    We present an extension of the all-atom internal-coordinate force field, ICMFF, that allows for simulation of heterogeneous systems including hexopyranose saccharides and glycan chains in addition to proteins. A library of standard glycan geometries containing α- and β-anomers of the most common hexapyranoses, i.e., d-galactose, d-glucose, d-mannose, d-xylose, l-fucose, N-acetylglucosamine, N-acetylgalactosamine, sialic, and glucuronic acids, is created based on the analysis of the saccharide structures reported in the Cambridge Structural Database. The new force field parameters include molecular electrostatic potential-derived partial atomic charges and the torsional parameters derived from quantum mechanical data for a collection of minimal molecular fragments and related molecules. The ϕ/ψ torsional parameters for different types of glycosidic linkages are developed using model compounds containing the key atoms in the full carbohydrates, i.e., glycosidic-linked tetrahydropyran-cyclohexane dimers. Target data for parameter optimization include two-dimensional energy surfaces corresponding to the ϕ/ψ glycosidic dihedral angles in the disaccharide analogues, as determined by quantum mechanical MP2/6-31G** single-point energies on HF/6-31G** optimized structures. To achieve better agreement with the observed geometries of glycosidic linkages, the bond angles at the O-linkage atoms are added to the internal variable set and the corresponding bond bending energy term is parametrized using quantum mechanical data. The resulting force field is validated on glycan chains of 1-12 residues from a set of high-resolution X-ray glycoprotein structures based on heavy atom root-mean-square deviations of the lowest-energy glycan conformations generated by the biased probability Monte Carlo (BPMC) molecular mechanics simulations from the native structures. The appropriate BPMC distributions for monosaccharide-monosaccharide and protein-glycan linkages are derived from the

  11. All-atom polarizable force field for DNA based on the classical Drude oscillator model.

    PubMed

    Savelyev, Alexey; MacKerell, Alexander D

    2014-06-15

    Presented is a first generation atomistic force field (FF) for DNA in which electronic polarization is modeled based on the classical Drude oscillator formalism. The DNA model is based on parameters for small molecules representative of nucleic acids, including alkanes, ethers, dimethylphosphate, and the nucleic acid bases and empirical adjustment of key dihedral parameters associated with the phosphodiester backbone, glycosidic linkages, and sugar moiety of DNA. Our optimization strategy is based on achieving a compromise between satisfying the properties of the underlying model compounds in the gas phase targeting quantum mechanical (QM) data and reproducing a number of experimental properties of DNA duplexes in the condensed phase. The resulting Drude FF yields stable DNA duplexes on the 100-ns time scale and satisfactorily reproduce (1) the equilibrium between A and B forms of DNA and (2) transitions between the BI and BII substates of B form DNA. Consistency with the gas phase QM data for the model compounds is significantly better for the Drude model as compared to the CHARMM36 additive FF, which is suggested to be due to the improved response of the model to changes in the environment associated with the explicit inclusion of polarizability. Analysis of dipole moments associated with the nucleic acid bases shows the Drude model to have significantly larger values than those present in CHARMM36, with the dipoles of individual bases undergoing significant variations during the MD simulations. Additionally, the dipole moment of water was observed to be perturbed in the grooves of DNA.

  12. A robust all-atom model for LCAT generated by homology modeling[S

    PubMed Central

    Segrest, Jere P.; Jones, Martin K.; Catte, Andrea; Thirumuruganandham, Saravana P.

    2015-01-01

    LCAT is activated by apoA-I to form cholesteryl ester. We combined two structures, phospholipase A2 (PLA2) that hydrolyzes the ester bond at the sn-2 position of oxidized (short) acyl chains of phospholipid, and bacteriophage tubulin PhuZ, as C- and N-terminal templates, respectively, to create a novel homology model for human LCAT. The juxtaposition of multiple structural motifs matching experimental data is compelling evidence for the general correctness of many features of the model: i) The N-terminal 10 residues of the model, required for LCAT activity, extend the hydrophobic binding trough for the sn-2 chain 15–20 Å relative to PLA2. ii) The topography of the trough places the ester bond of the sn-2 chain less than 5 Å from the hydroxyl of the catalytic nucleophile, S181. iii) A β-hairpin resembling a lipase lid separates S181 from solvent. iv) S181 interacts with three functionally critical residues: E149, that regulates sn-2 chain specificity, and K128 and R147, whose mutations cause LCAT deficiency. Because the model provides a novel explanation for the complicated thermodynamic problem of the transfer of hydrophobic substrates from HDL to the catalytic triad of LCAT, it is an important step toward understanding the antiatherogenic role of HDL in reverse cholesterol transport. PMID:25589508

  13. Assembling a xylanase-lichenase chimera through all-atom molecular dynamics simulations.

    PubMed

    Cota, Junio; Oliveira, Leandro C; Damásio, André R L; Citadini, Ana P; Hoffmam, Zaira B; Alvarez, Thabata M; Codima, Carla A; Leite, Vitor B P; Pastore, Glaucia; de Oliveira-Neto, Mario; Murakami, Mario T; Ruller, Roberto; Squina, Fabio M

    2013-08-01

    Multifunctional enzyme engineering can improve enzyme cocktails for emerging biofuel technology. Molecular dynamics through structure-based models (SB) is an effective tool for assessing the tridimensional arrangement of chimeric enzymes as well as for inferring the functional practicability before experimental validation. This study describes the computational design of a bifunctional xylanase-lichenase chimera (XylLich) using the xynA and bglS genes from Bacillus subtilis. In silico analysis of the average solvent accessible surface area (SAS) and the root mean square fluctuation (RMSF) predicted a fully functional chimera, with minor fluctuations and variations along the polypeptide chains. Afterwards, the chimeric enzyme was built by fusing the xynA and bglS genes. XylLich was evaluated through small-angle X-ray scattering (SAXS) experiments, resulting in scattering curves with a very accurate fit to the theoretical protein model. The chimera preserved the biochemical characteristics of the parental enzymes, with the exception of a slight variation in the temperature of operation and the catalytic efficiency (kcat/Km). The absence of substantial shifts in the catalytic mode of operation was also verified. Furthermore, the production of chimeric enzymes could be more profitable than producing a single enzyme separately, based on comparing the recombinant protein production yield and the hydrolytic activity achieved for XylLich with that of the parental enzymes.

  14. Hierarchical atom type definitions and extensible all-atom force fields.

    PubMed

    Jin, Zhao; Yang, Chunwei; Cao, Fenglei; Li, Feng; Jing, Zhifeng; Chen, Long; Shen, Zhe; Xin, Liang; Tong, Sijia; Sun, Huai

    2016-03-15

    The extensibility of force field is a key to solve the missing parameter problem commonly found in force field applications. The extensibility of conventional force fields is traditionally managed in the parameterization procedure, which becomes impractical as the coverage of the force field increases above a threshold. A hierarchical atom-type definition (HAD) scheme is proposed to make extensible atom type definitions, which ensures that the force field developed based on the definitions are extensible. To demonstrate how HAD works and to prepare a foundation for future developments, two general force fields based on AMBER and DFF functional forms are parameterized for common organic molecules. The force field parameters are derived from the same set of quantum mechanical data and experimental liquid data using an automated parameterization tool, and validated by calculating molecular and liquid properties. The hydration free energies are calculated successfully by introducing a polarization scaling factor to the dispersion term between the solvent and solute molecules. © 2015 Wiley Periodicals, Inc.

  15. A robust all-atom model for LCAT generated by homology modeling.

    PubMed

    Segrest, Jere P; Jones, Martin K; Catte, Andrea; Thirumuruganandham, Saravana P

    2015-03-01

    LCAT is activated by apoA-I to form cholesteryl ester. We combined two structures, phospholipase A2 (PLA2) that hydrolyzes the ester bond at the sn-2 position of oxidized (short) acyl chains of phospholipid, and bacteriophage tubulin PhuZ, as C- and N-terminal templates, respectively, to create a novel homology model for human LCAT. The juxtaposition of multiple structural motifs matching experimental data is compelling evidence for the general correctness of many features of the model: i) The N-terminal 10 residues of the model, required for LCAT activity, extend the hydrophobic binding trough for the sn-2 chain 15-20 Å relative to PLA2. ii) The topography of the trough places the ester bond of the sn-2 chain less than 5 Å from the hydroxyl of the catalytic nucleophile, S181. iii) A β-hairpin resembling a lipase lid separates S181 from solvent. iv) S181 interacts with three functionally critical residues: E149, that regulates sn-2 chain specificity, and K128 and R147, whose mutations cause LCAT deficiency. Because the model provides a novel explanation for the complicated thermodynamic problem of the transfer of hydrophobic substrates from HDL to the catalytic triad of LCAT, it is an important step toward understanding the antiatherogenic role of HDL in reverse cholesterol transport.

  16. On the Helix Propensity in Generalized Born Solvent Descriptions of Modeling the Dark Proteome

    PubMed Central

    Olson, Mark A.

    2017-01-01

    Intrinsically disordered proteins that populate the so-called “Dark Proteome” offer challenging benchmarks of atomistic simulation methods to accurately model conformational transitions on a multidimensional energy landscape. This work explores the application of parallel tempering with implicit solvent models as a computational framework to capture the conformational ensemble of an intrinsically disordered peptide derived from the Ebola virus protein VP35. A recent X-ray crystallographic study reported a protein-peptide interface where the VP35 peptide underwent a folding transition from a disordered form to a helix-β-turn-helix topological fold upon molecular association with the Ebola protein NP. An assessment is provided of the accuracy of two generalized Born solvent models (GBMV2 and GBSW2) using the CHARMM force field and applied with temperature-based replica exchange dynamics to calculate the disorder propensity of the peptide and its probability density of states in a continuum solvent. A further comparison is presented of applying an explicit/implicit solvent hybrid replica exchange simulation of the peptide to determine the effect of modeling water interactions at the all-atom resolution. PMID:28197405

  17. All-atom simulation study of protein PTH(1-34) by using the Wang-Landau sampling method

    NASA Astrophysics Data System (ADS)

    Kim, Seung-Yeon; Kwak, Wooseop

    2014-12-01

    We perform simulations of the N-terminal 34-residue protein fragment PTH(1-34), consisting of 581 atoms, of the 84-residue human parathyroid hormone by using the all-atom ECEPP/3 force field and the Wang-Landau sampling method. Through a massive high-performance computation, the density of states and the partition function Z( T), as a continuous function of T, are obtained for PTH(1-34). From the continuous partition function Z( T), the partition function zeros of PTH(1-34) are evaluated for the first time. From both the specific heat and the partition function zeros, two characteristic transition temperatures are obtained for the all-atom protein PTH(1-34). The higher transition temperature T 1 and the lower transition temperature T 2 of PTH(1-34) can be interpreted as the collapse temperature T θ and the folding temperature T f , respectively.

  18. Refined OPLS all-atom force field parameters for n-pentadecane, methyl acetate, and dimethyl phosphate.

    PubMed

    Murzyn, Krzysztof; Bratek, Maciej; Pasenkiewicz-Gierula, Marta

    2013-12-27

    OPLS All-Atom (OPLS/AA) is a generic all-atom force field which was fine-tuned to accurately reproduce condensed phase properties of organic liquids. Its application in modeling of lipid membranes is, however, limited mainly due to the inability to correctly describe phase behavior and organization of the hydrophobic core of the model lipid bilayers. Here we report new OPLS/AA parameters for n-pentadecane, methyl acetate, and dimethyl phosphate anion. For the new force field parameters, we show very good agreement between calculated and numerous reference data, including liquid density, enthalpy of vaporization, free energy of hydration, and selected transport properties. The new OPLS/AA parameters have been used in successful submicrosecond MD simulations of bilayers made of bacterial glycolipids whose results will be published elsewhere shortly.

  19. Local order parameters for use in driving homogeneous ice nucleation with all-atom models of water.

    PubMed

    Reinhardt, Aleks; Doye, Jonathan P K; Noya, Eva G; Vega, Carlos

    2012-11-21

    We present a local order parameter based on the standard Steinhardt-Ten Wolde approach that is capable both of tracking and of driving homogeneous ice nucleation in simulations of all-atom models of water. We demonstrate that it is capable of forcing the growth of ice nuclei in supercooled liquid water simulated using the TIP4P/2005 model using over-biassed umbrella sampling Monte Carlo simulations. However, even with such an order parameter, the dynamics of ice growth in deeply supercooled liquid water in all-atom models of water are shown to be very slow, and so the computation of free energy landscapes and nucleation rates remains extremely challenging.

  20. An Evolutionary Strategy for All-Atom Folding of the 60-Amino-Acid Bacterial Ribosomal Protein L20

    PubMed Central

    Schug, A.; Wenzel, W.

    2006-01-01

    We have investigated an evolutionary algorithm for de novo all-atom folding of the bacterial ribosomal protein L20. We report results of two simulations that converge to near-native conformations of this 60-amino-acid, four-helix protein. We observe a steady increase of “native content” in both simulated ensembles and a large number of near-native conformations in their final populations. We argue that these structures represent a significant fraction of the low-energy metastable conformations, which characterize the folding funnel of this protein. These data validate our all-atom free-energy force field PFF01 for tertiary structure prediction of a previously inaccessible structural family of proteins. We also compare folding simulations of the evolutionary algorithm with the basin-hopping technique for the Trp-cage protein. We find that the evolutionary algorithm generates a dynamic memory in the simulated population, which leads to faster overall convergence. PMID:16565067

  1. Bridging between NMA and Elastic Network Models: Preserving All-Atom Accuracy in Coarse-Grained Models.

    PubMed

    Na, Hyuntae; Jernigan, Robert L; Song, Guang

    2015-10-01

    Dynamics can provide deep insights into the functional mechanisms of proteins and protein complexes. For large protein complexes such as GroEL/GroES with more than 8,000 residues, obtaining a fine-grained all-atom description of its normal mode motions can be computationally prohibitive and is often unnecessary. For this reason, coarse-grained models have been used successfully. However, most existing coarse-grained models use extremely simple potentials to represent the interactions within the coarse-grained structures and as a result, the dynamics obtained for the coarse-grained structures may not always be fully realistic. There is a gap between the quality of the dynamics of the coarse-grained structures given by all-atom models and that by coarse-grained models. In this work, we resolve an important question in protein dynamics computations--how can we efficiently construct coarse-grained models whose description of the dynamics of the coarse-grained structures remains as accurate as that given by all-atom models? Our method takes advantage of the sparseness of the Hessian matrix and achieves a high efficiency with a novel iterative matrix projection approach. The result is highly significant since it can provide descriptions of normal mode motions at an all-atom level of accuracy even for the largest biomolecular complexes. The application of our method to GroEL/GroES offers new insights into the mechanism of this biologically important chaperonin, such as that the conformational transitions of this protein complex in its functional cycle are even more strongly connected to the first few lowest frequency modes than with other coarse-grained models.

  2. Capturing the multiscale dynamics of membrane protein complexes with all-atom, mixed-resolution, and coarse-grained models.

    PubMed

    Liao, Chenyi; Zhao, Xiaochuan; Liu, Jiyuan; Schneebeli, Severin T; Shelley, John C; Li, Jianing

    2017-03-20

    The structures and dynamics of protein complexes are often challenging to model in heterogeneous environments such as biological membranes. Herein, we meet this fundamental challenge at attainable cost with all-atom, mixed-resolution, and coarse-grained models of vital membrane proteins. We systematically simulated five complex models formed by two distinct G protein-coupled receptors (GPCRs) in the lipid-bilayer membrane on the ns-to-μs timescales. These models, which suggest the swinging motion of an intracellular loop, for the first time, provide the molecular details for the regulatory role of such a loop. For the models at different resolutions, we observed consistent structural stability but various levels of speed-ups in protein dynamics. The mixed-resolution and coarse-grained models show two and four times faster protein diffusion than the all-atom models, in addition to a 4- and 400-fold speed-up in the simulation performance. Furthermore, by elucidating the strengths and challenges of combining all-atom models with reduced resolution models, this study can serve as a guide to simulating other complex systems in heterogeneous environments efficiently.

  3. The tilt-dependent potential of mean force of a pair of DNA oligomers from all-atom molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Cortini, Ruggero; Cheng, Xiaolin; Smith, Jeremy C.

    2017-03-01

    Electrostatic interactions between DNA molecules have been extensively studied experimentally and theoretically, but several aspects (e.g. its role in determining the pitch of the cholesteric DNA phase) still remain unclear. Here, we performed large-scale all-atom molecular dynamics simulations in explicit water and 150 mM sodium chloride, to reconstruct the potential of mean force (PMF) of two DNA oligomers 24 base pairs long as a function of their interaxial angle and intermolecular distance. We find that the potential of mean force is dominated by total DNA charge, and not by the helical geometry of its charged groups. The theory of homogeneously charged cylinders fits well all our simulation data, and the fit yields the optimal value of the total compensated charge on DNA to  ≈65% of its total fixed charge (arising from the phosphorous atoms), close to the value expected from Manning’s theory of ion condensation. The PMF calculated from our simulations does not show a significant dependence on the handedness of the angle between the two DNA molecules, or its size is on the order of 1{{k}\\text{B}}T . Thermal noise for molecules of the studied length seems to mask the effect of detailed helical charge patterns of DNA. The fact that in monovalent salt the effective interaction between two DNA molecules is independent on the handedness of the tilt may suggest that alternative mechanisms are required to understand the cholesteric phase of DNA.

  4. Molecular structure of poly(methyl methacrylate) surface II: Effect of stereoregularity examined through all-atom molecular dynamics.

    PubMed

    Jha, Kshitij C; Zhu, He; Dhinojwala, Ali; Tsige, Mesfin

    2014-11-04

    Utilizing all-atom molecular dynamics (MD), we have analyzed the effect of tacticity and temperature on the surface structure of poly(methyl methacrylate) (PMMA) at the polymer-vacuum interface. We quantify these effects primarily through orientation, measured as the tilt with respect to the surface normal, and the surface number densities of the α-methyl, ester-methyl, carbonyl, and backbone methylene groups. Molecular structure on the surface is a complex interplay between orientation and number densities and is challenging to capture through sum frequency generation (SFG) spectroscopy alone. Independent quantification of the number density and orientation of chemical groups through all-atom MD presents a comprehensive model of stereoregular PMMA on the surface. SFG analysis presented in part I of this joint publication measures the orientation of molecules that are in agreement with MD results. We observe the ester-methyl groups as preferentially oriented, irrespective of tacticity, followed by the α-methyl and carbonyl groups. SFG spectroscopy also points to ester-methyl being dominant on the surface. The backbone methylene groups show a very broad angular distribution, centered along the surface plane. The surface number density ratios of ester-methyl to α-methyl groups show syndiotactic PMMA having the lowest value. Isotactic PMMA has the highest ratios of ester- to α-methyl. These subtle trends in the relative angular orientation and number densities that influence the variation of surface structure with tacticity are highlighted in this article. A more planar conformation of the syndiotactic PMMA along the surface (x-y plane) can be visualized through the trajectories from all-atom MD. Results from conformation tensor calculations for chains with any of their segments contributing to the surface validate the visual observation.

  5. Calculating the binding free energies of charged species based on explicit-solvent simulations employing lattice-sum methods: An accurate correction scheme for electrostatic finite-size effects

    SciTech Connect

    Rocklin, Gabriel J.; Mobley, David L.; Dill, Ken A.; Hünenberger, Philippe H.

    2013-11-14

    -periodic PB calculations for a given system, its dependence on the box size being analytical. The latter scheme also provides insight into the physical origin of the finite-size effects. These two schemes also encompass a correction for discrete solvent effects that persists even in the limit of infinite box sizes. Application of either scheme essentially eliminates the size dependence of the corrected charging free energies (maximal deviation of 1.5 kJ mol{sup −1}). Because it is simple to apply, the analytical correction scheme offers a general solution to the problem of finite-size effects in free-energy calculations involving charged solutes, as encountered in calculations concerning, e.g., protein-ligand binding, biomolecular association, residue mutation, pK{sub a} and redox potential estimation, substrate transformation, solvation, and solvent-solvent partitioning.

  6. Calculating the binding free energies of charged species based on explicit-solvent simulations employing lattice-sum methods: An accurate correction scheme for electrostatic finite-size effects

    PubMed Central

    Rocklin, Gabriel J.; Mobley, David L.; Dill, Ken A.; Hünenberger, Philippe H.

    2013-01-01

    calculations for a given system, its dependence on the box size being analytical. The latter scheme also provides insight into the physical origin of the finite-size effects. These two schemes also encompass a correction for discrete solvent effects that persists even in the limit of infinite box sizes. Application of either scheme essentially eliminates the size dependence of the corrected charging free energies (maximal deviation of 1.5 kJ mol−1). Because it is simple to apply, the analytical correction scheme offers a general solution to the problem of finite-size effects in free-energy calculations involving charged solutes, as encountered in calculations concerning, e.g., protein-ligand binding, biomolecular association, residue mutation, pKa and redox potential estimation, substrate transformation, solvation, and solvent-solvent partitioning. PMID:24320250

  7. All-Atom Molecular-Level Analysis of the Ballistic-Impact-Induced Densification and Devitrification of Fused Silica

    NASA Astrophysics Data System (ADS)

    Grujicic, M.; Snipes, J. S.; Ramaswami, S.; Yavari, R.; Barsoum, R. S.

    2015-08-01

    All-atom molecular-level computations are carried out to infer the dynamic response and material microstructure/topology changes of fused silica subjected to ballistic impact by a hard projectile. The analysis was focused on the investigation of specific aspects of the dynamic response and of the microstructural changes such as the deformation of highly sheared and densified regions and the conversion of amorphous fused silica to SiO2 crystalline allotropic modifications (in particular, α-quartz and stishovite). The microstructural changes in question were determined by carrying out a post-processing atom-coordination procedure. This procedure suggested the formation of stishovite (and perhaps α-quartz) within fused silica during ballistic impact. To rationalize the findings obtained, the all-atom molecular-level computational analysis is complemented by a series of quantum-mechanics density functional theory (DFT) computations. The latter computations enable determination of the relative potential energies of the fused silica, α-quartz, and stishovite under ambient pressure (i.e., under their natural densities) as well as under imposed (as high as 50 GPa) pressures (i.e., under higher densities) and shear strains. In addition, the transition states associated with various fused-silica devitrification processes were identified. The results obtained are found to be in good agreement with their respective experimental counterparts.

  8. Replica exchange molecular dynamics simulations of coarse-grained proteins in implicit solvent.

    PubMed

    Chebaro, Yassmine; Dong, Xiao; Laghaei, Rozita; Derreumaux, Philippe; Mousseau, Normand

    2009-01-08

    Current approaches aimed at determining the free energy surface of all-atom medium-size proteins in explicit solvent are slow and are not sufficient to converge to equilibrium properties. To ensure a proper sampling of the configurational space, it is preferable to use reduced representations such as implicit solvent and/or coarse-grained protein models, which are much lighter computationally. Each model must be verified, however, to ensure that it can recover experimental structures and thermodynamics. Here we test the coarse-grained implicit solvent OPEP model with replica exchange molecular dynamics (REMD) on six peptides ranging in length from 10 to 28 residues: two alanine-based peptides, the second beta-hairpin from protein G, the Trp-cage and zinc-finger motif, and a dimer of a coiled coil peptide. We show that REMD-OPEP recovers the proper thermodynamics of the systems studied, with accurate structural description of the beta-hairpin and Trp-cage peptides (within 1-2 A from experiments). The light computational burden of REMD-OPEP, which enables us to generate many hundred nanoseconds at each temperature and fully assess convergence to equilibrium ensemble, opens the door to the determination of the free energy surface of larger proteins and assemblies.

  9. Cholesterol Flip-Flop Dynamics in a Phospholipid Bilayer: A 10 Microsecond All-Atom Molecular Dynamics Simulation

    NASA Astrophysics Data System (ADS)

    Choubey, Amit; Nomura, Ken-Ichi; Kalia, Rajiv; Nakano, Aiichiro; Vashishta, Priya

    2012-02-01

    Cholesterol (CHOL) molecules play a key role in modulating the rigidity of cell membranes, and controlling intracellular transport and signal transduction. Using all-atom molecular dynamics and the parallel replica approach, we study the effect of CHOL molecules on mechanical stresses across a dipalmitoylphosphatidycholine (DPPC)-CHOL bilayer, and the mechanism by which CHOL molecules migrate from one bilayer leaflet to the other (flip-flop events). On average, we observe a CHOL flip-flop event in half-a-microsecond. Once a CHOL flip-flop event is triggered, the inter-leaflet migration occurs in about 62 nanoseconds. The energy barrier associated with flip-flop events is found to be 73 kJ/mol. Results for membrane rigidity as a function of CHOL concentration will also be presented.

  10. Mechanism of Nucleation and Growth of Aβ40 Fibrils from All-Atom and Coarse-Grained Simulations.

    PubMed

    Sasmal, Sukanya; Schwierz, Nadine; Head-Gordon, Teresa

    2016-12-01

    In this work, we characterize the nucleation and elongation mechanisms of the "diseased" polymorph of the amyloid-β 40 (Aβ40) fibril using an off-lattice coarse-grained (CG) protein model. After determining the nucleation size and subsequent stable protofibrillar structure from the CG model, validated with all-atom simulations, we consider the "lock and dock" and "activated monomer" fibril elongation mechanisms for the protofibril by statistical additions of a monomer drawn from four different ensembles of the free Aβ40 peptide to grow the fibril. Our CG model shows that the dominant mechanism for fibril elongation is the lock and dock mechanism across all monomer ensembles, even when the monomer is in the activated form. Although our CG model finds no thermodynamic difference between the two fibril elongation mechanisms, the activated monomer is found to be kinetically faster by a factor of 2 for the "locking" step compared with all other structured or unstructured monomer ensembles.

  11. Estimation of Liposome Penetration Barriers of Drug Molecules with All-Atom and Coarse-Grained Models.

    PubMed

    Genheden, Samuel; Eriksson, Leif A

    2016-09-13

    Liposomes are common carriers of drug molecules, providing enhanced delivery and accumulation of hydrophilic agents or larger biomolecules. Molecular simulations can be used to estimate key features of the drug molecules upon interaction with the liposomes, such as penetration barriers and localization. Herein, we investigate several aspects of the computational estimation of penetration barriers, viz. the potential of mean force (PMFs) along a vector spanning the membrane. First, we provide an evaluation of the all-atom (AA) and coarse-grained (CG) parametrization of 5-aminolevulinic acid (5-ALA) and two of its alkyl esters by computing n-octanol/water partition coefficients. We find that the CG parametrization of the esters performs significantly better than the CG model of 5-ALA, highlighting the difficulty to coarse-grain small, polar molecules. However, the expected trend in partition coefficients is reproduced also with the CG models. Second, we compare PMFs in a small membrane slab described with either the AA or CG models. Here, we are able to reproduce the all-atom PMF of 5-ALA with CG. However, for the alkyl esters it is unfortunately not possible to correctly reproduce both the depth and the penetration barrier of the PMF seen in the AA simulations with any of the tested CG models. We argue that it is more important to choose a CG parametrization that reproduces the depth of the PMF. Third, we compare, using the CG model, PMFs in the membrane slab with PMFs in a large, realistic liposome. We find similar depths but slightly different penetration barriers most likely due to differences in the lipid density along the membrane axis. Finally, we compute PMFs in liposomes with three different lipid compositions. Unfortunately, differences in the PMFs could not be quantified, and it remains to be investigated to what extent liposome simulations can fully reproduce experimental findings.

  12. Analysis of Ligand-Receptor Association and Intermediate Transfer Rates in Multienzyme Nanostructures with All-Atom Brownian Dynamics Simulations.

    PubMed

    Roberts, Christopher C; Chang, Chia-En A

    2016-08-25

    We present the second-generation GeomBD Brownian dynamics software for determining interenzyme intermediate transfer rates and substrate association rates in biomolecular complexes. Substrate and intermediate association rates for a series of enzymes or biomolecules can be compared between the freely diffusing disorganized configuration and various colocalized or complexed arrangements for kinetic investigation of enhanced intermediate transfer. In addition, enzyme engineering techniques, such as synthetic protein conjugation, can be computationally modeled and analyzed to better understand changes in substrate association relative to native enzymes. Tools are provided to determine nonspecific ligand-receptor association residence times, and to visualize common sites of nonspecific association of substrates on receptor surfaces. To demonstrate features of the software, interenzyme intermediate substrate transfer rate constants are calculated and compared for all-atom models of DNA origami scaffold-bound bienzyme systems of glucose oxidase and horseradish peroxidase. Also, a DNA conjugated horseradish peroxidase enzyme was analyzed for its propensity to increase substrate association rates and substrate local residence times relative to the unmodified enzyme. We also demonstrate the rapid determination and visualization of common sites of nonspecific ligand-receptor association by using HIV-1 protease and an inhibitor, XK263. GeomBD2 accelerates simulations by precomputing van der Waals potential energy grids and electrostatic potential grid maps, and has a flexible and extensible support for all-atom and coarse-grained force fields. Simulation software is written in C++ and utilizes modern parallelization techniques for potential grid preparation and Brownian dynamics simulation processes. Analysis scripts, written in the Python scripting language, are provided for quantitative simulation analysis. GeomBD2 is applicable to the fields of biophysics, bioengineering

  13. Insights into the Tunnel Mechanism of Cholesteryl Ester Transfer Protein through All-atom Molecular Dynamics Simulations*

    PubMed Central

    Lei, Dongsheng; Rames, Matthew; Zhang, Xing; Zhang, Lei; Zhang, Shengli; Ren, Gang

    2016-01-01

    Cholesteryl ester transfer protein (CETP) mediates cholesteryl ester (CE) transfer from the atheroprotective high density lipoprotein (HDL) cholesterol to the atherogenic low density lipoprotein cholesterol. In the past decade, this property has driven the development of CETP inhibitors, which have been evaluated in large scale clinical trials for treating cardiovascular diseases. Despite the pharmacological interest, little is known about the fundamental mechanism of CETP in CE transfer. Recent electron microscopy (EM) experiments have suggested a tunnel mechanism, and molecular dynamics simulations have shown that the flexible N-terminal distal end of CETP penetrates into the HDL surface and takes up a CE molecule through an open pore. However, it is not known whether a CE molecule can completely transfer through an entire CETP molecule. Here, we used all-atom molecular dynamics simulations to evaluate this possibility. The results showed that a hydrophobic tunnel inside CETP is sufficient to allow a CE molecule to completely transfer through the entire CETP within a predicted transfer time and at a rate comparable with those obtained through physiological measurements. Analyses of the detailed interactions revealed several residues that might be critical for CETP function, which may provide important clues for the effective development of CETP inhibitors and treatment of cardiovascular diseases. PMID:27143480

  14. Effects of system net charge and electrostatic truncation on all-atom constant pH molecular dynamics.

    PubMed

    Chen, Wei; Shen, Jana K

    2014-10-15

    Constant pH molecular dynamics offers a means to rigorously study the effects of solution pH on dynamical processes. Here, we address two critical questions arising from the most recent developments of the all-atom continuous constant pH molecular dynamics (CpHMD) method: (1) What is the effect of spatial electrostatic truncation on the sampling of protonation states? (2) Is the enforcement of electrical neutrality necessary for constant pH simulations? We first examined how the generalized reaction field and force-shifting schemes modify the electrostatic forces on the titration coordinates. Free energy simulations of model compounds were then carried out to delineate the errors in the deprotonation free energy and salt-bridge stability due to electrostatic truncation and system net charge. Finally, CpHMD titration of a mini-protein HP36 was used to understand the manifestation of the two types of errors in the calculated pK(a) values. The major finding is that enforcing charge neutrality under all pH conditions and at all time via cotitrating ions significantly improves the accuracy of protonation-state sampling. We suggest that such finding is also relevant for simulations with particle mesh Ewald, considering the known artifacts due to charge-compensating background plasma.

  15. Multi-step formation of a hemifusion diaphragm for vesicle fusion revealed by all-atom molecular dynamics simulations.

    PubMed

    Tsai, Hui-Hsu Gavin; Chang, Che-Ming; Lee, Jian-Bin

    2014-06-01

    Membrane fusion is essential for intracellular trafficking and virus infection, but the molecular mechanisms underlying the fusion process remain poorly understood. In this study, we employed all-atom molecular dynamics simulations to investigate the membrane fusion mechanism using vesicle models which were pre-bound by inter-vesicle Ca(2+)-lipid clusters to approximate Ca(2+)-catalyzed fusion. Our results show that the formation of the hemifusion diaphragm for vesicle fusion is a multi-step event. This result contrasts with the assumptions made in most continuum models. The neighboring hemifused states are separated by an energy barrier on the energy landscape. The hemifusion diaphragm is much thinner than the planar lipid bilayers. The thinning of the hemifusion diaphragm during its formation results in the opening of a fusion pore for vesicle fusion. This work provides new insights into the formation of the hemifusion diaphragm and thus increases understanding of the molecular mechanism of membrane fusion. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.

  16. Structure and function of photosystem I–[FeFe] hydrogenase protein fusions: An all-atom molecular dynamics study

    DOE PAGES

    Harris, Bradley J.; Cheng, Xiaolin; Frymier, Paul

    2015-12-15

    All-atom molecular dynamics (MD) simulation was used to study the solution dynamics and protein protein interactions of protein fusions of photosystem I (PSI) from Thermosynechococcus elongatus and an [FeFe]-hydrogenase (FeFe H2ase) from Clostridium pasteurianum, a unique complex capable of photocatalytic hydrogen production. This study involved fusions of these two proteins via dithiol linkers of different length including decanedithiol, octanedithiol, and hexanedithiol, for which experimental data had previously been obtained. Evaluation of root-mean-squared deviations (RMSDs) relative to the respective crystal structures of PSI and the FeFe H2ase shows that these fusion complexes approach stable equilibrium conformations during the MD simulations. Investigatingmore » protein mobility via root-mean-squared fluctuations (RMSFs) reveals that tethering via the shortest hexanedithiol linker results in increased atomic fluctuations of both PSI and the hydrogenase in these fusion complexes. Furthermore, evaluation of the inter- and intraprotein electron transfer distances in these fusion complexes indicates that the structural changes in the FeFe H2ase arising from ligation to PSI via the shortest hexanedithiol linker may hinder electron transport in the hydrogenase, thus providing a molecular level explanation for the observation that the medium-length octanedithiol linker gives the highest hydrogen production rate.« less

  17. Structure and function of photosystem I–[FeFe] hydrogenase protein fusions: An all-atom molecular dynamics study

    SciTech Connect

    Harris, Bradley J.; Cheng, Xiaolin; Frymier, Paul

    2015-12-15

    All-atom molecular dynamics (MD) simulation was used to study the solution dynamics and protein protein interactions of protein fusions of photosystem I (PSI) from Thermosynechococcus elongatus and an [FeFe]-hydrogenase (FeFe H2ase) from Clostridium pasteurianum, a unique complex capable of photocatalytic hydrogen production. This study involved fusions of these two proteins via dithiol linkers of different length including decanedithiol, octanedithiol, and hexanedithiol, for which experimental data had previously been obtained. Evaluation of root-mean-squared deviations (RMSDs) relative to the respective crystal structures of PSI and the FeFe H2ase shows that these fusion complexes approach stable equilibrium conformations during the MD simulations. Investigating protein mobility via root-mean-squared fluctuations (RMSFs) reveals that tethering via the shortest hexanedithiol linker results in increased atomic fluctuations of both PSI and the hydrogenase in these fusion complexes. Furthermore, evaluation of the inter- and intraprotein electron transfer distances in these fusion complexes indicates that the structural changes in the FeFe H2ase arising from ligation to PSI via the shortest hexanedithiol linker may hinder electron transport in the hydrogenase, thus providing a molecular level explanation for the observation that the medium-length octanedithiol linker gives the highest hydrogen production rate.

  18. Peptide Aggregation and Pore Formation in a Lipid Bilayer: A Combined Coarse-Grained and All Atom Molecular Dynamics Study

    PubMed Central

    Thøgersen, Lea; Schiøtt, Birgit; Vosegaard, Thomas; Nielsen, Niels Chr.; Tajkhorshid, Emad

    2008-01-01

    We present a simulation study where different resolutions, namely coarse-grained (CG) and all-atom (AA) molecular dynamics simulations, are used sequentially to combine the long timescale reachable by CG simulations with the high resolution of AA simulations, to describe the complete processes of peptide aggregation and pore formation by alamethicin peptides in a hydrated lipid bilayer. In the 1-μs CG simulations the peptides spontaneously aggregate in the lipid bilayer and exhibit occasional transitions between the membrane-spanning and the surface-bound configurations. One of the CG systems at t = 1 μs is reverted to an AA representation and subjected to AA simulation for 50 ns, during which water molecules penetrate the lipid bilayer through interactions with the peptide aggregates, and the membrane starts leaking water. During the AA simulation significant deviations from the α-helical structure of the peptides are observed, however, the size and arrangement of the clusters are not affected within the studied time frame. Solid-state NMR experiments designed to match closely the setup used in the molecular dynamics simulations provide strong support for our finding that alamethicin peptides adopt a diverse set of configurations in a lipid bilayer, which is in sharp contrast to the prevailing view of alamethicin oligomers formed by perfectly aligned helical alamethicin peptides in a lipid bilayer. PMID:18676652

  19. Nonequilibrium all-atom molecular dynamics simulation of the bubble cavitation and application to dissociate amyloid fibrils

    NASA Astrophysics Data System (ADS)

    Hoang Viet, Man; Derreumaux, Philippe; Nguyen, Phuong H.

    2016-11-01

    The cavitation of gas bubbles in liquids has been applied to different disciplines in life and natural sciences, and in technologies. To obtain an appropriate theoretical description of effects induced by the bubble cavitation, we develop an all-atom nonequilibrium molecular-dynamics simulation method to simulate bubbles undergoing harmonic oscillation in size. This allows us to understand the mechanism of the bubble cavitation-induced liquid shear stress on surrounding objects. The method is then employed to simulate an Aβ fibril model in the presence of bubbles, and the results show that the bubble expansion and contraction exert water pressure on the fibril. This yields to the deceleration and acceleration of the fibril kinetic energy, facilitating the conformational transition between local free energy minima, and leading to the dissociation of the fibril. Our work, which is a proof-of-concept, may open a new, efficient way to dissociate amyloid fibrils using the bubble cavitation technique, and new venues to investigate the complex phenomena associated with amyloidogenesis.

  20. Two-dimensional NMR and All-atom Molecular Dynamics of Cytochrome P450 CYP119 Reveal Hidden Conformational Substates*

    PubMed Central

    Lampe, Jed N.; Brandman, Relly; Sivaramakrishnan, Santhosh; de Montellano, Paul R. Ortiz

    2010-01-01

    Cytochrome P450 enzymes are versatile catalysts involved in a wide variety of biological processes from hormonal regulation and antibiotic synthesis to drug metabolism. A hallmark of their versatility is their promiscuous nature, allowing them to recognize a wide variety of chemically diverse substrates. However, the molecular details of this promiscuity have remained elusive. Here, we have utilized two-dimensional heteronuclear single quantum coherence NMR spectroscopy to examine a series of mutants site-specific labeled with the unnatural amino acid, [13C]p-methoxyphenylalanine, in conjunction with all-atom molecular dynamics simulations to examine substrate and inhibitor binding to CYP119, a P450 from Sulfolobus acidocaldarius. The results suggest that tight binding hydrophobic ligands tend to lock the enzyme into a single conformational substate, whereas weak binding low affinity ligands bind loosely in the active site, resulting in a distribution of localized conformers. Furthermore, the molecular dynamics simulations suggest that the ligand-free enzyme samples ligand-bound conformations of the enzyme and, therefore, that ligand binding may proceed largely through a process of conformational selection rather than induced fit. PMID:20097757

  1. A Hybrid All-Atom Structure-Based Model for Protein Folding and Large Scale Conformational Transitions.

    PubMed

    Sutto, Ludovico; Mereu, Ilaria; Gervasio, Francesco Luigi

    2011-12-13

    Structure-based models are successful at conjugating the essence of the energy landscape theory of protein folding with an easy and efficient implementation. Recently, their realm expanded beyond a single protein structure, and structure-based potentials have been used profitably to widely study complex conformational transitions. Still, when dealing with structural rearrangements between two, or more, well-defined structures, an unbiased and transferable description of the local backbone and side chain interactions could be advantageous. Here, we propose an all-atom model that merges a classical force field description of these local interactions with a structure-based long-range potential that takes into account the different conformations. We first validate the model simulating and characterizing the folding reaction and the transition state of two well-known proteins: the villin headpiece and the SH3 domain. Then, we characterize the activation mechanism of the catalytic domain of c-Src kinase. Such a process involves the conformational rearrangement of a large loop and the swing of an α helix. The appearance of a stable intermediate state in the free energy landscape between the two conformational end points suggests the mechanism of the loop opening. The low computational cost of the model together with the satisfactory accuracy of the results make it a promising approach to studying conformational transitions in large protein systems.

  2. Template-free protein structure prediction and quality assessment with an all-atom free-energy model.

    PubMed

    Gopal, Srinivasa Murthy; Klenin, Konstantin; Wenzel, Wolfgang

    2009-11-01

    Biophysical forcefields have contributed less than originally anticipated to recent progress in protein structure prediction. Here, we have investigated the selectivity of a recently developed all-atom free-energy forcefield for protein structure prediction and quality assessment (QA). Using a heuristic method, but excluding homology, we generated decoy-sets for all targets of the CASP7 protein structure prediction assessment with <150 amino acids. The decoys in each set were then ranked by energy in short relaxation simulations and the best low-energy cluster was submitted as a prediction. For four of nine template-free targets, this approach generated high-ranking predictions within the top 10 models submitted in CASP7 for the respective targets. For these targets, our de-novo predictions had an average GDT_S score of 42.81, significantly above the average of all groups. The refinement protocol has difficulty for oligomeric targets and when no near-native decoys are generated in the decoy library. For targets with high-quality decoy sets the refinement approach was highly selective. Motivated by this observation, we rescored all server submissions up to 200 amino acids using a similar refinement protocol, but using no clustering, in a QA exercise. We found an excellent correlation between the best server models and those with the lowest energy in the forcefield. The free-energy refinement protocol may thus be an efficient tool for relative QA and protein structure prediction.

  3. Dynamic performance of duolayers at the air/water interface. 2. Mechanistic insights from all-atom simulations.

    PubMed

    Christofferson, Andrew J; Yiapanis, George; Leung, Andy H M; Prime, Emma L; Tran, Diana N H; Qiao, Greg G; Solomon, David H; Yarovsky, Irene

    2014-09-18

    The novel duolayer system, comprising a monolayer of ethylene glycol monooctadecyl ether (C18E1) and the water-soluble polymer poly(vinylpyrrolidone) (PVP), has been shown to resist forces such as wind stress to a greater degree than the C18E1 monolayer alone. This paper reports all-atom molecular dynamics simulations comparing the monolayer (C18E1 alone) and duolayer systems under an applied force parallel to the air/water interface. The simulations show that, due to the presence of PVP at the interface, the duolayer film exhibits an increase in chain tilt, ordering, and density, as well as a lower lateral velocity compared to the monolayer. These results provide a molecular rationale for the improved performance of the duolayer system under wind conditions, as well as an atomic-level explanation for the observed efficacy of the duolayer system as an evaporation suppressant, which may serve as a useful guide for future development for thin films where resistance to external perturbation is desirable.

  4. Multiscale molecular dynamics simulations of sodium dodecyl sulfate micelles: from coarse-grained to all-atom resolution.

    PubMed

    Roussel, Guillaume; Michaux, Catherine; Perpète, Eric A

    2014-10-01

    Sodium dodecyl sulfate (SDS) is a well-known anionic detergent widely used in both experimental and theoretical investigations. Many molecular dynamics (MD) simulation have been performed on the SDS molecule at coarse-grained (CG), united-atom (UA), and all-atom (AA) resolutions. However, these simulations are usually based on general parameters determined from large sets of molecules, and as a result, peculiar molecular specificities are often poorly represented. In addition, the parameters (ideal bond lengths, angles, dihedrals and charge distribution) differ according to the resolution, highlighting a lack of coherence. We therefore propose a new set of parameters for CG, UA, and AA resolutions based on a high quantum mechanics (QM) level optimization of the detergent structure and the charge distribution. For the first time, QM-optimized parameters were directly applied to build the AA, UA, and CG model of the SDS molecule, leading to a more coherent description. As a test case, MD simulations were then performed on SDS preformed micelles as previous experimental and theoretical investigations allow direct comparison with our new sets of parameters. While all three models yield similar macromolecular properties (size, shape, and accessible surface) perfectly matching previous results, the attribution of more coherent parameters to SDS enables the description of the specific interactions inside and outside the micelle. These more consistent parameters can now be used to accurately describe new multi-scale systems involving the SDS molecule.

  5. Exploring Hamiltonian dielectric solvent molecular dynamics

    NASA Astrophysics Data System (ADS)

    Bauer, Sebastian; Tavan, Paul; Mathias, Gerald

    2014-09-01

    Hamiltonian dielectric solvent (HADES) is a recent method [7,25], which enables Hamiltonian molecular dynamics (MD) simulations of peptides and proteins in dielectric continua. Sample simulations of an α-helical decapeptide with and without explicit solvent demonstrate the high efficiency of HADES-MD. Addressing the folding of this peptide by replica exchange MD we study the properties of HADES by comparing melting curves, secondary structure motifs and salt bridges with explicit solvent results. Despite the unoptimized ad hoc parametrization of HADES, calculated reaction field energies correlate well with numerical grid solutions of the dielectric Poisson equation.

  6. Solvent substitution

    SciTech Connect

    Not Available

    1990-01-01

    The DOE Environmental Restoration and Waste Management Office of Technology Development and the Air Force Engineering and Services Center convened the First Annual International Workshop on Solvent Substitution on December 4--7, 1990. The primary objectives of this joint effort were to share information and ideas among attendees in order to enhance the development and implementation of required new technologies for the elimination of pollutants associated with industrial use of hazardous and toxic solvents; and to aid in accelerating collaborative efforts and technology transfer between government and industry for solvent substitution. There were workshop sessions focusing on Alternative Technologies, Alternative Solvents, Recovery/Recycling, Low VOC Materials and Treatment for Environmentally Safe Disposal. The 35 invited papers presented covered a wide range of solvent substitution activities including: hardware and weapons production and maintenance, paint stripping, coating applications, printed circuit boards, metal cleaning, metal finishing, manufacturing, compliance monitoring and process control monitoring. This publication includes the majority of these presentations. In addition, in order to further facilitate information exchange and technology transfer, the US Air Force and DOE solicited additional papers under a general Call for Papers.'' These papers, which underwent review and final selection by a peer review committee, are also included in this combined Proceedings/Compendium. For those involved in handling, using or managing hazardous and toxic solvents, this document should prove to be a valuable resource, providing the most up-to-date information on current technologies and practices in solvent substitution. Individual papers are abstracted separated.

  7. Folding processes of the B domain of protein A to the native state observed in all-atom ab initio folding simulations

    NASA Astrophysics Data System (ADS)

    Lei, Hongxing; Wu, Chun; Wang, Zhi-Xiang; Zhou, Yaoqi; Duan, Yong

    2008-06-01

    Reaching the native states of small proteins, a necessary step towards a comprehensive understanding of the folding mechanisms, has remained a tremendous challenge to ab initio protein folding simulations despite the extensive effort. In this work, the folding process of the B domain of protein A (BdpA) has been simulated by both conventional and replica exchange molecular dynamics using AMBER FF03 all-atom force field. Started from an extended chain, a total of 40 conventional (each to 1.0 μs) and two sets of replica exchange (each to 200.0 ns per replica) molecular dynamics simulations were performed with different generalized-Born solvation models and temperature control schemes. The improvements in both the force field and solvent model allowed successful simulations of the folding process to the native state as demonstrated by the 0.80 A˚ Cα root mean square deviation (RMSD) of the best folded structure. The most populated conformation was the native folded structure with a high population. This was a significant improvement over the 2.8 A˚ Cα RMSD of the best nativelike structures from previous ab initio folding studies on BdpA. To the best of our knowledge, our results demonstrate, for the first time, that ab initio simulations can reach the native state of BdpA. Consistent with experimental observations, including Φ-value analyses, formation of helix II/III hairpin was a crucial step that provides a template upon which helix I could form and the folding process could complete. Early formation of helix III was observed which is consistent with the experimental results of higher residual helical content of isolated helix III among the three helices. The calculated temperature-dependent profile and the melting temperature were in close agreement with the experimental results. The simulations further revealed that phenylalanine 31 may play critical to achieve the correct packing of the three helices which is consistent with the experimental observation

  8. Membrane binding and insertion of a pHLIP peptide studied by all-atom molecular dynamics simulations.

    PubMed

    Deng, Yonghua; Qian, Zhenyu; Luo, Yin; Zhang, Yun; Mu, Yuguang; Wei, Guanghong

    2013-07-12

    Recent experiments in function mechanism study reported that a pH low-insertion peptide (pHLIP) can insert into a zwitterionic palmitoyloleoylphosphatidylcholine (POPC) lipid bilayer at acidic pH while binding to the bilayer surface at basic pH. However, the atomic details of the pH-dependent interaction of pHLIP with a POPC bilayer are not well understood. In this study, we investigate the detailed interactions of pHLIP with a POPC bilayer at acidic and basic pH conditions as those used in function mechanism study, using all-atom molecular dynamics (MD) simulations. Simulations have been performed by employing the initial configurations, where pHLIP is placed in aqueous solution, parallel to bilayer surface (system S), partially-inserted (system P), or fully-inserted (system F) in POPC bilayers. On the basis of multiple 200-ns MD simulations, we found (1) pHLIP in system S can spontaneously insert into a POPC bilayer at acidic pH, while binding to the membrane surface at basic pH; (2) pHLIP in system P can insert deep into a POPC bilayer at acidic pH, while it has a tendency to exit, and stays at bilayer surface at basic pH; (3) pHLIP in system F keeps in an α-helical structure at acidic pH while partially unfolding at basic pH. This study provides at atomic-level the pH-induced insertion of pHLIP into POPC bilayer.

  9. Implicit Solvent Model for Million-Atom Atomistic Simulations: Insights into the Organization of 30-nm Chromatin Fiber.

    PubMed

    Izadi, Saeed; Anandakrishnan, Ramu; Onufriev, Alexey V

    2016-12-13

    Molecular dynamics (MD) simulations based on the implicit solvent generalized Born (GB) models can provide significant computational advantages over the traditional explicit solvent simulations. However, the standard GB becomes prohibitively expensive for all-atom simulations of large structures; the model scales poorly, ∼n(2), with the number of solute atoms. Here we combine our recently developed optimal point charge approximation (OPCA) with the hierarchical charge partitioning (HCP) approximation to present an ∼n log n multiscale, yet fully atomistic, GB model (GB-HCPO). The HCP approximation exploits the natural organization of biomolecules (atoms, groups, chains, and complexes) to partition the structure into multiple hierarchical levels of components. OPCA approximates the charge distribution for each of these components by a small number of point charges so that the low order multipole moments of these components are optimally reproduced. The approximate charges are then used for computing electrostatic interactions with distant components, while the full set of atomic charges are used for nearby components. We show that GB-HCPO can deliver up to 2 orders of magnitude speedup compared to the standard GB, with minimal impact on its accuracy. For large structures, GB-HCPO can approach the same nominal speed, as in nanoseconds per day, as the highly optimized explicit-solvent simulation based on particle mesh Ewald (PME). The increase in the nominal simulation speed, relative to the standard GB, coupled with substantially faster sampling of conformational space, relative to the explicit solvent, makes GB-HCPO a suitable candidate for MD simulation of large atomistic systems in implicit solvent. As a practical demonstration, we use GB-HCPO simulation to refine a ∼1.16 million atom structure of 30 nm chromatin fiber (40 nucleosomes). The refined structure suggests important details about spatial organization of the linker DNA and the histone tails in the

  10. A coarse-graining approach for molecular simulation that retains the dynamics of the all-atom reference system by implementing hydrodynamic interactions

    NASA Astrophysics Data System (ADS)

    Markutsya, Sergiy; Lamm, Monica H.

    2014-11-01

    We report on a new approach for deriving coarse-grained intermolecular forces that retains the frictional contribution that is often discarded by conventional coarse-graining methods. The approach is tested for water and an aqueous glucose solution, and the results from the new implementation for coarse-grained molecular dynamics simulation show remarkable agreement with the dynamics obtained from reference all-atom simulations. The agreement between the structural properties observed in the coarse-grained and all-atom simulations is also preserved. We discuss how this approach may be applied broadly to any existing coarse-graining method where the coarse-grained models are rigorously derived from all-atom reference systems.

  11. A coarse-graining approach for molecular simulation that retains the dynamics of the all-atom reference system by implementing hydrodynamic interactions

    SciTech Connect

    Markutsya, Sergiy; Lamm, Monica H.

    2014-11-07

    We report on a new approach for deriving coarse-grained intermolecular forces that retains the frictional contribution that is often discarded by conventional coarse-graining methods. The approach is tested for water and an aqueous glucose solution, and the results from the new implementation for coarse-grained molecular dynamics simulation show remarkable agreement with the dynamics obtained from reference all-atom simulations. The agreement between the structural properties observed in the coarse-grained and all-atom simulations is also preserved. We discuss how this approach may be applied broadly to any existing coarse-graining method where the coarse-grained models are rigorously derived from all-atom reference systems.

  12. Structure of Alzheimer's 10-35 β peptide from replica-exchange molecular dynamics simulations in explicit water

    NASA Astrophysics Data System (ADS)

    Baumketner, Andriy; Shea, Joan-Emma

    2006-03-01

    We report a replica-exchange molecular dynamics study of the 10-35 fragment of Alzheimer's disease amyloid β peptide, Aβ10-35, in aqueous solution. This fragment was previously seen [J. Str. Biol. 130 (2000) 130] to possess all the most important amyloidogenic properties characteristic of full-length Aβ peptides. Our simulations attempted to fold Aβ10-35 from first principles. The peptide was modeled using all-atom OPLS/AA force field in conjunction with the TIP3P explicit solvent model. A total of 72 replicas were considered and simulated over 40 ns of total time, including 5 ns of initial equilibration. We find that Aβ10-35 does not possess any unique folded state, a 3D structure of predominant population, under normal temperature and pressure. Rather, this peptide exists as a mixture of collapsed globular states that remain in rapid dynamic equilibrium with each other. This conformational ensemble is seen to be dominated by random coil and bend structures with insignificant presence of α-helical or β-sheet structure. We find that, overall, the 3D structure of Aβ10-35 is shaped by salt bridges formed between oppositely charged residues.Of all possible salt bridges, K28-D23 was seen to have the highest formation probability, totaling more than 60% of the time.

  13. Studies of base pair sequence effects on DNA solvation based on all-atom molecular dynamics simulations.

    PubMed

    Dixit, Surjit B; Mezei, Mihaly; Beveridge, David L

    2012-07-01

    Detailed analyses of the sequence-dependent solvation and ion atmosphere of DNA are presented based on molecular dynamics (MD) simulations on all the 136 unique tetranucleotide steps obtained by the ABC consortium using the AMBER suite of programs. Significant sequence effects on solvation and ion localization were observed in these simulations. The results were compared to essentially all known experimental data on the subject. Proximity analysis was employed to highlight the sequence dependent differences in solvation and ion localization properties in the grooves of DNA. Comparison of the MD-calculated DNA structure with canonical A- and B-forms supports the idea that the G/C-rich sequences are closer to canonical A- than B-form structures, while the reverse is true for the poly A sequences, with the exception of the alternating ATAT sequence. Analysis of hydration density maps reveals that the flexibility of solute molecule has a significant effect on the nature of observed hydration. Energetic analysis of solute-solvent interactions based on proximity analysis of solvent reveals that the GC or CG base pairs interact more strongly with water molecules in the minor groove of DNA that the AT or TA base pairs, while the interactions of the AT or TA pairs in the major groove are stronger than those of the GC or CG pairs. Computation of solvent-accessible surface area of the nucleotide units in the simulated trajectories reveals that the similarity with results derived from analysis of a database of crystallographic structures is excellent. The MD trajectories tend to follow Manning's counterion condensation theory, presenting a region of condensed counterions within a radius of about 17 A from the DNA surface independent of sequence. The GC and CG pairs tend to associate with cations in the major groove of the DNA structure to a greater extent than the AT and TA pairs. Cation association is more frequent in the minor groove of AT than the GC pairs. In general, the

  14. Pupil Dilation to Explicit and Non-Explicit Sexual Stimuli.

    PubMed

    Watts, Tuesday M; Holmes, Luke; Savin-Williams, Ritch C; Rieger, Gerulf

    2017-01-01

    Pupil dilation to explicit sexual stimuli (footage of naked and aroused men or women) can elicit sex and sexual orientation differences in sexual response. If similar patterns were replicated with non-explicit sexual stimuli (footage of dressed men and women), then pupil dilation could be indicative of automatic sexual response in fully noninvasive designs. We examined this in 325 men and women with varied sexual orientations to determine whether dilation patterns to non-explicit sexual stimuli resembled those to explicit sexual stimuli depicting the same sex or other sex. Sexual orientation differences in pupil dilation to non-explicit sexual stimuli mirrored those to explicit sexual stimuli. However, the relationship of dilation to non-explicit sexual stimuli with dilation to corresponding explicit sexual stimuli was modest, and effect magnitudes were smaller with non-explicit sexual stimuli than explicit sexual stimuli. The prediction that sexual orientation differences in pupil dilation are larger in men than in women was confirmed with explicit sexual stimuli but not with non-explicit sexual stimuli.

  15. All-atom Molecular-level Computational Simulations of Planar Longitudinal Shockwave Interactions with Polyurea, Soda-lime Glass and Polyurea/Glass Interfaces

    DTIC Science & Technology

    2014-01-01

    All-atom molecular-level computational simulations of planar longitudinal shockwave interactions with polyurea, soda-lime glass and polyurea/glass...sandwich structures under dynamic-loading conditions involving propagation of planar longitudinal shockwaves . Design/methodology/approach – The problem...of shockwave generation, propagation and interaction with material boundaries is investigated using non-equilibrium molecular dynamics. The results

  16. Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

    PubMed

    Shen, Lin; Yang, Weitao

    2016-04-12

    We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer.

  17. Reconciling structural and thermodynamic predictions using all-atom and coarse-grain force fields: the case of charged oligo-arginine translocation into DMPC bilayers.

    PubMed

    Hu, Yuan; Sinha, Sudipta Kumar; Patel, Sandeep

    2014-10-16

    Using the translocation of short, charged cationic oligo-arginine peptides (mono-, di-, and triarginine) from bulk aqueous solution into model DMPC bilayers, we explore the question of the similarity of thermodynamic and structural predictions obtained from molecular dynamics simulations using all-atom and Martini coarse-grain force fields. Specifically, we estimate potentials of mean force associated with translocation using standard all-atom (CHARMM36 lipid) and polarizable and nonpolarizable Martini force fields, as well as a series of modified Martini-based parameter sets. We find that we are able to reproduce qualitative features of potentials of mean force of single amino acid side chain analogues into model bilayers. In particular, modifications of peptide-water and peptide-membrane interactions allow prediction of free energy minima at the bilayer-water interface as obtained with all-atom force fields. In the case of oligo-arginine peptides, the modified parameter sets predict interfacial free energy minima as well as free energy barriers in almost quantitative agreement with all-atom force field based simulations. Interfacial free energy minima predicted by a modified coarse-grained parameter set are -2.51, -4.28, and -5.42 for mono-, di-, and triarginine; corresponding values from all-atom simulations are -0.83, -3.33, and -3.29, respectively, all in units of kcal/mol. We found that a stronger interaction between oligo-arginine and the membrane components and a weaker interaction between oligo-arginine and water are crucial for producing such minima in PMFs using the polarizable CG model. The difference between bulk aqueous and bilayer center states predicted by the modified coarse-grain force field are 11.71, 14.14, and 16.53 kcal/mol, and those by the all-atom model are 6.94, 8.64, and 12.80 kcal/mol; those are of almost the same order of magnitude. Our simulations also demonstrate a remarkable similarity in the structural aspects of the ensemble of

  18. Reconciling Structural and Thermodynamic Predictions Using All-Atom and Coarse-Grain Force Fields: The Case of Charged Oligo-Arginine Translocation into DMPC Bilayers

    PubMed Central

    2015-01-01

    Using the translocation of short, charged cationic oligo-arginine peptides (mono-, di-, and triarginine) from bulk aqueous solution into model DMPC bilayers, we explore the question of the similarity of thermodynamic and structural predictions obtained from molecular dynamics simulations using all-atom and Martini coarse-grain force fields. Specifically, we estimate potentials of mean force associated with translocation using standard all-atom (CHARMM36 lipid) and polarizable and nonpolarizable Martini force fields, as well as a series of modified Martini-based parameter sets. We find that we are able to reproduce qualitative features of potentials of mean force of single amino acid side chain analogues into model bilayers. In particular, modifications of peptide–water and peptide–membrane interactions allow prediction of free energy minima at the bilayer–water interface as obtained with all-atom force fields. In the case of oligo-arginine peptides, the modified parameter sets predict interfacial free energy minima as well as free energy barriers in almost quantitative agreement with all-atom force field based simulations. Interfacial free energy minima predicted by a modified coarse-grained parameter set are −2.51, −4.28, and −5.42 for mono-, di-, and triarginine; corresponding values from all-atom simulations are −0.83, −3.33, and −3.29, respectively, all in units of kcal/mol. We found that a stronger interaction between oligo-arginine and the membrane components and a weaker interaction between oligo-arginine and water are crucial for producing such minima in PMFs using the polarizable CG model. The difference between bulk aqueous and bilayer center states predicted by the modified coarse-grain force field are 11.71, 14.14, and 16.53 kcal/mol, and those by the all-atom model are 6.94, 8.64, and 12.80 kcal/mol; those are of almost the same order of magnitude. Our simulations also demonstrate a remarkable similarity in the structural aspects of

  19. Probing the global and local dynamics of aminoacyl-tRNA synthetases using all-atom and coarse-grained simulations.

    PubMed

    Strom, Alexander M; Fehling, Samuel C; Bhattacharyya, Sudeep; Hati, Sanchita

    2014-05-01

    Coarse-grained simulations have emerged as invaluable tools for studying conformational changes in biomolecules. To evaluate the effectiveness of computationally inexpensive coarse-grained models in studying global and local dynamics of large protein systems like aminoacyl-tRNA synthetases, we have performed coarse-grained normal mode analysis, as well as principle component analysis on trajectories of all-atom and coarse-grained molecular dynamics simulations for three aminoacyl-tRNA synthetases--Escherichia coli methionyl-tRNA synthetase, Thermus thermophilus leucyl-tRNA synthetase, and Enterococcus faecium prolyl-tRNA synthetase. In the present study, comparison of predicted dynamics based on B-factor and overlap calculations revealed that coarse-grained methods are comparable to the all-atom simulations in depicting the intrinsic global dynamics of the three enzymes. However, the principal component analyses of the motions obtained from the all-atom molecular dynamics simulations provide a superior description of the local fluctuations of these enzymes. In particular, the all-atom model was able to capture the functionally relevant substrate-induced dynamical changes in prolyl-tRNA synthetase. The alteration in the coupled dynamics between the catalytically important proline-binding loop and its neighboring structural elements due to substrate binding has been characterized and reported for the first time. Taken together, the study portrays comparable and contrasting situations in studying the functional dynamics of large multi-domain aminoacyl-tRNA synthetases using coarse-grained and all-atom simulation methods.

  20. What Should Be Explicit in Explicit Grammar Instruction?

    ERIC Educational Resources Information Center

    Nagai, Noriko; Ayano, Seiki; Okada, Keiko; Nakanishi, Takayuki

    2015-01-01

    This article proposes an approach to explicit grammar instruction that seeks to develop metalinguistic knowledge of the L2 and raise L2 learners' awareness of their L1, which is crucial for the success of second language acquisition (Ellis 1997, 2002). If explicit instruction is more effective than implicit instruction (Norris and Ortega 2000),…

  1. An FFT-based method for modeling protein folding and binding under crowding: benchmarking on ellipsoidal and all-atom crowders

    PubMed Central

    Qin, Sanbo; Zhou, Huan-Xiang

    2013-01-01

    It is now well recognized that macromolecular crowding can exert significant effects on protein folding and binding stability. In order to calculate such effects in direct simulations of proteins mixed with bystander macromolecules, the latter (referred to as crowders) are usually modeled as spheres and the proteins represented at a coarse-grained level. Our recently developed postprocessing approach allows the proteins to be represented at the all-atom level but, for computational efficiency, has only been implemented for spherical crowders. Modeling crowder molecules in cellular environments and in vitro experiments as spheres may distort their effects on protein stability. Here we present a new method that is capable for treating aspherical crowders. The idea, borrowed from protein-protein docking, is to calculate the excess chemical potential of the proteins in crowded solution by fast Fourier transform (FFT). As the first application, we studied the effects of ellipsoidal crowders on the folding and binding free energies of all-atom proteins, and found, in agreement with previous direct simulations with coarse-grained protein models, that the aspherical crowders exert greater stabilization effects than spherical crowders of the same volume. Moreover, as demonstrated here, the FFT-based method has the important property that its computational cost does not increase strongly even when the level of details in representing the crowders is increased all the way to all-atom, thus significantly accelerating realistic modeling of protein folding and binding in cell-like environments. PMID:24187527

  2. Significant reduction in errors associated with nonbonded contacts in protein crystal structures: automated all-atom refinement with PrimeX.

    PubMed

    Bell, Jeffrey A; Ho, Kenneth L; Farid, Ramy

    2012-08-01

    All-atom models are essential for many applications in molecular modeling and computational chemistry. Nonbonded atomic contacts much closer than the sum of the van der Waals radii of the two atoms (clashes) are commonly observed in such models derived from protein crystal structures. A set of 94 recently deposited protein structures in the resolution range 1.5-2.8 Å were analyzed for clashes by the addition of all H atoms to the models followed by optimization and energy minimization of the positions of just these H atoms. The results were compared with the same set of structures after automated all-atom refinement with PrimeX and with nonbonded contacts in protein crystal structures at a resolution equal to or better than 0.9 Å. The additional PrimeX refinement produced structures with reasonable summary geometric statistics and similar R(free) values to the original structures. The frequency of clashes at less than 0.8 times the sum of van der Waals radii was reduced over fourfold compared with that found in the original structures, to a level approaching that found in the ultrahigh-resolution structures. Moreover, severe clashes at less than or equal to 0.7 times the sum of atomic radii were reduced 15-fold. All-atom refinement with PrimeX produced improved crystal structure models with respect to nonbonded contacts and yielded changes in structural details that dramatically impacted on the interpretation of some protein-ligand interactions.

  3. An FFT-based method for modeling protein folding and binding under crowding: benchmarking on ellipsoidal and all-atom crowders.

    PubMed

    Qin, Sanbo; Zhou, Huan-Xiang

    2013-10-01

    It is now well recognized that macromolecular crowding can exert significant effects on protein folding and binding stability. In order to calculate such effects in direct simulations of proteins mixed with bystander macromolecules, the latter (referred to as crowders) are usually modeled as spheres and the proteins represented at a coarse-grained level. Our recently developed postprocessing approach allows the proteins to be represented at the all-atom level but, for computational efficiency, has only been implemented for spherical crowders. Modeling crowder molecules in cellular environments and in vitro experiments as spheres may distort their effects on protein stability. Here we present a new method that is capable for treating aspherical crowders. The idea, borrowed from protein-protein docking, is to calculate the excess chemical potential of the proteins in crowded solution by fast Fourier transform (FFT). As the first application, we studied the effects of ellipsoidal crowders on the folding and binding free energies of all-atom proteins, and found, in agreement with previous direct simulations with coarse-grained protein models, that the aspherical crowders exert greater stabilization effects than spherical crowders of the same volume. Moreover, as demonstrated here, the FFT-based method has the important property that its computational cost does not increase strongly even when the level of details in representing the crowders is increased all the way to all-atom, thus significantly accelerating realistic modeling of protein folding and binding in cell-like environments.

  4. All-atom molecular dynamics study of a spherical micelle composed of N-acetylated poly(ethylene glycol)-poly(gamma-benzyl L-glutamate) block copolymers: a potential carrier of drug delivery systems for cancer.

    PubMed

    Kuramochi, Hiroshi; Andoh, Yoshimichi; Yoshii, Noriyuki; Okazaki, Susumu

    2009-11-19

    An all-atom molecular dynamics simulation of a spherical micelle composed of amphiphilic N-acetylated poly(ethylene glycol)-poly(gamma-benzyl L-glutamate) (PEG-PBLG-Ac) block copolymers was performed in aqueous solution at 298.15 K and 1 atm. Such copolymers have received considerable attention as carriers in drug delivery systems. In this study, we used copolymers consisting of 11 EG units and 9 BLG units as models. Starting from the copolymers arranged spherically, the calculation predicted an equilibrium state consisting of a slightly elliptical micelle structure with a hydrophobic PBLG inner core and a hydrophilic PEG outer shell. The micelle structure was dynamically stable during the simulation, with the PEG blocks showing a compact helical conformation and the PBLG blocks an alpha-helix form. Multiple hydrogen bonds with solvent water molecules stabilized the helical conformation of the PEG blocks, leading to their hydration as shown by longer residence times of water molecules near the PEG ether oxygen atoms compared with that of bulk water. Some water molecules have also been found distributed within the hydrophobic core; they showed continuous exchange with bulk water during the simulation. Those molecules existed mostly as a cluster in spaces between the copolymers, forming hydrogen bonds among themselves as well as with the hydrophobic core through hydrophilic groups such as esters and amides. The water molecules forming hydrogen bonds with the micelle may play an important role in the stabilization of the micelle structure.

  5. The Explicit Teaching of Reading.

    ERIC Educational Resources Information Center

    Hancock, Joelie, Ed.

    Exploring the explicit teaching of reading, this book is the result of a group of Australian teachers who took a closer look at their teaching so that they could be clearer to their kindergarten through middle-school students. Chapter 1 is based on a presentation at a Saturday inservice program on explicit teaching. Chapters 2-9 were written by…

  6. Testing the semi-explicit assembly solvation model in the SAMPL3 community blind test

    NASA Astrophysics Data System (ADS)

    Kehoe, Charles W.; Fennell, Christopher J.; Dill, Ken A.

    2012-05-01

    We report here a test of the Semi-Explicit Assembly (SEA) model in the solvation free energy category of the SAMPL3 blind prediction event (summer 2011). We tested how dependent the SEA results are on the chosen force field by performing calculations with both the General Amber and OPLS force fields. We compared our SEA results with full molecular dynamics simulations in explicit solvent. Of the 20 submissions, our SEA/OPLS results gave the second smallest RMS errors in free energies compared to experiments. SEA gives results that are very similar to those of its underlying force field and explicit solvent model. Hence, while the SEA water modeling approach is much faster than explicit solvent simulations, its predictions appear to be just as accurate.

  7. Probing the folded state and mechanical unfolding pathways of T4 lysozyme using all-atom and coarse-grained molecular simulation.

    PubMed

    Zheng, Wenjun; Glenn, Paul

    2015-01-21

    The Bacteriophage T4 Lysozyme (T4L) is a prototype modular protein comprised of an N-terminal and a C-domain domain, which was extensively studied to understand the folding/unfolding mechanism of modular proteins. To offer detailed structural and dynamic insights to the folded-state stability and the mechanical unfolding behaviors of T4L, we have performed extensive equilibrium and steered molecular dynamics simulations of both the wild-type (WT) and a circular permutation (CP) variant of T4L using all-atom and coarse-grained force fields. Our all-atom and coarse-grained simulations of the folded state have consistently found greater stability of the C-domain than the N-domain in isolation, which is in agreement with past thermostatic studies of T4L. While the all-atom simulation cannot fully explain the mechanical unfolding behaviors of the WT and the CP variant observed in an optical tweezers study, the coarse-grained simulations based on the Go model or a modified elastic network model (mENM) are in qualitative agreement with the experimental finding of greater unfolding cooperativity in the WT than the CP variant. Interestingly, the two coarse-grained models predict different structural mechanisms for the observed change in cooperativity between the WT and the CP variant--while the Go model predicts minor modification of the unfolding pathways by circular permutation (i.e., preserving the general order that the N-domain unfolds before the C-domain), the mENM predicts a dramatic change in unfolding pathways (e.g., different order of N/C-domain unfolding in the WT and the CP variant). Based on our simulations, we have analyzed the limitations of and the key differences between these models and offered testable predictions for future experiments to resolve the structural mechanism for cooperative folding/unfolding of T4L.

  8. Probing the folded state and mechanical unfolding pathways of T4 lysozyme using all-atom and coarse-grained molecular simulation

    NASA Astrophysics Data System (ADS)

    Zheng, Wenjun; Glenn, Paul

    2015-01-01

    The Bacteriophage T4 Lysozyme (T4L) is a prototype modular protein comprised of an N-terminal and a C-domain domain, which was extensively studied to understand the folding/unfolding mechanism of modular proteins. To offer detailed structural and dynamic insights to the folded-state stability and the mechanical unfolding behaviors of T4L, we have performed extensive equilibrium and steered molecular dynamics simulations of both the wild-type (WT) and a circular permutation (CP) variant of T4L using all-atom and coarse-grained force fields. Our all-atom and coarse-grained simulations of the folded state have consistently found greater stability of the C-domain than the N-domain in isolation, which is in agreement with past thermostatic studies of T4L. While the all-atom simulation cannot fully explain the mechanical unfolding behaviors of the WT and the CP variant observed in an optical tweezers study, the coarse-grained simulations based on the Go model or a modified elastic network model (mENM) are in qualitative agreement with the experimental finding of greater unfolding cooperativity in the WT than the CP variant. Interestingly, the two coarse-grained models predict different structural mechanisms for the observed change in cooperativity between the WT and the CP variant—while the Go model predicts minor modification of the unfolding pathways by circular permutation (i.e., preserving the general order that the N-domain unfolds before the C-domain), the mENM predicts a dramatic change in unfolding pathways (e.g., different order of N/C-domain unfolding in the WT and the CP variant). Based on our simulations, we have analyzed the limitations of and the key differences between these models and offered testable predictions for future experiments to resolve the structural mechanism for cooperative folding/unfolding of T4L.

  9. Probing the folded state and mechanical unfolding pathways of T4 lysozyme using all-atom and coarse-grained molecular simulation

    SciTech Connect

    Zheng, Wenjun Glenn, Paul

    2015-01-21

    The Bacteriophage T4 Lysozyme (T4L) is a prototype modular protein comprised of an N-terminal and a C-domain domain, which was extensively studied to understand the folding/unfolding mechanism of modular proteins. To offer detailed structural and dynamic insights to the folded-state stability and the mechanical unfolding behaviors of T4L, we have performed extensive equilibrium and steered molecular dynamics simulations of both the wild-type (WT) and a circular permutation (CP) variant of T4L using all-atom and coarse-grained force fields. Our all-atom and coarse-grained simulations of the folded state have consistently found greater stability of the C-domain than the N-domain in isolation, which is in agreement with past thermostatic studies of T4L. While the all-atom simulation cannot fully explain the mechanical unfolding behaviors of the WT and the CP variant observed in an optical tweezers study, the coarse-grained simulations based on the Go model or a modified elastic network model (mENM) are in qualitative agreement with the experimental finding of greater unfolding cooperativity in the WT than the CP variant. Interestingly, the two coarse-grained models predict different structural mechanisms for the observed change in cooperativity between the WT and the CP variant—while the Go model predicts minor modification of the unfolding pathways by circular permutation (i.e., preserving the general order that the N-domain unfolds before the C-domain), the mENM predicts a dramatic change in unfolding pathways (e.g., different order of N/C-domain unfolding in the WT and the CP variant). Based on our simulations, we have analyzed the limitations of and the key differences between these models and offered testable predictions for future experiments to resolve the structural mechanism for cooperative folding/unfolding of T4L.

  10. Explicit Substitutions and All That

    NASA Technical Reports Server (NTRS)

    Ayala-Rincon, Mauricio; Munoz, Cesar; Busnell, Dennis M. (Technical Monitor)

    2000-01-01

    Explicit substitution calculi are extensions of the Lambda-calculus where the substitution mechanism is internalized into the theory. This feature makes them suitable for implementation and theoretical study of logic-based tools such as strongly typed programming languages and proof assistant systems. In this paper we explore new developments on two of the most successful styles of explicit substitution calculi: the lambda(sigma)- and lambda(s(e))-calculi.

  11. Explicit Substitutions and All That

    NASA Technical Reports Server (NTRS)

    Ayala-Rincon, Mauricio; Munoz, Cesar

    2000-01-01

    Explicit substitution calculi are extensions of the lambda-calculus where the substitution mechanism is internalized into the theory. This feature makes them suitable for implementation and theoretical study of logic-based tools such as strongly typed programming languages and proof assistant systems. In this paper we explore new developments on two of the most successful styles of explicit substitution calculi: the lambda sigma- and lambda S(e)-calculi.

  12. Solvent induced conformational fluctuation of alanine dipeptide studied by using vibrational probes

    NASA Astrophysics Data System (ADS)

    Cai, Kaicong; Du, Fenfen; Liu, Jia; Su, Tingting

    2015-02-01

    The solvation effect on the three dimensional structure and the vibrational feature of alanine dipeptide (ALAD) was evaluated by applying the implicit solvents from polarizable continuum solvent model (PCM) through ab initio calculations, by using molecular dynamic (MD) simulations with explicit solvents, and by combining these two approaches. The implicit solvent induced potential energy fluctuations of ALAD in CHCl3, DMSO and H2O are revealed by means of ab initio calculations, and a global view of conformational and solvation environmental dependence of amide I frequencies is achieved. The results from MD simulations with explicit solvents show that ALAD trends to form PPII, αL, αR, and C5 in water, PPII and C5 in DMSO, and C5 in CHCl3, ordered by population, and the demonstration of the solvated structure, the solute-solvent interaction and hydrogen bonding is therefore enhanced. Representative ALAD-solvent clusters were sampled from MD trajectories and undergone ab initio calculations. The explicit solvents reveal the hydrogen bonding between ALAD and solvents, and the correlation between amide I frequencies and the Cdbnd O bond length is built. The implicit solvents applied to the ALAD-solvent clusters further compensate the solvation effect from the bulk, and thus enlarge the degree of structural distortion and the amide I frequency red shift. The combination of explicit solvent in the first hydration shell and implicit solvent in the bulk is helpful for our understanding about the conformational fluctuation of solvated polypeptides through vibrational probes.

  13. Solvent induced conformational fluctuation of alanine dipeptide studied by using vibrational probes.

    PubMed

    Cai, Kaicong; Du, Fenfen; Liu, Jia; Su, Tingting

    2015-02-25

    The solvation effect on the three dimensional structure and the vibrational feature of alanine dipeptide (ALAD) was evaluated by applying the implicit solvents from polarizable continuum solvent model (PCM) through ab initio calculations, by using molecular dynamic (MD) simulations with explicit solvents, and by combining these two approaches. The implicit solvent induced potential energy fluctuations of ALAD in CHCl3, DMSO and H2O are revealed by means of ab initio calculations, and a global view of conformational and solvation environmental dependence of amide I frequencies is achieved. The results from MD simulations with explicit solvents show that ALAD trends to form PPII, αL, αR, and C5 in water, PPII and C5 in DMSO, and C5 in CHCl3, ordered by population, and the demonstration of the solvated structure, the solute-solvent interaction and hydrogen bonding is therefore enhanced. Representative ALAD-solvent clusters were sampled from MD trajectories and undergone ab initio calculations. The explicit solvents reveal the hydrogen bonding between ALAD and solvents, and the correlation between amide I frequencies and the CO bond length is built. The implicit solvents applied to the ALAD-solvent clusters further compensate the solvation effect from the bulk, and thus enlarge the degree of structural distortion and the amide I frequency red shift. The combination of explicit solvent in the first hydration shell and implicit solvent in the bulk is helpful for our understanding about the conformational fluctuation of solvated polypeptides through vibrational probes.

  14. Molecular dynamics study of human carbonic anhydrase II in complex with Zn(2+) and acetazolamide on the basis of all-atom force field simulations.

    PubMed

    Wambo, Thierry O; Chen, Liao Y; McHardy, Stanton F; Tsin, Andrew T

    2016-01-01

    Human carbonic anhydrase II (hCAII) represents an ultimate example of the perfectly efficient metalloenzymes, which is capable of catalyzing the hydration of carbon dioxide with a rate approaching the diffusion controlled limit. Extensive experimental studies of this physiologically important metalloprotein have been done to elucidate the fundamentals of its enzymatic actions: what residues anchor the Zn(2+) (or another divalent cation) at the bottom of the binding pocket; how the relevant residues work concertedly with the divalent cation in the reversible conversions between CO2 and HCO3(-); what are the protonation states of the relevant residues and acetazolamide, an inhibitor complexed with hCAII, etc. In this article, we present a detailed computational study on the basis of the all-atom CHARMM force field where Zn(2+) is represented with a simple model of divalent cation using the transferrable parameters available from the current literature. We compute the hydration free energy of Zn(2+), the characteristics of hCAII-Zn(2+) complexation, and the absolute free energy of binding acetazolamide to the hCAII-Zn(2+) complex. In each of these three problems, our computed results agree with the experimental data within the known margin of error without making any case-by-case adjustments to the parameters. The quantitatively accurate insights we gain in this all-atom molecular dynamics study should be helpful in the search and design of more specific inhibitors of this and other carbonic anhydrases.

  15. Insight into the Properties of Cardiolipin Containing Bilayers from Molecular Dynamics Simulations, Using a Hybrid All-Atom/United-Atom Force Field.

    PubMed

    Aguayo, Daniel; González-Nilo, Fernando D; Chipot, Christophe

    2012-05-08

    Simulation of three models of cardiolipin (CL) containing membranes using a new set of parameters for tetramyristoyl and tetraoleoyl CLs has been developed in the framework of the united-atom CHARMM27-UA and the all-atom CHARMM36 force fields with the aim of performing molecular dynamics (MD) simulations of cardiolipin-containing mixed-lipid membranes. The new parameters use a hybrid representation of all-atom head groups in conjunction with implicit-hydrogen united-atom (UA) to describe the oleoyl and myristoyl chains of the CLs, in lieu of the fully atomistic description, thereby allowing longer simulations to be undertaken. The physicochemical properties of the bilayers were determined and compared with previously reported data. Furthermore, using tetramyristoyl CL mixed with POPG and POPE lipids, a mitochondrial membrane was simulated. The results presented here show the different behavior of the bilayers as a result of the lipid composition, where the length of the acyl chain and the conformation of the headgroup can be associated with the mitochondrial membrane properties. The new hybrid CL parameters prove to be well suited for the simulation of the molecular structure of CL-containing bilayers and can be extended to other lipid bilayers composed of CLs with different acyl chains or alternate head groups.

  16. Coulombic free energy and salt ion association per phosphate of all-atom models of DNA oligomer: dependence on oligomer size.

    PubMed

    Shkel, Irina A; Record, M Thomas

    2012-08-23

    We investigate how the coulombic Gibbs free energy and salt ion association per phosphate charge of DNA oligomers vary with oligomer size (i.e. number of charged residues ∣ZD∣) at 0.15 M univalent salt by non-linear Poisson Boltzmann (NLPB) analysis of all-atom DNA models. Calculations of these quantities ([Formula: see text], [Formula: see text]) are performed for short and long double-stranded (ds) and single-stranded (ss) DNA oligomers, ranging from 4 to 118 phosphates (ds) and from 2 to 59 phosphates (ss). Behaviors of [Formula: see text] and [Formula: see text] as functions of ∣ZD∣ provide a measure of the range of the coulombic end effect and determine the size of an oligomer at which an interior region with the properties (per charge) of the infinite-length polyelectrolyte first appears. This size (10-11 phosphates at each end for ds DNA and 6-9 for ss DNA at 0.15 M salt) is in close agreement with values obtained previously by Monte Carlo and NLPB calculations for cylindrical models of polyions, and by analysis of binding of oligocations to DNA oligomers. Differences in [Formula: see text] and in [Formula: see text] between ss and ds DNA are used to predict effects of oligomeric size and salt concentration on duplex stability in the vicinity of 0.15 M salt. Results of all-atom calculations are compared with results of less structurally detailed models and with experimental data.

  17. All-atom ab initio native structure prediction of a mixed fold (1FME): a comparison of structural and folding characteristics of various beta beta alpha miniproteins.

    PubMed

    Kim, Eunae; Jang, Soonmin; Pak, Youngshang

    2009-11-21

    We performed an all-atom ab initio native structure prediction of 1FME, which is one of the computationally challenging mixed fold beta beta alpha miniproteins, by combining a novel conformational search algorithm (multiplexed Q-replica exchange molecular dynamics scheme) with a well-balanced all-atom force field employing a generalized Born implicit solvation model (param99MOD5/GBSA). The nativelike structure of 1FME was identified from the lowest free energy minimum state and in excellent agreement with the NMR structure. Based on the interpretation of the free energy landscape, the structural properties as well as the folding behaviors of 1FME were compared with other beta beta alpha miniproteins (1FSD, 1PSV, and BBA5) that we have previously studied with the same force field. Our simulation showed that the 28-residue beta beta alpha miniproteins (1FME, 1FSD, and 1PSV) share a common feature of the free energy topography and exhibit the three local minimum states on each computed free energy map, but the 23-residue miniprotein (BBA5) follows a downhill folding with a single minimum state. Also, the structure and stability changes resulting from the two point mutation (Gln1-->Glu1 and Ile7-->Tyr7) of 1FSD were investigated in details for direct comparison with the experiment. The comparison shows that upon mutation, the experimentally observed turn type switch from an irregular turn (1FSD) to type I(') turn (1FME) was well reproduced with the present simulation.

  18. Stoddard solvent poisoning

    MedlinePlus

    These products contain Stoddard solvent: Dry cleaning fluids Paints Paint thinner Stoddard solvent ( mineral spirits ) Toners used in copy machines This list may not include all products containing Stoddard solvent.

  19. Phase behavior of a lattice hydrophobic oligomer in explicit water.

    PubMed

    Romero-Vargas Castrillón, Santiago; Matysiak, Silvina; Stillinger, Frank H; Rossky, Peter J; Debenedetti, Pablo G

    2012-08-09

    We investigate the thermodynamics of hydrophobic oligomer collapse using a water-explicit, three-dimensional lattice model. The model captures several aspects of protein thermodynamics, including the emergence of cold- and thermal-unfolding, as well as unfolding at high solvent density (a phenomenon akin to pressure-induced denaturation). We show that over a range of conditions spanning a ≈14% increase in solvent density, the oligomer transforms into a compact, strongly water-penetrated conformation at low temperature. This contrasts with thermal unfolding at high temperature, where the system "denatures" into an extended random coil conformation. We report a phase diagram for hydrophobic collapse that correctly captures qualitative aspects of cold and thermal unfolding at low to intermediate solvent densities.

  20. All-atom molecular dynamics study of EAK16 peptide: the effect of pH on single-chain conformation, dimerization and self-assembly behavior.

    PubMed

    Emamyari, Soheila; Fazli, Hossein

    2014-05-01

    Single-chain equilibrium conformation and dimerization of the three types of ionic EAK16 peptide are studied under three pH conditions using all-atom molecular dynamics simulations. It is found that both the single-chain conformation and the dimerization process of EAK16-IV are considerably different from those of the two other types, EAK16-I and EAK16-II. The value of pH is found to have a stronger effect on the single-chain conformation and dimerization of EAK16-IV. It is shown that in addition to the charge pattern on the peptide chains, the size of the side chains of the charged amino acids plays role in the conformation of the peptide chains and their dimerization. The results shed light on the pH-dependent self-assembly behavior of EAK16 peptide in the bulk solution, which has been reported in the literature.

  1. Calculation of the water-cyclohexane transfer free energies of neutral amino acid side-chain analogs using the OPLS all-atom force field.

    PubMed

    MacCallum, Justin L; Tieleman, D Peter

    2003-11-30

    We calculated the free energy of solvation of the neutral analogs of 18 amino acid side-chains (not including glycine and proline) using the OPLS all-atom force field in TIP4P water, SPC water, and cyclohexane by molecular dynamics simulation and thermodynamic integration. The average unsigned errors in the free energies of solvation in TIP4P, SPC, and cyclohexane are 4.4, 4.9, and 2.1 kJ/mol respectively. Most of the calculated hydration free energies are not favorable enough compared to experiment. The largest errors are found for tryptophan, histidine, glutamic acid, and glutamine. The average unsigned errors in the free energy of transfer from TIP4P to cyclohexane and from SPC to cyclohexane are 4.0 and 4.1 kJ/mol, respectively. The largest errors, of more than 7.5 kJ/mol, are found for histidine, glutamine, and glutamatic acid.

  2. An all-atom model of the chromatin fiber containing linker histones reveals a versatile structure tuned by the nucleosomal repeat length.

    PubMed

    Wong, Hua; Victor, Jean-Marc; Mozziconacci, Julien

    2007-09-12

    In the nucleus of eukaryotic cells, histone proteins organize the linear genome into a functional and hierarchical architecture. In this paper, we use the crystal structures of the nucleosome core particle, B-DNA and the globular domain of H5 linker histone to build the first all-atom model of compact chromatin fibers. In this 3D jigsaw puzzle, DNA bending is achieved by solving an inverse kinematics problem. Our model is based on recent electron microscopy measurements of reconstituted fiber dimensions. Strikingly, we find that the chromatin fiber containing linker histones is a polymorphic structure. We show that different fiber conformations are obtained by tuning the linker histone orientation at the nucleosomes entry/exit according to the nucleosomal repeat length. We propose that the observed in vivo quantization of nucleosomal repeat length could reflect nature's ability to use the DNA molecule's helical geometry in order to give chromatin versatile topological and mechanical properties.

  3. Solvent wash solution

    DOEpatents

    Neace, J.C.

    1984-03-13

    A process is claimed for removing diluent degradation products from a solvent extraction solution, which has been used to recover uranium and plutonium from spent nuclear fuel. A wash solution and the solvent extraction solution are combined. The wash solution contains (a) water and (b) up to about, and including, 50 vol % of at least one-polar water-miscible organic solvent based on the total volume of the water and the highly-polar organic solvent. The wash solution also preferably contains at least one inorganic salt. The diluent degradation products dissolve in the highly-polar organic solvent and the organic solvent extraction solvent do not dissolve in the highly-polar organic solvent. The highly-polar organic solvent and the extraction solvent are separated.

  4. Solvent wash solution

    DOEpatents

    Neace, James C.

    1986-01-01

    Process for removing diluent degradation products from a solvent extraction solution, which has been used to recover uranium and plutonium from spent nuclear fuel. A wash solution and the solvent extraction solution are combined. The wash solution contains (a) water and (b) up to about, and including, 50 volume percent of at least one-polar water-miscible organic solvent based on the total volume of the water and the highly-polar organic solvent. The wash solution also preferably contains at least one inorganic salt. The diluent degradation products dissolve in the highly-polar organic solvent and the organic solvent extraction solvent do not dissolve in the highly-polar organic solvent. The highly-polar organic solvent and the extraction solvent are separated.

  5. Simulations of solvation free energies and solubilities in supercritical solvents

    NASA Astrophysics Data System (ADS)

    Su, Zemin; Maroncelli, Mark

    2006-04-01

    Computer simulations are used to study solvation free energies and solubilities in supercritical solvents. Solvation free energies are calculated using the particle insertion method. The equilibrium solvent configurations required for these calculations are based on molecular dynamics simulations employing model solvent potentials previously tuned to reproduce liquid-vapor coexistence properties of the fluids Xe, C2H6, CO2, and CHF3. Solutes are represented by all-atom potentials based on ab initio calculations and the OPLS-AA parameter set. Without any tuning of the intermolecular potentials, such calculations are found to reproduce the solvation free energies of a variety of typical solid solutes with an average accuracy of ±2kJ /mol. Further calculations on simple model solutes are also used to explore general aspects of solvation free energies in supercritical solvents. Comparisons of solutes in Lennard-Jones and hard-sphere representations of Xe show that solvation free energies and thus solubilities are not significantly influenced by solvent density fluctuations near the critical point. The solvation enthalpy and entropy do couple to these fluctuations and diverge similarly to solute partial molar volumes. Solvation free energies are also found to be little affected by the local density augmentation characteristic of the compressible regime. In contrast to solute-solvent interaction energies, which often provide a direct measure of local solvent densities, solvation free energies are remarkably insensitive to the presence of local density augmentation.

  6. Simulations of peptide-graphene interactions in explicit water.

    PubMed

    Camden, Aerial N; Barr, Stephen A; Berry, Rajiv J

    2013-09-19

    The interaction of graphene with biomolecules has a variety of useful applications. In particular, graphitic surfaces decorated with peptides are being considered for high performance biochemical sensors. The interaction of peptides with graphene can also provide insight into the binding behavior of larger biomolecules. In this investigation, we have computed the binding enthalpies of a series of GXG tripeptides with graphene using classical molecular dynamics. Explicit water molecules were included to capture the effect of solvent. Of the twenty amino acid residues examined (X in GXG), arginine, glutamine, and asparagine exhibit the strongest interactions with graphene. Analysis of the trajectories shows that the presence of graphene affects the peptide conformation relative to its conformation in solution. We also find that the peptides favor the graphene interface predominantly due to the influence of the solvent, with hydrophilic residues binding more strongly than hydrophobic residues. These results demonstrate the need to include explicit solvent atoms when modeling peptide-graphene systems to mimic experimental conditions. Furthermore, the scheme outlined herein may be widely applicable for the determination and validation of surface interaction parameters for a host of molecular fragments using a variety of techniques, ranging from coarse-grained models to quantum mechanical methods.

  7. Toward a Coarse Graining/All Atoms Force Field (CG/AA) from a Multiscale Optimization Method: An Application to the MCM-41 Mesoporous Silicates.

    PubMed

    Ghoufi, A; Morineau, D; Lefort, R; Malfreyt, P

    2010-10-12

    Many interesting physical phenomena occur on length and time scales that are not accessible by atomistic molecular simulations. By introducing a coarse graining of the degrees of freedom, coarse-grained (CG) models allow ther study of larger scale systems for longer times. Coarse-grained force fields have been mostly derived for large molecules, including polymeric materials and proteins. By contrast, there exist no satisfactory CG potentials for mesostructured porous solid materials in the literature. This issue has become critical among a growing number of studies on confinement effects on fluid properties, which require both long time and large scale simulations and the conservation of a sufficient level of atomistic description to account for interfacial phenomena. In this paper, we present a general multiscale procedure to derive a hybrid coarse grained/all atoms force field CG/AA model for mesoporous systems. The method is applied to mesostructured MCM-41 molecular sieves, while the parameters of the mesoscopic interaction potentials are obtained and validated from the computation of the adsorption isotherm of methanol by grand canonical molecular dynamic simulation.

  8. C6 Coefficients and Dipole Polarizabilities for All Atoms and Many Ions in Rows 1-6 of the Periodic Table.

    PubMed

    Gould, Tim; Bučko, Tomáš

    2016-08-09

    Using time-dependent density functional theory (TDDFT) with exchange kernels, we calculate and test imaginary frequency-dependent dipole polarizabilities for all atoms and many ions in rows 1-6 of the periodic table. These are then integrated over frequency to produce C6 coefficients. Results are presented under different models: straight TDDFT calculations using two different kernels; "benchmark" TDDFT calculations corrected by more accurate quantum chemical and experimental data; and "benchmark" TDDFT with frozen orbital anions. Parametrizations are presented for 411+ atoms and ions, allowing results to be easily used by other researchers. A curious relationship, C6,XY ∝ [αX(0)αY(0)](0.73), is found between C6 coefficients and static polarizabilities α(0). The relationship C6,XY = 2C6,XC6,Y/[(αX/αY)C6,Y + (αY/αX)C6,X] is tested and found to work well (<5% errors) in ∼80% of the cases, but can break down badly (>30% errors) in a small fraction of cases.

  9. All-atom simulations and free-energy calculations of coiled-coil peptides with lipid bilayers: binding strength, structural transition, and effect on lipid dynamics

    PubMed Central

    Woo, Sun Young; Lee, Hwankyu

    2016-01-01

    Peptides E and K, which are synthetic coiled-coil peptides for membrane fusion, were simulated with lipid bilayers composed of lipids and cholesterols at different ratios using all-atom models. We first calculated free energies of binding from umbrella sampling simulations, showing that both E and K peptides tend to adsorb onto the bilayer surface, which occurs more strongly in the bilayer composed of smaller lipid headgroups. Then, unrestrained simulations show that K peptides more deeply insert into the bilayer with partially retaining the helical structure, while E peptides less insert and predominantly become random coils, indicating the structural transition from helices to random coils, in quantitative agreement with experiments. This is because K peptides electrostatically interact with lipid phosphates, as well as because hydrocarbons of lysines of K peptide are longer than those of glutamic acids of E peptide and thus form stronger hydrophobic interactions with lipid tails. This deeper insertion of K peptide increases the bilayer dynamics and a vacancy below the peptide, leading to the rearrangement of smaller lipids. These findings help explain the experimentally observed or proposed differences in the insertion depth, binding strength, and structural transition of E and K peptides, and support the snorkeling effect. PMID:26926570

  10. All-atom simulations and free-energy calculations of coiled-coil peptides with lipid bilayers: binding strength, structural transition, and effect on lipid dynamics.

    PubMed

    Woo, Sun Young; Lee, Hwankyu

    2016-03-01

    Peptides E and K, which are synthetic coiled-coil peptides for membrane fusion, were simulated with lipid bilayers composed of lipids and cholesterols at different ratios using all-atom models. We first calculated free energies of binding from umbrella sampling simulations, showing that both E and K peptides tend to adsorb onto the bilayer surface, which occurs more strongly in the bilayer composed of smaller lipid headgroups. Then, unrestrained simulations show that K peptides more deeply insert into the bilayer with partially retaining the helical structure, while E peptides less insert and predominantly become random coils, indicating the structural transition from helices to random coils, in quantitative agreement with experiments. This is because K peptides electrostatically interact with lipid phosphates, as well as because hydrocarbons of lysines of K peptide are longer than those of glutamic acids of E peptide and thus form stronger hydrophobic interactions with lipid tails. This deeper insertion of K peptide increases the bilayer dynamics and a vacancy below the peptide, leading to the rearrangement of smaller lipids. These findings help explain the experimentally observed or proposed differences in the insertion depth, binding strength, and structural transition of E and K peptides, and support the snorkeling effect.

  11. All-atom simulations and free-energy calculations of coiled-coil peptides with lipid bilayers: binding strength, structural transition, and effect on lipid dynamics

    NASA Astrophysics Data System (ADS)

    Woo, Sun Young; Lee, Hwankyu

    2016-03-01

    Peptides E and K, which are synthetic coiled-coil peptides for membrane fusion, were simulated with lipid bilayers composed of lipids and cholesterols at different ratios using all-atom models. We first calculated free energies of binding from umbrella sampling simulations, showing that both E and K peptides tend to adsorb onto the bilayer surface, which occurs more strongly in the bilayer composed of smaller lipid headgroups. Then, unrestrained simulations show that K peptides more deeply insert into the bilayer with partially retaining the helical structure, while E peptides less insert and predominantly become random coils, indicating the structural transition from helices to random coils, in quantitative agreement with experiments. This is because K peptides electrostatically interact with lipid phosphates, as well as because hydrocarbons of lysines of K peptide are longer than those of glutamic acids of E peptide and thus form stronger hydrophobic interactions with lipid tails. This deeper insertion of K peptide increases the bilayer dynamics and a vacancy below the peptide, leading to the rearrangement of smaller lipids. These findings help explain the experimentally observed or proposed differences in the insertion depth, binding strength, and structural transition of E and K peptides, and support the snorkeling effect.

  12. Structural features of small benzene clusters (C6H6)n (n ≤ 30) as investigated with the all-atom OPLS potential.

    PubMed

    Takeuchi, Hiroshi

    2012-10-18

    The structures of the simplest aromatic clusters, benzene clusters (C(6)H(6))(n), are not well elucidated. In the present study, benzene clusters (C(6)H(6))(n) (n ≤ 30) were investigated with the all-atom optimized parameters for liquid simulation (OPLS) potential. The global minima and low-lying minima of the benzene clusters were searched with the heuristic method combined with geometrical perturbations. The structural features and growth sequence of the clusters were examined by carrying out local structure analyses and structural similarity evaluation with rotational constants. Because of the anisotropic interaction between the benzene molecules, the local structures consisting of 13 molecules are considerably deviated from regular icosahedron, and the geometries of some of the clusters are inconsistent with the shapes constructed by the interior molecules. The distribution of the angle between the lines normal to two neighboring benzene rings is anisotropic in the clusters, whereas that in the liquid benzene is nearly isotropic. The geometries and energies of the low-lying configurations and the saddle points between them suggest that most of the configurations previously detected in supersonic expansions take different orientations for one to four neighboring molecules.

  13. Effects of Water Models on Binding Affinity: Evidence from All-Atom Simulation of Binding of Tamiflu to A/H5N1 Neuraminidase

    PubMed Central

    Nguyen, Trang Truc; Viet, Man Hoang

    2014-01-01

    The influence of water models SPC, SPC/E, TIP3P, and TIP4P on ligand binding affinity is examined by calculating the binding free energy ΔGbind of oseltamivir carboxylate (Tamiflu) to the wild type of glycoprotein neuraminidase from the pandemic A/H5N1 virus. ΔGbind is estimated by the Molecular Mechanic-Poisson Boltzmann Surface Area method and all-atom simulations with different combinations of these aqueous models and four force fields AMBER99SB, CHARMM27, GROMOS96 43a1, and OPLS-AA/L. It is shown that there is no correlation between the binding free energy and the water density in the binding pocket in CHARMM. However, for three remaining force fields ΔGbind decays with increase of water density. SPC/E provides the lowest binding free energy for any force field, while the water effect is the most pronounced in CHARMM. In agreement with the popular GROMACS recommendation, the binding score obtained by combinations of AMBER-TIP3P, OPLS-TIP4P, and GROMOS-SPC is the most relevant to the experiments. For wild-type neuraminidase we have found that SPC is more suitable for CHARMM than TIP3P recommended by GROMACS for studying ligand binding. However, our study for three of its mutants reveals that TIP3P is presumably the best choice for CHARMM. PMID:24672329

  14. Effects of water models on binding affinity: evidence from all-atom simulation of binding of tamiflu to A/H5N1 neuraminidase.

    PubMed

    Nguyen, Trang Truc; Viet, Man Hoang; Li, Mai Suan

    2014-01-01

    The influence of water models SPC, SPC/E, TIP3P, and TIP4P on ligand binding affinity is examined by calculating the binding free energy ΔG(bind) of oseltamivir carboxylate (Tamiflu) to the wild type of glycoprotein neuraminidase from the pandemic A/H5N1 virus. ΔG(bind) is estimated by the Molecular Mechanic-Poisson Boltzmann Surface Area method and all-atom simulations with different combinations of these aqueous models and four force fields AMBER99SB, CHARMM27, GROMOS96 43a1, and OPLS-AA/L. It is shown that there is no correlation between the binding free energy and the water density in the binding pocket in CHARMM. However, for three remaining force fields ΔG(bind) decays with increase of water density. SPC/E provides the lowest binding free energy for any force field, while the water effect is the most pronounced in CHARMM. In agreement with the popular GROMACS recommendation, the binding score obtained by combinations of AMBER-TIP3P, OPLS-TIP4P, and GROMOS-SPC is the most relevant to the experiments. For wild-type neuraminidase we have found that SPC is more suitable for CHARMM than TIP3P recommended by GROMACS for studying ligand binding. However, our study for three of its mutants reveals that TIP3P is presumably the best choice for CHARMM.

  15. An all-atom model of the pore-like structure of hexameric VP40 from Ebola: structural insights into the monomer-hexamer transition.

    PubMed

    Nguyen, Tam Luong; Schoehn, Guy; Weissenhorn, Winfried; Hermone, Ann R; Burnett, James C; Panchal, Rekha G; McGrath, Connor; Zaharevitz, Dan W; Aman, M Javad; Gussio, Rick; Bavari, Sina

    2005-07-01

    The matrix protein VP40 is an indispensable component of viral assembly and budding by the Ebola virus. VP40 is a monomer in solution, but can fold into hexameric and octameric states, two oligomeric conformations that play central roles in the Ebola viral life cycle. While the X-ray structures of monomeric and octameric VP40 have been determined, the structure of hexameric VP40 has only been solved by three-dimensional electron microscopy (EM) to a resolution of approximately 30 A. In this paper, we present the refinement of the EM reconstruction of truncated hexameric VP40 to approximately 20 A and the construction of an all-atom model (residues 44-212) using the EM model at approximately 20 A and the X-ray structure of monomeric VP40 as templates. The hexamer model suggests that the monomer-hexamer transition involves a conformational change in the N-terminal domain that is not evident during octamerization and therefore, may provide the basis for elucidating the biological function of VP40.

  16. Development of a new meta-score for protein structure prediction from seven all-atom distance dependent potentials using support vector regression.

    PubMed

    Shirota, Matsuyuki; Ishida, Takashi; Kinoshita, Kengo

    2009-10-01

    An accurate scoring function is required for protein structure prediction. The scoring function should distinguish the native structure among model structures (decoys) and it also should have correlation with the quality of the decoys. However, we had observed the trade-off between the two requirements for seven all-atom distance dependent potentials in the previous study, where the native structure could be discriminated by examining the fine atomic details, whereas the correlation could be improved by examining coarse-grained interactions, To overcome this problem, in this study, we tried to make an improved scoring function by combining the seven potentials. First, the seven potentials were normalized by the expected energy values of the native and reference states of the target protein. Second, the relationship between the seven normalized energies and the quality (GDT_TS) of the structure were learned using support vector regression with the decoy sets of CASP6 as the training set. Then the meta-score was obtained as the predicted GDT_TS and it was tested with the decoys of the CASP7 experiment. The meta-score showed improvement in correlations with the GDT_TS and in the Z-score of the native structure. It also showed comparable performances in the GDT and enrichment criteria, with the best component potentials. The meta-score could be also used as the absolute quality of the structures. Our study suggests the benefit of combining several different scoring functions for model evaluation.

  17. Uncovering the microscopic mechanism of strand exchange during RecA mediated homologous recombination using all-atom molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Shankla, Manish; Yoo, Jejoong; Aksimentiev, Aleksei

    2012-02-01

    Homologous recombination (HR) is a key step during the repair process of double-stranded DNA (dsDNA) breakage. RecA is a protein that mediates HR in bacteria. RecA monomers polymerize on a single-stranded DNA (ssDNA) separated from the broken dsDNA to form a helical filament, thus allowing strand exchange to occur. Recent crystal structures depict each RecA monomer in contact with three contiguous nucleotides called DNA triplets. Surprisingly, the conformation of each triplet is similar to that of a triplet in B-form DNA. However, in the filament the neighboring triplets are separated by loops of the RecA proteins. Single molecule experiments demonstrated that strand exchange propagation occurs in 3 base-pair increments. However, the temporal resolution of the experiments was insufficient to determine the exact molecular mechanism of the triplet propagation. Using all-atom molecular dynamics simulations, we investigated the effect of both the RecA protein and the conformation of the bound ssDNA fragment on the stability of the duplex DNA intermediate formed during the strand-exchange process. Specifically, we report simulations of force-induced unzipping of duplex DNA in the presence and absence of the RecA filament that explored the effect of the triplet ladder conformation.

  18. Solvents in novolak synthesis

    NASA Astrophysics Data System (ADS)

    Sobodacha, Chet J.; Lynch, Thomas J.; Durham, Dana L.; Paradis, Valerie R.

    1993-09-01

    Novolac resins may be prepared with or without a solvent present. We have found that solvent power greatly affects the properties of the finished resin and thus gives the resist chemist another variable with which to `fine-tune' resist properties. Using designed experiments, we investigated the effect of solvent power, as measured by Hansen's Solubility Parameters, of a number of solvents and solvent mixtures on the final properties of the novolac resin. We found that the relative molecular weight (RMW) and dissolution rate of a novolac resin can be varied by selection of a solvent or solvent mixture with the appropriate polarity and hydrogen- bonding characteristics. The solvent polarity and hydrogen-bonding characteristics may affect the stability of the cresol/formaldehyde transition state, thus causing the observed changes in RMW and dissolution rate.

  19. Solvent Recycling for Shipyards

    DTIC Science & Technology

    1993-05-01

    alternatives to solvent cleaning. Typical equipment types that can be effectively cleaned with recycled solvents include spray guns paint hoses pumps...in place of solvent-based coatings; or equipment changes, such as the use of airless or HVLP systems to reduce paint consumption and overspray...Using mechanical cleaning methods instead of solvent cleaning Change from conventional painting to solventless processes such as thermal spray or powder

  20. NEPTUNIUM SOLVENT EXTRACTION PROCESS

    DOEpatents

    Dawson, L.R.; Fields, P.R.

    1959-10-01

    The separation of neptunium from an aqueous solution by solvent extraction and the extraction of neptunium from the solvent solution are described. Neptunium is separated from an aqueous solution containing tetravalent or hexavalent neptunium nitrate, nitric acid, and a nitrate salting out agent, such as sodium nitrate, by contacting the solution with an organic solvent such as diethyl ether. Subsequently, the neptunium nitrate is extracted from the organic solvent extract phase with water.

  1. Membrane protein simulations with a united-atom lipid and all-atom protein model: lipid protein interactions, side chain transfer free energies and model proteins

    NASA Astrophysics Data System (ADS)

    Tieleman, D. Peter; MacCallum, Justin L.; Ash, Walter L.; Kandt, Christian; Xu, Zhitao; Monticelli, Luca

    2006-07-01

    We have reparameterized the dihedral parameters in a commonly used united-atom lipid force field so that they can be used with the all-atom OPLS force field for proteins implemented in the molecular dynamics simulation software GROMACS. Simulations with this new combination give stable trajectories and sensible behaviour of both lipids and protein. We have calculated the free energy of transfer of amino acid side chains between water and 'lipid-cyclohexane', made of lipid force field methylene groups, as a hydrophobic mimic of the membrane interior, for both the OPLS-AA and a modified OPLS-AA force field which gives better hydration free energies under simulation conditions close to those preferred for the lipid force field. The average error is 4.3 kJ mol-1 for water-'lipid-cyclohexane' compared to 3.2 kJ mol-1 for OPLS-AA cyclohexane and 2.4 kJ mol-1 for the modified OPLS-AA water-'lipid-cyclohexane'. We have also investigated the effect of different methods to combine parameters between the united-atom lipid force field and the united-atom protein force field ffgmx. In a widely used combination, the strength of interactions between hydrocarbon lipid tails and proteins is significantly overestimated, causing a decrease in the area per lipid and an increase in lipid ordering. Using straight combination rules improves the results. Combined, we suggest that using OPLS-AA together with the united-atom lipid force field implemented in GROMACS is a reasonable approach to membrane protein simulations. We also suggest that using partial volume information and free energies of transfer may help to improve the parameterization of lipid-protein interactions and point out the need for accurate experimental data to validate and improve force field descriptions of such interactions.

  2. All-atom structural models of insulin binding to the insulin receptor in the presence of a tandem hormone-binding element.

    PubMed

    Vashisth, Harish; Abrams, Cameron F

    2013-06-01

    Insulin regulates blood glucose levels in higher organisms by binding to and activating insulin receptor (IR), a constitutively homodimeric glycoprotein of the receptor tyrosine kinase (RTK) superfamily. Therapeutic efforts in treating diabetes have been significantly impeded by the absence of structural information on the activated form of the insulin/IR complex. Mutagenesis and photo-crosslinking experiments and structural information on insulin and apo-IR strongly suggest that the dual-chain insulin molecule, unlike the related single-chain insulin-like growth factors, binds to IR in a very different conformation than what is displayed in storage forms of the hormone. In particular, hydrophobic residues buried in the core of the folded insulin molecule engage the receptor. There is also the possibility of plasticity in the receptor structure based on these data, which may in part be due to rearrangement of the so-called CT-peptide, a tandem hormone-binding element of IR. These possibilities provide opportunity for large-scale molecular modeling to contribute to our understanding of this system. Using various atomistic simulation approaches, we have constructed all-atom structural models of hormone/receptor complexes in the presence of CT in its crystallographic position and a thermodynamically favorable displaced position. In the "displaced-CT" complex, many more insulin-receptor contacts suggested by experiments are satisfied, and our simulations also suggest that R-insulin potentially represents the receptor-bound form of hormone. The results presented in this work have further implications for the design of receptor-specific agonists/antagonists.

  3. Membrane protein simulations with a united-atom lipid and all-atom protein model: lipid-protein interactions, side chain transfer free energies and model proteins.

    PubMed

    Tieleman, D Peter; Maccallum, Justin L; Ash, Walter L; Kandt, Christian; Xu, Zhitao; Monticelli, Luca

    2006-07-19

    We have reparameterized the dihedral parameters in a commonly used united-atom lipid force field so that they can be used with the all-atom OPLS force field for proteins implemented in the molecular dynamics simulation software GROMACS. Simulations with this new combination give stable trajectories and sensible behaviour of both lipids and protein. We have calculated the free energy of transfer of amino acid side chains between water and 'lipid-cyclohexane', made of lipid force field methylene groups, as a hydrophobic mimic of the membrane interior, for both the OPLS-AA and a modified OPLS-AA force field which gives better hydration free energies under simulation conditions close to those preferred for the lipid force field. The average error is 4.3 kJ mol(-1) for water-'lipid-cyclohexane' compared to 3.2 kJ mol(-1) for OPLS-AA cyclohexane and 2.4 kJ mol(-1) for the modified OPLS-AA water-'lipid-cyclohexane'. We have also investigated the effect of different methods to combine parameters between the united-atom lipid force field and the united-atom protein force field ffgmx. In a widely used combination, the strength of interactions between hydrocarbon lipid tails and proteins is significantly overestimated, causing a decrease in the area per lipid and an increase in lipid ordering. Using straight combination rules improves the results. Combined, we suggest that using OPLS-AA together with the united-atom lipid force field implemented in GROMACS is a reasonable approach to membrane protein simulations. We also suggest that using partial volume information and free energies of transfer may help to improve the parameterization of lipid-protein interactions and point out the need for accurate experimental data to validate and improve force field descriptions of such interactions.

  4. Solvents and sustainable chemistry

    PubMed Central

    Welton, Tom

    2015-01-01

    Solvents are widely recognized to be of great environmental concern. The reduction of their use is one of the most important aims of green chemistry. In addition to this, the appropriate selection of solvent for a process can greatly improve the sustainability of a chemical production process. There has also been extensive research into the application of so-called green solvents, such as ionic liquids and supercritical fluids. However, most examples of solvent technologies that give improved sustainability come from the application of well-established solvents. It is also apparent that the successful implementation of environmentally sustainable processes must be accompanied by improvements in commercial performance. PMID:26730217

  5. Solvent recycle/recovery

    SciTech Connect

    Paffhausen, M.W.; Smith, D.L.; Ugaki, S.N.

    1990-09-01

    This report describes Phase I of the Solvent Recycle/Recovery Task of the DOE Chlorinated Solvent Substitution Program for the US Air Force by the Idaho National Engineering Laboratory, EG G Idaho, Inc., through the US Department of Energy, Idaho Operations Office. The purpose of the task is to identify and test recovery and recycling technologies for proposed substitution solvents identified by the Biodegradable Solvent Substitution Program and the Alternative Solvents/Technologies for Paint Stripping Program with the overall objective of minimizing hazardous wastes. A literature search to identify recycle/recovery technologies and initial distillation studies has been conducted. 4 refs.

  6. Implicit and Explicit Learning of Languages.

    ERIC Educational Resources Information Center

    McDermott, James E.

    1999-01-01

    Discusses theoretical and practical issues connected with implicit and explicit learning of languages. Explicit learning is knowledge expressed in the form of rules or definitions; implicit knowledge can be inferred to exist because of observed performance but cannot be clearly described. Hypothesizes why explicit learning can lead to implicit…

  7. Using Implicit Solvent in Ab Initio Electrochemical Modeling: Investigating Li⁺/Li Electrochemistry at a Li/Solvent Interface.

    PubMed

    Lespes, Nicolas; Filhol, Jean-Sébastien

    2015-07-14

    This paper focuses on the use of implicit solvent in electrochemical density functional theory (DFT) calculations. We investigate both the necessity and limits of an implicit solvent polarizable continuum model (PCM). In order to recover the proper electrochemical behavior of the surface and, in particular, a proper potential scale, the solvent model is determined to be mandatory: in the limit of a high dielectric constant, the surface capacitance becomes independent of the interslab space used in the model and, therefore, the electrochemical properties become intrinsic of the interface structure. We show that the computed surface capacitance is not only dependent on the implicit solvent dielectric constant, but also on the solvent cavity parameter that should be precisely tuned. This model is then applied to the Li/electrolyte interface in order to check its ability to compute thermodynamic equilibrium properties. The use of a purely implicit solvent approach allows the recovery of a more reasonable equilibrium potential for the Li(+)/Li redox pair, compared to vacuum approaches, but a potential that it is still off by 1.5 V. Then, the inclusion of explicit solvent molecules improves the description of the solvent-Li(+) chemical bond in the first solvation shell and allows recovery of the experimental value within 100 mV. Finally, we show that the redox active center involves the first solvation shell of Li(+), suggesting a particular pathway for the observed solvent dissociation in Li-ion batteries.

  8. Unified description of solvent effects in the helix-coil transition

    NASA Astrophysics Data System (ADS)

    Badasyan, Artem; Tonoyan, Shushanik A.; Giacometti, Achille; Podgornik, Rudolf; Parsegian, V. Adrian; Mamasakhlisov, Yevgeni Sh.; Morozov, Vladimir F.

    2014-02-01

    We analyze the problem of the helix-coil transition in explicit solvents analytically by using spin-based models incorporating two different mechanisms of solvent action: explicit solvent action through the formation of solvent-polymer hydrogen bonds that can compete with the intrinsic intra-polymer hydrogen bonded configurations (competing interactions) and implicit solvent action, where the solvent-polymer interactions tune biopolymer configurations by changing the activity of the solvent (non-competing interactions). The overall spin Hamiltonian is comprised of three terms: the background in vacuo Hamiltonian of the "Generalized Model of Polypeptide Chain" type and two additive terms that account for the two above mechanisms of solvent action. We show that on this level the solvent degrees of freedom can be explicitly and exactly traced over, the ensuing effective partition function combining all the solvent effects in a unified framework. In this way we are able to address helix-coil transitions for polypeptides, proteins, and DNA, with different buffers and different external constraints. Our spin-based effective Hamiltonian is applicable for treatment of such diverse phenomena as cold denaturation, effects of osmotic pressure on the cold and warm denaturation, complicated temperature dependence of the hydrophobic effect as well as providing a conceptual base for understanding the behavior of intrinsically disordered proteins and their analogues.

  9. SOLVENT EXTRACTION OF NEPTUNIUM

    DOEpatents

    Butler, J.P.

    1958-08-12

    A process is described for the recovery of neptuniunn from dissolver solutions by solvent extraction. The neptunium containing solution should be about 5N, in nitric acid.and about 0.1 M in ferrous ion. The organic extracting agent is tributyl phosphate, and the neptuniunn is recovered from the organic solvent phase by washing with water.

  10. Solvent-free synthesis

    EPA Science Inventory

    This chapter gives a brief introduction about solvent-free reactions whose importance can be gauged by the increasing number of publications every year during the last decade. The mechanistic aspects of the reactions under solvent-free conditions have been highlighted. Our observ...

  11. Organic solvent simulations under non-periodic boundary conditions: A library of effective potentials for the GLOB model

    NASA Astrophysics Data System (ADS)

    Mancini, Giordano; Brancato, Giuseppe; Chandramouli, Balasubramanian; Barone, Vincenzo

    2015-04-01

    We extend the library of solvents that can be treated using the GLOB (general liquid optimized boundary) method, that allows to perform MD simulations under non-periodic boundary conditions (NPBC) optimizing effective potentials between explicit molecules and the boundary for four organic solvents: CHCl3, CCl4, CH3OH and CH3CN. We show that GLOB allows reducing the number of explicit solvent shells to be included, while yielding results comparable with PBC and significant advantages over simulations without explicit boundaries. Finally, we provide polynomial fittings for all available GLOB effective potentials (including SPC water) to simplify their implementation in NPBC MD simulations.

  12. Alternative Green Solvents Project

    NASA Technical Reports Server (NTRS)

    Maloney, Phillip R.

    2012-01-01

    Necessary for safe and proper functioning of equipment. Mainly halogenated solvents. Tetrachloride, Trichloroethylene (TCE), CFC-113. No longer used due to regulatory/safety concerns. Precision Cleaning at KSC: Small % of total parts. Used for liquid oxygen (LOX) systems. Dual solvent process. Vertrel MCA (decafluoropentane (DFP) and trons-dichloroethylene) HFE-7100. DFP has long term environmental concerns. Project Goals: a) Identify potential replacements. b) 22 wet chemical processes. c) 3 alternative processes. d) Develop test procedures. e) Contamination and cleaning. f) Analysis. g) Use results to recommend alternative processes. Conclusions: a) No alternative matched Vertrel in this study. b) No clear second place solvent. c) Hydrocarbons- easy; Fluorinated greases- difficult. d) Fluorinated component may be needed in replacement solvent. e) Process may need to make up for shortcoming of the solvent. f) Plasma and SCC02 warrant further testing.

  13. SOLVENT EXTRACTION PROCESS

    DOEpatents

    Jonke, A.A.

    1957-10-01

    In improved solvent extraction process is described for the extraction of metal values from highly dilute aqueous solutions. The process comprises contacting an aqueous solution with an organic substantially water-immiscible solvent, whereby metal values are taken up by a solvent extract phase; scrubbing the solvent extract phase with an aqueous scrubbing solution; separating an aqueous solution from the scrubbed solvent extract phase; and contacting the scrubbed solvent phase with an aqueous medium whereby the extracted metal values are removed from the solvent phase and taken up by said medium to form a strip solution containing said metal values, the aqueous scrubbing solution being a mixture of strip solution and an aqueous solution which contains mineral acids anions and is free of the metal values. The process is particularly effective for purifying uranium, where one starts with impure aqueous uranyl nitrate, extracts with tributyl phosphate dissolved in carbon tetrachloride, scrubs with aqueous nitric acid and employs water to strip the uranium from the scrubbed organic phase.

  14. A comparative VCD study of methyl mandelate in methanol, dimethyl sulfoxide, and chloroform: explicit and implicit solvation models.

    PubMed

    Poopari, Mohammad Reza; Dezhahang, Zahra; Xu, Yunjie

    2013-02-07

    Vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra of methyl mandelate, a prototype chiral molecule, in a series of organic solvents, namely methanol (MeOH-d(4)), dimethyl sulfoxide (DMSO-d(6)), and chloroform (CDCl(3)), have been measured in the finger print region from 1800 to 1150 cm(-1). Implicit solvation models in the form of polarizable continuum model and explicit solvation models have been employed independently and simultaneously. The goal is to evaluate their efficiencies in dealing with solvent effects in each solution and to establish a general strategy to adequately account for effects of solvents. Molecular dynamics (MD) simulation and radial distribution function analysis have been performed to aid the construction of the explicit solvation models. Initial geometry searches have been carried out at the B3LYP/6-31G(d) level for the methyl mandelate monomer and its explicit 1 : 1 and 1 : 2 solute-solvent hydrogen-bonded complexes. B3LYP/cc-pVTZ has been used for all the final geometry optimizations, the vibrational frequency, VA and VCD intensity, and optical rotation dispersion (ORD) calculations. The results show that inclusion of solvent explicitly and implicitly at the same time has significant impacts on the appearance of the VA and VCD spectra, and is crucial for reliable spectral assignments when solvents are capable of hydrogen-bonding interactions with solutes. When no strong solvent-solute hydrogen-bonding interactions in the case of chloroform are expected, the gas phase monomer model is adequate for spectral interpretation, while inclusion of implicit solvation improves the frequency agreement with experiment. ORD spectra of methyl mandelate in the aforementioned solvents at different concentrations under 5 excitation wavelengths have also been measured. The comparison between the calculated and the experimental ORD spectra supports the conclusions drawn from the VA and VCD investigations.

  15. Solvent alternatives guide

    SciTech Connect

    Elion, J.M.; Monroe, K.R.; Hill, E.A.

    1996-06-01

    It is no longer legal to manufacture or import chlorofluorocarbon 113 or methyl chloroform solvents, and companies that currently clean their parts with either material are now required to implement environmentally safe substitutes. To help find alternative methods, Research Triangle Institute`s Surface Cleaning Technology Program has designed a Solvent Alternatives Guide (SAGE), an online tool that enables access to practical information and recommendations for acceptable solvents. Developed in partnership with the US Environmental Protection Agency, SAGE is available free of charge on the Internet`s World Wide Web.

  16. Development of Implicit and Explicit Category Learning

    ERIC Educational Resources Information Center

    Huang-Pollock, Cynthia L.; Maddox, W. Todd; Karalunas, Sarah L.

    2011-01-01

    We present two studies that examined developmental differences in the implicit and explicit acquisition of category knowledge. College-attending adults consistently outperformed school-age children on two separate information-integration paradigms due to children's more frequent use of an explicit rule-based strategy. Accuracy rates were also…

  17. Implicit and Explicit Exercise and Sedentary Identity

    ERIC Educational Resources Information Center

    Berry, Tanya R.; Strachan, Shaelyn M.

    2012-01-01

    We examined the relationship between implicit and explicit "exerciser" and "sedentary" self-identity when activated by stereotypes. Undergraduate participants (N = 141) wrote essays about university students who either liked to exercise or engage in sedentary activities. This was followed by an implicit identity task and an explicit measure of…

  18. Thinking Styles in Implicit and Explicit Learning

    ERIC Educational Resources Information Center

    Xie, Qiuzhi; Gao, Xiangping; King, Ronnel B.

    2013-01-01

    This study investigated whether individual differences in thinking styles influence explicit and implicit learning. Eighty-seven university students in China participated in this study. Results indicated that performance in the explicit learning condition was positively associated with Type I thinking styles (i.e. legislative and liberal styles)…

  19. Implicit and Explicit Instruction of Spelling Rules

    ERIC Educational Resources Information Center

    Kemper, M. J.; Verhoeven, L.; Bosman, A. M. T.

    2012-01-01

    The study aimed to compare the differential effectiveness of explicit and implicit instruction of two Dutch spelling rules. Students with and without spelling disabilities were instructed a spelling rule either implicitly or explicitly in two experiments. Effects were tested in a pretest-intervention-posttest control group design. Experiment 1…

  20. CHLORINATED SOLVENT PLUME CONTROL

    EPA Science Inventory

    This lecture will cover recent success in controlling and assessing the treatment of shallow ground water plumes of chlorinated solvents, other halogenated organic compounds, and methyl tert-butyl ether (MTBE).

  1. Molar Absorptivity Measurements in Absorbing Solvents: Impact on Solvent Absorptivity Values.

    PubMed

    Bohman, Ariel; Arnold, Mark A

    2016-10-18

    Molar absorptivity is a fundamental molecular property that quantifies absorption strength as a function of wavelength. Absolute measurements of molar absorptivity demand accounting for all mechanisms of light attenuation, including reflective losses at interfaces associated with the sample. Ideally, such measurements are performed in nonabsorbing solvents and reflective losses can be determined in a straightforward manner from Fresnel equations or effectively accounted for by path length difference methods. At near-infrared wavelengths, however, many solvents, including water, are absorbing which complicates the quantification of reflective losses. Here, generalized equations are developed for calculating absolute molar absorptivities of neat liquids wherein the dependency of reflective loss on absorption properties of the liquid are considered explicitly. The resulting equations are used to characterize sensitivity of absolute molar absorptivity measurements for solvents to the absorption strength of the solvent as well as the path length of the measurement. Methods are derived from these equations to properly account for reflective losses in general and the effectiveness of these methods is demonstrated for absolute molar absorptivity measurements for water over the combination region (5000-4000 cm(-1)) of the near-infrared spectrum. Results indicate that ignoring solvent absorption effects can incorporate wide ranging systematic errors depending upon experimental conditions. As an example, systematic errors range from 0 to 10% for common conditions used in the measurement of absolute molar absorptivity of water over the combination region of the near-infrared spectrum.

  2. Continuous countercurrent membrane column for the separation of solute/solvent and solvent/solvent systems

    DOEpatents

    Nerad, Bruce A.; Krantz, William B.

    1988-01-01

    A reverse osmosis membrane process or hybrid membrane - complementary separator process for producing enriched product or waste streams from concentrated and dilute feed streams for both solvent/solvent and solute/solvent systems is described.

  3. SOLVENT EXTRACTION OF RUTHENIUM

    DOEpatents

    Hyman, H.H.; Leader, G.R.

    1959-07-14

    The separation of rathenium from aqueous solutions by solvent extraction is described. According to the invention, a nitrite selected from the group consisting of alkali nitrite and alkaline earth nitrite in an equimolecular quantity with regard to the quantity of rathenium present is added to an aqueous solution containing ruthenium tetrantrate to form a ruthenium complex. Adding an organic solvent such as ethyl ether to the resulting mixture selectively extracts the rathenium complex.

  4. Supercritical solvent coal extraction

    NASA Technical Reports Server (NTRS)

    Compton, L. E. (Inventor)

    1984-01-01

    Yields of soluble organic extract are increased up to about 50% by the supercritical extraction of particulate coal at a temperature below the polymerization temperature for coal extract fragments (450 C.) and a pressure from 500 psig to 5,000 psig by the conjoint use of a solvent mixture containing a low volatility, high critical temperature coal dissolution catalyst such as phenanthrene and a high volatility, low critical temperature solvent such as toluene.

  5. Solvent effects on chemical processes. I: Solubility of aromatic and heterocyclic compounds in binary aqueous-organic solvents.

    PubMed

    Khossravi, D; Connors, K A

    1992-04-01

    The standard free energy change (delta G0) for equilibrium dissolution in binary solvent mixtures is written as a sum of effects arising from solvent-solvent interactions (the general medium effect), solvent-solute interactions (the solvation effect), and solute-solute interactions (the intersolute effect). The general medium effect is given by gA gamma, where g is a curvature correction factor to the surface tension (gamma) and A is the molecular cavity surface area. A new feature is the definition of gamma to be that value appropriate to the equilibrium mean solvation shell composition. The solvation effect is modeled by stoichiometric stepwise competitive equilibria between the two solvent components for the solute. The intersolute effect includes the crystal energy and solution phase interactions. In this work, water was solvent component 1, and various miscible organic cosolvents served as solvent component 2. Relating all data to the fully aqueous solution gives an explicit expression for delta M delta G0, the solvent effect on the free energy change, as a function of the mole fractions x1 and x2. This function is a binding isotherm. Nonlinear regression leads (for a two-step solvation scheme) to estimates of the solvation exchange constants K1 and K2 and the parameter gA. This relationship was applied to 44 systems comprising combinations of 31 solutes and eight organic cosolvents. Curve fits were good to excellent, and most of the parameter estimates had physically reasonable magnitudes.

  6. Cleaning without chlorinated solvents

    SciTech Connect

    Thompson, L.M.; Simandl, R.F.

    1994-12-31

    Because of health and environmental concerns, many regulations have been passed in recent years regarding the use of chlorinated solvents. The Oak Ridge Y-12 Plant has had an active program to find alternatives for these solvents used in cleaning applications for the past 7 years. During this time frame, the quantity of solvents purchased has been reduced by 92%. The program has been a twofold effort. Vapor degreasers used in batch cleaning-operations have been replaced by ultrasonic cleaning with aqueous detergent, and other organic solvents have been identified for use in hand-wiping or specialty operations. In order to qualify these alternatives for use, experimentation was conducted on cleaning ability as well as effects on subsequent operations such as welding, painting and bonding. Cleaning ability was determined using techniques such as X-ray photoelectron spectroscopy (XPS) and Fourier Transform Infrared Spectroscopy (FTIR) which are capable of examining monolayer levels of contamination on a surface. Solvents have been identified for removal of rust preventative oils, lapping oils, machining coolants, lubricants, greases, and mold releases. Solvents have also been evaluated for cleaning urethane foam spray guns, swelling of urethanes and swelling of epoxies.

  7. Cleaning without chlorinated solvents

    NASA Technical Reports Server (NTRS)

    Thompson, L. M.; Simandl, R. F.

    1995-01-01

    Because of health and environmental concerns, many regulations have been passed in recent years regarding the use of chlorinated solvents. The Oak Ridge Y-12 Plant has had an active program to find alternatives for these solvents used in cleaning applications for the past 7 years. During this time frame, the quantity of solvents purchased has been reduced by 92 percent. The program has been a twofold effort. Vapor degreasers used in batch cleaning operations have been replaced by ultrasonic cleaning with aqueous detergent, and other organic solvents have been identified for use in hand-wiping or specialty operations. In order to qualify these alternatives for use, experimentation was conducted on cleaning ability as well as effects on subsequent operations such as welding, painting, and bonding. Cleaning ability was determined using techniques such as x-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) which are capable of examining monolayer levels of contamination on a surface. Solvents have been identified for removal of rust preventative oils, lapping oils, machining coolants, lubricants, greases, and mold releases. Solvents have also been evaluated for cleaning urethane foam spray guns, swelling of urethanes, and swelling of epoxies.

  8. Generation of Well-Relaxed All-Atom Models of Large Molecular Weight Polymer Melts: A Hybrid Particle-Continuum Approach Based on Particle-Field Molecular Dynamics Simulations.

    PubMed

    De Nicola, Antonio; Kawakatsu, Toshihiro; Milano, Giuseppe

    2014-12-09

    A procedure based on Molecular Dynamics (MD) simulations employing soft potentials derived from self-consistent field (SCF) theory (named MD-SCF) able to generate well-relaxed all-atom structures of polymer melts is proposed. All-atom structures having structural correlations indistinguishable from ones obtained by long MD relaxations have been obtained for poly(methyl methacrylate) (PMMA) and poly(ethylene oxide) (PEO) melts. The proposed procedure leads to computational costs mainly related on system size rather than to the chain length. Several advantages of the proposed procedure over current coarse-graining/reverse mapping strategies are apparent. No parametrization is needed to generate relaxed structures of different polymers at different scales or resolutions. There is no need for special algorithms or back-mapping schemes to change the resolution of the models. This characteristic makes the procedure general and its extension to other polymer architectures straightforward. A similar procedure can be easily extended to the generation of all-atom structures of block copolymer melts and polymer nanocomposites.

  9. Implicit sequence learning with competing explicit cues.

    PubMed

    Jiménez, L; Méndez, C

    2001-05-01

    Previous research has shown that the expression of implicit sequence learning is eliminated in a choice reaction time task when an explicit cue allows participants to accurately predict the next stimulus (Cleeremans, 1997), but that two contingencies predicting the same outcome can be learned and expressed simultaneously when both of them remain implicit (Jiménez & Méndez, 1999). Two experiments tested the hypothesis that it is the deliberate use of explicit knowledge that produces the inhibitory effects over the expression of implicit sequence learning. However, the results of these experiments do not support this hypothesis, rather showing that implicit learning is acquired and expressed regardless of the influence of explicit knowledge. These results are interpreted as reinforcing the thesis about the automatic nature of both the acquisition and the expression of implicit sequence learning. The contradictory results reported by Cleeremans are attributed to a floor effect derived from the use of a special type of explicit cue.

  10. A linear scaling study of solvent-solute interaction energy of drug molecules in aqua solution.

    PubMed

    Bondesson, Laban; Rudberg, Elias; Luo, Yi; Sałek, Paweł

    2007-08-30

    Solvent-solute interaction energies for three well-known drug molecules in water solution are computed at the Hartree-Fock and B3LYP density functional theory levels using a linear scaling technique, which allows one to explicitly include in the model water molecules up to 14 A away from the solute molecule. The dependence of calculated interaction energies on the amount of included solvent has been examined. It is found that it is necessary to account for water molecules within an 8 A radius around the drug molecule to reach the saturated solvent interaction level. Effects of electron correlation and basis set on solvent-solute interaction energies are discussed.

  11. Parallel Generalized Born Implicit Solvent Calculations with NAMD.

    PubMed

    Tanner, David E; Chan, Kwok-Yan; Phillips, James C; Schulten, Klaus

    2011-11-08

    Accurate electrostatic descriptions of aqueous solvent are critical for simulation studies of bio-molecules, but the computational cost of explicit treatment of solvent is very high. A computationally more feasible alternative is a generalized Born implicit solvent description which models polar solvent as a dielectric continuum. Unfortunately, the attainable simulation speedup does not transfer to the massive parallel computers often employed for simulation of large structures. Longer cutoff distances, spatially heterogenous distribution of atoms and the necessary three-fold iteration over atom-pairs in each timestep combine to challenge efficient parallel performance of generalized Born implicit solvent algorithms. Here we report how NAMD, a parallel molecular dynamics program, meets the challenge through a unique parallelization strategy. NAMD now permits efficient simulation of large systems whose slow conformational motions benefit most from implicit solvent descriptions due to the inherent low viscosity. NAMD's implicit solvent performance is benchmarked and then illustrated in simulating the ratcheting Escherichia coli ribosome involving ~250,000 atoms.

  12. An Explicit Nonlinear Mapping for Manifold Learning.

    PubMed

    Qiao, Hong; Zhang, Peng; Wang, Di; Zhang, Bo

    2013-02-01

    Manifold learning is a hot research topic in the held of computer science and has many applications in the real world. A main drawback of manifold learning methods is, however, that there are no explicit mappings from the input data manifold to the output embedding. This prohibits the application of manifold learning methods in many practical problems such as classification and target detection. Previously, in order to provide explicit mappings for manifold learning methods, many methods have been proposed to get an approximate explicit representation mapping with the assumption that there exists a linear projection between the high-dimensional data samples and their low-dimensional embedding. However, this linearity assumption may be too restrictive. In this paper, an explicit nonlinear mapping is proposed for manifold learning, based on the assumption that there exists a polynomial mapping between the high-dimensional data samples and their low-dimensional representations. As far as we know, this is the hrst time that an explicit nonlinear mapping for manifold learning is given. In particular, we apply this to the method of locally linear embedding and derive an explicit nonlinear manifold learning algorithm, which is named neighborhood preserving polynomial embedding. Experimental results on both synthetic and real-world data show that the proposed mapping is much more effective in preserving the local neighborhood information and the nonlinear geometry of the high-dimensional data samples than previous work.

  13. Sleep enhances explicit recollection in recognition memory.

    PubMed

    Drosopoulos, Spyridon; Wagner, Ullrich; Born, Jan

    2005-01-01

    Recognition memory is considered to be supported by two different memory processes, i.e., the explicit recollection of information about a previous event and an implicit process of recognition based on an acontextual sense of familiarity. Both types of memory supposedly rely on distinct memory systems. Sleep is known to enhance the consolidation of memories, with the different sleep stages affecting different types of memory. In the present study, we used the process-dissociation procedure to compare the effects of sleep on estimates of explicit (recollection) and implicit (familiarity) memory formation on a word-list discrimination task. Subjects studied two lists of words before a 3-h retention interval of sleep or wakefulness, and recognition was tested afterward. The retention intervals were positioned either in the early night when sleep is dominated by slow-wave sleep (SWS), or in the late night, when sleep is dominated by REM sleep. Sleep enhanced explicit recognition memory, as compared with wakefulness (P < 0.05), whereas familiarity was not affected by sleep. Moreover, explicit recognition was particularly enhanced after sleep in the early-night retention interval, and especially when the words were presented with the same contextual features as during learning, i.e., in the same font (P < 0.05). The data indicate that in a task that allows separating the contribution of explicit and implicit memory, sleep particularly supports explicit memory formation. The mechanism of this effect appears to be linked to SWS.

  14. Safe battery solvents

    DOEpatents

    Harrup, Mason K.; Delmastro, Joseph R.; Stewart, Frederick F.; Luther, Thomas A.

    2007-10-23

    An ion transporting solvent maintains very low vapor pressure, contains flame retarding elements, and is nontoxic. The solvent in combination with common battery electrolyte salts can be used to replace the current carbonate electrolyte solution, creating a safer battery. It can also be used in combination with polymer gels or solid polymer electrolytes to produce polymer batteries with enhanced conductivity characteristics. The solvents may comprise a class of cyclic and acyclic low molecular weight phosphazenes compounds, comprising repeating phosphorus and nitrogen units forming a core backbone and ion-carrying pendent groups bound to the phosphorus. In preferred embodiments, the cyclic phosphazene comprises at least 3 phosphorus and nitrogen units, and the pendent groups are polyethers, polythioethers, polyether/polythioethers or any combination thereof, and/or other groups preferably comprising other atoms from Group 6B of the periodic table of elements.

  15. Separation by solvent extraction

    DOEpatents

    Holt, Jr., Charles H.

    1976-04-06

    17. A process for separating fission product values from uranium and plutonium values contained in an aqueous solution, comprising adding an oxidizing agent to said solution to secure uranium and plutonium in their hexavalent state; contacting said aqueous solution with a substantially water-immiscible organic solvent while agitating and maintaining the temperature at from -1.degree. to -2.degree. C. until the major part of the water present is frozen; continuously separating a solid ice phase as it is formed; separating a remaining aqueous liquid phase containing fission product values and a solvent phase containing plutonium and uranium values from each other; melting at least the last obtained part of said ice phase and adding it to said separated liquid phase; and treating the resulting liquid with a new supply of solvent whereby it is practically depleted of uranium and plutonium.

  16. Solvent resistant copolyimide

    NASA Technical Reports Server (NTRS)

    Chang, Alice C. (Inventor); St. Clair, Terry L. (Inventor)

    1995-01-01

    A solvent resistant copolyimide was prepared by reacting 4,4'-oxydiphthalic anhydride with a diaimine blend comprising, based on the total amount of the diamine blend, about 75 to 90 mole percent of 3,4'-oxydianiline and about 10 to 25 mole percent p-phenylene diamine. The solvent resistant copolyimide had a higher glass transition temperature when cured at 350.degree. , 371.degree. and 400.degree. C. than LaRC.TM.-IA. The composite prepared from the copolyimide had similar mechanical properties to LaRC.TM.-IA. Films prepared from the copolyimide were resistant to immediate breakage when exposed to solvents such as dimethylacetamide and chloroform. The adhesive properties of the copolyimide were maintained even after testing at 23.degree., 150.degree., 177.degree. and 204.degree. C.

  17. Halogenated solvent remediation

    DOEpatents

    Sorenson, Jr., Kent S.

    2008-11-11

    Methods for enhancing bioremediation of ground water contaminated with nonaqueous halogenated solvents are disclosed. An illustrative method includes adding an electron donor for microbe-mediated anaerobic reductive dehalogenation of the halogenated solvents, which electron donor enhances mass transfer of the halogenated solvents from residual source areas into the aqueous phase of the ground water. Illustrative electron donors include C.sub.2-C.sub.4 carboxylic acids and hydroxy acids, salts thereof, esters of C.sub.2-C.sub.4 carboxylic acids and hydroxy acids, and mixtures thereof, of which lactic acid, salts of lactic acid--such as sodium lactate, lactate esters, and mixtures thereof are particularly illustrative. The microbes are either indigenous to the ground water, or such microbes can be added to the ground water in addition to the electron donor.

  18. Halogenated solvent remediation

    DOEpatents

    Sorenson, Kent S.

    2004-08-31

    Methods for enhancing bioremediation of ground water contaminated with nonaqueous halogenated solvents are disclosed. A preferred method includes adding a composition to the ground water wherein the composition is an electron donor for microbe-mediated reductive dehalogenation of the halogenated solvents and enhances mass transfer of the halogenated solvents from residual source areas into the aqueous phase of the ground water. Illustrative compositions effective in these methods include surfactants such as C.sub.2 -C.sub.4 carboxylic acids and hydroxy acids, salts thereof, esters of C.sub.2 -C.sub.4 carboxylic acids and hydroxy acids, and mixtures thereof. Especially preferred compositions for use in these methods include lactic acid, salts of lactic acid, such as sodium lactate, lactate esters, and mixtures thereof. The microbes are either indigenous to the ground water, or such microbes can be added to the ground water in addition to the composition.

  19. Efficient Conformational Sampling in Explicit Solvent Using a Hybrid Replica Exchange Molecular Dynamics Method

    DTIC Science & Technology

    2011-12-01

    radius of gyration (Rg) distributions.17,22 Zhou and Berne showed significant dif- ferences in the free energy landscape of the C-terminal β-hairpin...exchange molecular dynamics simulation method employing the Poisson Boltzmann model. J. Chem. Phys. 2007, 127, 084119–17. (23) Zhou, R.; Berne , B. J...31) Gallicchio, E.; Andrec, M.; Felts, A. K.; Levy , R. M. Tempera- ture weighted histogram analysis method, replica exchange, and transi- tion paths. J. Phys. Chem. B 2005, 109, 6722–6731.

  20. The reorganization energy of electron transfer in nonpolar solvents: Molecular level treatment of the solvent

    NASA Astrophysics Data System (ADS)

    Leontyev, I. V.; Tachiya, M.

    2005-12-01

    The intermolecular electron transfer in a solute pair consisting of pyrene and dimethylaniline is investigated in a nonpolar solvent, n-hexane. The earlier elaborated approach [M. Tachiya, J. Phys Chem. 97, 5911 (1993)] is used; this method provides a physically relevant background for separating inertial and inertialess polarization responses for both nonpolarizable and polarizable molecular level simulations. The molecular-dynamics technique was implemented for obtaining the equilibrium ensemble of solvent configurations. The nonpolar solvent, n-hexane, was treated in terms of OPLS-AA parametrization. Solute Lennard-Jones parameters were taken from the same parametrization. Solute charge distributions of the initial and final states were determined using ab initio level [HF/6-31G(d,p)] quantum-chemical calculations. Configuration analysis was performed explicitly taking into account the anisotropic polarizability of n-hexane. It is shown that the Gaussian law well describes calculated distribution functions of the solvent coordinate, therefore, the rate constant of the ET reaction can be characterized by the reorganization energy. Evaluated values of the reorganization energies are in a range of 0.03-0.11 eV and significant contribution (more then 40% of magnitude) comes from anisotropic polarizability. Investigation of the reorganization energy λ dependence on the solute pair separation distance d revealed unexpected behavior. The dependence has a very sharp peak at the distance d =7Å where solvent molecules are able to penetrate into the intermediate space between the solute pair. The reason for such behavior is clarified. This new effect has a purely molecular origin and cannot be described within conventional continuum solvent models.

  1. The reorganization energy of electron transfer in nonpolar solvents: Molecular level treatment of the solvent

    SciTech Connect

    Leontyev, I.V.; Tachiya, M.

    2005-12-08

    The intermolecular electron transfer in a solute pair consisting of pyrene and dimethylaniline is investigated in a nonpolar solvent, n-hexane. The earlier elaborated approach [M. Tachiya, J. Phys Chem. 97, 5911 (1993)] is used; this method provides a physically relevant background for separating inertial and inertialess polarization responses for both nonpolarizable and polarizable molecular level simulations. The molecular-dynamics technique was implemented for obtaining the equilibrium ensemble of solvent configurations. The nonpolar solvent, n-hexane, was treated in terms of OPLS-AA parametrization. Solute Lennard-Jones parameters were taken from the same parametrization. Solute charge distributions of the initial and final states were determined using ab initio level [HF/6-31G(d,p)] quantum-chemical calculations. Configuration analysis was performed explicitly taking into account the anisotropic polarizability of n-hexane. It is shown that the Gaussian law well describes calculated distribution functions of the solvent coordinate, therefore, the rate constant of the ET reaction can be characterized by the reorganization energy. Evaluated values of the reorganization energies are in a range of 0.03-0.11 eV and significant contribution (more then 40% of magnitude) comes from anisotropic polarizability. Investigation of the reorganization energy {lambda} dependence on the solute pair separation distance d revealed unexpected behavior. The dependence has a very sharp peak at the distance d=7 A where solvent molecules are able to penetrate into the intermediate space between the solute pair. The reason for such behavior is clarified. This new effect has a purely molecular origin and cannot be described within conventional continuum solvent models.

  2. INVESTIGATION OF PLUTONIUM AND URANIUM UPTAKE INTO MCU SOLVENT AND NEXT GENERATION SOLVENT

    SciTech Connect

    Peters, T.; Fink, S.

    2012-01-06

    At the request of the Savannah River Remediation (SRR) customer, the Savannah River National Laboratory (SRNL) examined the plutonium (Pu) and uranium (U) uptake into the Next Generation Solvent (NGS) that will be used at the Salt Waste Processing Facility (SWPF). SRNL examined archived samples of solvent used in Extraction-Scrub-Strip (ESS) tests, as well as samples from new tests designed explicitly to examine the Pu and U uptake. Direct radiocounting for Pu and U provided the best results. Using the radiocounting results, we found that in all cases there were <3.41E-12 g Pu/g of NGS and <1.17E-05 g U/g of NGS in multiple samples, even after extended contact times and high aqueous:organic volume phase ratios. These values are conservative as they do not allow for release or removal of the actinides by scrub, strip, or solvent wash processes. The values do not account for extended use or any increase that may occur due to radiolytic damage of the solvent.

  3. ONSITE SOLVENT RECOVERY

    EPA Science Inventory

    This study evaluated the product quality, waste reduction/pollution prevention, and economic aspects of three technologies for onsite solvent recovery. The technologies were (1) atmospheric batch distillation, (2) vacuum heat-pump distillation, and (3) low-emission vapor degreas...

  4. DESIGNING GREENER SOLVENTS

    EPA Science Inventory

    Computer-aided design of chemicals and chemical mixtures provides a powerful tool to help engineers identify cleaner process designs and more-benign alternatives to toxic industrial solvents. Three software programs are discussed: (1) PARIS II (Program for Assisting the Replaceme...

  5. Organic solvent topical report

    SciTech Connect

    Cowley, W.L.

    1998-04-30

    This report is the technical basis for the accident and consequence analyses used in the Hanford Tank Farms Basis for Interim Operation. The report also contains the scientific and engineering information and reference material needed to understand the organic solvent safety issue. This report includes comments received from the Chemical Reactions Subcommittee of the Tank Advisory Panel.

  6. Organic solvent topical report

    SciTech Connect

    COWLEY, W.L.

    1999-05-13

    This report provides the basis for closing the organic solvent safety issue. Sufficient information is presented to conclude that risk posed by an organic solvent fire is within risk evaluation guidelines. This report updates information contained in Analysis of Consequences of Postulated Solvent Fires in Hanford Site Waste Tanks. WHC-SD-WM-CN-032. Rev. 0A (Cowley et al. 1996). However, this document will not replace Cowley et al (1996) as the primary reference for the Basis for Interim Operation (BIO) until the recently submitted BIO amendment (Hanson 1999) is approved by the US Department of Energy. This conclusion depends on the use of controls for preventing vehicle fuel fires and for limiting the use of flame cutting in areas where hot metal can fall on the waste surface.The required controls are given in the Tank Waste Remediation System Technical Safety Requirements (Noorani 1997b). This is a significant change from the conclusions presented in Revision 0 of this report. Revision 0 of this calcnote concluded that some organic solvent fire scenarios exceeded risk evaluation guidelines, even with controls imposed.

  7. Dehydration-Driven Solvent Exposure of Hydrophobic Surfaces as a Driving Force in Peptide Folding

    SciTech Connect

    Daidone, Isabella; Ulmschneider, Martin; DiNola, Alfredo; Amadei, Andrea; Smith, Jeremy C

    2007-09-01

    Recent work has shown that the nature of hydration of pure hydrophobic surfaces changes with the length scale considered: water hydrogen-bonding networks adapt to small exposed hydrophobic species, hydrating or 'wetting' them at relatively high densities, whereas larger hydrophobic areas are 'dewetted' [Chandler D (2005), Nature 29:640-647]. Here we determine whether this effect is also present in peptides by examining the folding of a {beta}-hairpin (the 14-residue amyloidogenic prion protein H1 peptide), using microsecond time-scale molecular dynamics simulations. Two simulation models are compared, one explicitly including the water molecules, which may thus adapt locally to peptide configurations, and the other using a popular continuum approximation, the generalized Born/surface area implicit solvent model. The results obtained show that, in explicit solvent, peptide conformers with high solvent-accessible hydrophobic surface area indeed also have low hydration density around hydrophobic residues, whereas a concomitant higher hydration density around hydrophilic residues is observed. This dewetting effect stabilizes the fully folded {beta}-hairpin state found experimentally. In contrast, the implicit solvent model destabilizes the fully folded hairpin, tending to cluster hydrophobic residues regardless of the size of the exposed hydrophobic surface. Furthermore, the rate of the conformational transitions in the implicit solvent simulation is almost doubled with respect to that of the explicit solvent. The results suggest that dehydration-driven solvent exposure of hydrophobic surfaces may be a significant factor determining peptide conformational equilibria.

  8. Explicit versus spontaneous diffeomorphism breaking in gravity

    NASA Astrophysics Data System (ADS)

    Bluhm, Robert

    2015-03-01

    Gravitational theories with fixed background fields break local Lorentz and diffeomorphism invariance either explicitly or spontaneously. In the case of explicit breaking it is known that conflicts can arise between the dynamics and geometrical constraints, while spontaneous breaking evades this problem. It is for this reason that in the gravity sector of the Standard-Model extension (SME) it is assumed that the background fields (SME coefficients) originate from spontaneous symmetry breaking. However, in other examples, such as Chern-Simons gravity and massive gravity, diffeomorphism invariance is explicitly broken by the background fields, and the potential conflicts between the dynamics and geometry can be avoided in most cases. An analysis of how this occurs is given, and the conditions that are placed on the metric tensor and gravitational structure as a result of the presence of an explicit-breaking background are described. The gravity sector of the SME is then considered for the case of explicit breaking. However, it is found that a useful post-Newtonian limit is only obtained when the symmetry breaking is spontaneous.

  9. Solvent-Ion Interactions in Salt Water: A Simple Experiment.

    ERIC Educational Resources Information Center

    Willey, Joan D.

    1984-01-01

    Describes a procedurally quick, simple, and inexpensive experiment which illustrates the magnitude and some effects of solvent-ion interactions in aqueous solutions. Theoretical information, procedures, and examples of temperature, volume and hydration number calculations are provided. (JN)

  10. Brain Networks of Explicit and Implicit Learning

    PubMed Central

    Yang, Jing; Li, Ping

    2012-01-01

    Are explicit versus implicit learning mechanisms reflected in the brain as distinct neural structures, as previous research indicates, or are they distinguished by brain networks that involve overlapping systems with differential connectivity? In this functional MRI study we examined the neural correlates of explicit and implicit learning of artificial grammar sequences. Using effective connectivity analyses we found that brain networks of different connectivity underlie the two types of learning: while both processes involve activation in a set of cortical and subcortical structures, explicit learners engage a network that uses the insula as a key mediator whereas implicit learners evoke a direct frontal-striatal network. Individual differences in working memory also differentially impact the two types of sequence learning. PMID:22952624

  11. Spatially explicit analyses unveil density dependence.

    PubMed Central

    Veldtman, Ruan; McGeoch, Melodie A.

    2004-01-01

    Density-dependent processes are fundamental in the understanding of species population dynamics. Whereas the benefits of considering the spatial dimension in population biology are widely acknowledged, the implications of doing so for the statistical detection of spatial density dependence have not been examined. The outcome of traditional tests may therefore differ from those that include ecologically relevant locational information on both the prey species and natural enemy. Here, we explicitly incorporate spatial information on individual counts when testing for density dependence between an insect herbivore and its parasitoids. The spatially explicit approach used identified significant density dependence more frequently and in different instances than traditional methods. The form of density dependence detected also differed between methods. These results demonstrate that the explicit consideration of patch location in density-dependence analyses is likely to significantly alter current understanding of the prevalence and form of spatial density dependence in natural populations. PMID:15590593

  12. Does explicit expectation really affect preparation?

    PubMed

    Umbach, Valentin J; Schwager, Sabine; Frensch, Peter A; Gaschler, Robert

    2012-01-01

    Expectation enables preparation for an upcoming event and supports performance if the anticipated situation occurs, as manifested in behavioral effects (e.g., decreased RT). However, demonstrating coincidence between expectation and preparation is not sufficient for attributing a causal role to the former. The content of explicit expectation may simply reflect the present preparation state. We targeted this issue by experimentally teasing apart demands for preparation and explicit expectations. Expectations often originate from our experience: we expect that events occurring with a high frequency in the past are more likely to occur again. In addition to expectation, other task demands can feed into action preparation. In four experiments, frequency-based expectation was pitted against a selective response deadline. In a three-choice reaction time task, participants responded to stimuli that appeared with varying frequency (60, 30, 10%). Trial-by-trial stimulus expectations were either captured via verbal predictions or induced by visual cues. Predictions as well as response times quickly conformed to the variation in stimulus frequency. After two (of five) experimental blocks we forced participants by selective time pressure to respond faster to a less frequent stimulus. Therefore, participants had to prepare for one stimulus (medium frequency) while often explicitly expecting a different one (high frequency). Response times for the less frequent stimulus decreased immediately, while explicit expectations continued to indicate the (unchanged) presentation frequencies. Explicit expectations were thus not just reflecting preparation. In fact, participants responded faster when the stimulus matched the trial-wise expectations, even when task demands discouraged their use. In conclusion, we argue that explicit expectation feeds into preparatory processes instead of being a mere by-product.

  13. DESIGNING ENVIRONMENTALLY BENIGN SOLVENT SUBSTITUTES

    EPA Science Inventory

    Since the signing of 1987 Montreal Protocol, reducing and eliminating the use of harmful solvents has become an internationally imminent environmental protection mission. Solvent substitution is an effective way to achieve this goal. The Program for Assisting the Replacement of...

  14. Testing the semi-explicit assembly model of aqueous solvation in the SAMPL4 challenge.

    PubMed

    Li, Libo; Dill, Ken A; Fennell, Christopher J

    2014-03-01

    Here, we test a method, called semi-explicit assembly (SEA), that computes the solvation free energies of molecules in water in the SAMPL4 blind test challenge. SEA was developed with the intention of being as accurate as explicit-solvent models, but much faster to compute. It is accurate because it uses pre-simulations of simple spheres in explicit solvent to obtain structural and thermodynamic quantities, and it is fast because it parses solute free energies into regionally additive quantities. SAMPL4 provided us the opportunity to make new tests of SEA. Our tests here lead us to the following conclusions: (1) The newest version, called Field-SEA, which gives improved predictions for highly charged ions, is shown here to perform as well as the earlier versions (dipolar and quadrupolar SEA) on this broad blind SAMPL4 test set. (2) We find that both the past and present SEA models give solvation free energies that are as accurate as TIP3P. (3) Using a new approach for force field parameter optimization, we developed improved hydroxyl parameters that ensure consistency with neat-solvent dielectric constants, and found that they led to improved solvation free energies for hydroxyl-containing compounds in SAMPL4. We also learned that these hydroxyl parameters are not just fixing solvent exposed oxygens in a general sense, and therefore do not improve predictions for carbonyl or carboxylic-acid groups. Other such functional groups will need their own independent optimizations for potential improvements. Overall, these tests in SAMPL4 indicate that SEA is an accurate, general and fast new approach to computing solvation free energies.

  15. Explicit Form Focus Instruction: The Effects on Implicit and Explicit Knowledge of ESL Learners

    ERIC Educational Resources Information Center

    Ebadi, Mandana Rohollahzadeh; Saad, Mohd Rashid Mohd; Abedalaziz, Nabil

    2014-01-01

    The study examines the effect of explicit form focus instruction and specifically metalinguistic information feedback on the development of both implicit and explicit knowledge of adult English as a Second Language (ESL) learners. Ninety-one subjects at the lower intermediate level were carefully selected through placement test at one of the…

  16. Solvent Immersion Imprint Lithography

    SciTech Connect

    Vasdekis, Andreas E.; Wilkins, Michael J.; Grate, Jay W.; Kelly, Ryan T.; Konopka, Allan; Xantheas, Sotiris S.; Chang, M. T.

    2014-06-21

    The mechanism of polymer disolution was explored for polymer microsystem prototyping, including microfluidics and optofluidics. Polymer films are immersed in a solvent, imprinted and finally brought into contact with a non-modified surface to permanently bond. The underlying polymer-solvent interactions were experimentally and theoretically investigated, and enabled rapid polymer microsystem prototyping. During imprinting, small molecule integration in the molded surfaces was feasible, a principle applied to oxygen sensing. Polystyrene (PS) was employed for microbiological studies at extreme environmental conditions. The thermophile anaerobe Clostridium Thermocellum was grown in PS pore-scale micromodels, revealing a double mean generation lifetime than under ideal culture conditions. Microsystem prototyping through directed polymer dissolution is simple and accessible, while simultaneous patterning, bonding, and surface/volume functionalization are possible in less than one minute.

  17. PARIS II: DESIGNING GREENER SOLVENTS

    EPA Science Inventory

    PARIS II (the program for assisting the replacement of industrial solvents, version II), developed at the USEPA, is a unique software tool that can be used for customizing the design of replacement solvents and for the formulation of new solvents. This program helps users avoid ...

  18. Hazardous solvent substitution

    SciTech Connect

    Twitchell, K.E.

    1995-11-01

    Eliminating hazardous solvents is good for the environment, worker safety, and the bottom line. However, even though we are motivated to find replacements, the big question is `What can we use as replacements for hazardous solvents?`You, too, can find replacements for your hazardous solvents. All you have to do is search for them. Search through the vendor literature of hundreds of companies with thousands of products. Ponder the associated material safety data sheets, assuming of course that you can obtain them and, having obtained them, that you can read them. You will want to search the trade magazines and other sources for product reviews. You will want to talk to users about how well the product actually works. You may also want to check US Environmental Protection Agency (EPA) and other government reports for toxicity and other safety information. And, of course, you will want to compare the product`s constituent chemicals with the many hazardous constituency lists to ensure the safe and legal use of the product in your workplace.

  19. Why Explicit Knowledge Cannot Become Implicit Knowledge

    ERIC Educational Resources Information Center

    VanPatten, Bill

    2016-01-01

    In this essay, I review one of the conclusions in Lindseth (2016) published in "Foreign Language Annals." That conclusion suggests that explicit learning and practice (what she called form-focused instruction) somehow help the development of implicit knowledge (or might even become implicit knowledge). I argue for a different…

  20. Children's Tacit and Explicit Understandings of Dinosaurs.

    ERIC Educational Resources Information Center

    Barba, Robertta H.

    The purpose of this cross-age study was to investigate elementary students' (N=120) tacit and explicit understandings of dinosaurs. Detailed analysis of audiotaped interviews of children's performance during a Piagetian-type clinical interview suggests that children's conceptual understandings of dinosaurs are first developed at a tacit level from…

  1. Sleep Enhances Explicit Recollection in Recognition Memory

    ERIC Educational Resources Information Center

    Drosopoulos, Spyridon; Wagner, Ullrich; Born, Jan

    2005-01-01

    Recognition memory is considered to be supported by two different memory processes, i.e., the explicit recollection of information about a previous event and an implicit process of recognition based on a contextual sense of familiarity. Both types of memory supposedly rely on distinct memory systems. Sleep is known to enhance the consolidation of…

  2. Explicit Instruction in Core Reading Programs

    ERIC Educational Resources Information Center

    Reutzel, D. Ray; Child, Angela; Jones, Cindy D.; Clark, Sarah K.

    2014-01-01

    The purpose of this study was to conduct a content analysis of the types and occurrences of explicit instructional moves recommended for teaching five essentials of effective reading instruction in grades 1, 3, and 5 core reading program teachers' editions in five widely marketed core reading programs. Guided practice was the most frequently…

  3. From Asking to Answering: Making Questions Explicit

    ERIC Educational Resources Information Center

    Washington, Gene

    2006-01-01

    "From Asking To Answering: Making Questions Explicit" describes a pedagogical procedure the author has used in writing classes (expository, technical and creative) to help students better understand the purpose, and effect, of text-questions. It accomplishes this by means of thirteen discrete categories (e.g., CLAIMS, COMMITMENT, ANAPHORA, or…

  4. Uncertainty in spatially explicit animal dispersal models

    USGS Publications Warehouse

    Mooij, Wolf M.; DeAngelis, Donald L.

    2003-01-01

    Uncertainty in estimates of survival of dispersing animals is a vexing difficulty in conservation biology. The current notion is that this uncertainty decreases the usefulness of spatially explicit population models in particular. We examined this problem by comparing dispersal models of three levels of complexity: (1) an event-based binomial model that considers only the occurrence of mortality or arrival, (2) a temporally explicit exponential model that employs mortality and arrival rates, and (3) a spatially explicit grid-walk model that simulates the movement of animals through an artificial landscape. Each model was fitted to the same set of field data. A first objective of the paper is to illustrate how the maximum-likelihood method can be used in all three cases to estimate the means and confidence limits for the relevant model parameters, given a particular set of data on dispersal survival. Using this framework we show that the structure of the uncertainty for all three models is strikingly similar. In fact, the results of our unified approach imply that spatially explicit dispersal models, which take advantage of information on landscape details, suffer less from uncertainly than do simpler models. Moreover, we show that the proposed strategy of model development safeguards one from error propagation in these more complex models. Finally, our approach shows that all models related to animal dispersal, ranging from simple to complex, can be related in a hierarchical fashion, so that the various approaches to modeling such dispersal can be viewed from a unified perspective.

  5. SOLVENT FIRE BY-PRODUCTS

    SciTech Connect

    Walker, D; Samuel Fink, S

    2006-05-22

    Southwest Research Institute (SwRI) conducted a burn test of the Caustic-Side Solvent Extraction (CSSX) solvent to determine the combustion products. The testing showed hydrogen fluoride gas is not a combustion product from a solvent fire when up to 70% of the solvent is consumed. The absence of HF in the combustion gases may reflect concentration of the modifier containing the fluoride groups in the unburned portion. SwRI reported results for other gases (CO, HCN, NOx, formaldehyde, and hydrocarbons). The results, with other supporting information, can be used for evaluating the consequences of a facility fire involving the CSSX solvent inventory.

  6. Solvent replacement for green processing.

    PubMed Central

    Sherman, J; Chin, B; Huibers, P D; Garcia-Valls, R; Hatton, T A

    1998-01-01

    The implementation of the Montreal Protocol, the Clean Air Act, and the Pollution Prevention Act of 1990 has resulted in increased awareness of organic solvent use in chemical processing. The advances made in the search to find "green" replacements for traditional solvents are reviewed, with reference to solvent alternatives for cleaning, coatings, and chemical reaction and separation processes. The development of solvent databases and computational methods that aid in the selection and/or design of feasible or optimal environmentally benign solvent alternatives for specific applications is also discussed. Images Figure 2 Figure 3 PMID:9539018

  7. Molecular modelling of protein-protein/protein-solvent interactions

    NASA Astrophysics Data System (ADS)

    Luchko, Tyler

    The inner workings of individual cells are based on intricate networks of protein-protein interactions. However, each of these individual protein interactions requires a complex physical interaction between proteins and their aqueous environment at the atomic scale. In this thesis, molecular dynamics simulations are used in three theoretical studies to gain insight at the atomic scale about protein hydration, protein structure and tubulin-tubulin (protein-protein) interactions, as found in microtubules. Also presented, in a fourth project, is a molecular model of solvation coupled with the Amber molecular modelling package, to facilitate further studies without the need of explicitly modelled water. Basic properties of a minimally solvated protein were calculated through an extended study of myoglobin hydration with explicit solvent, directly investigating water and protein polarization. Results indicate a close correlation between polarization of both water and protein and the onset of protein function. The methodology of explicit solvent molecular dynamics was further used to study tubulin and microtubules. Extensive conformational sampling of the carboxy-terminal tails of 8-tubulin was performed via replica exchange molecular dynamics, allowing the characterisation of the flexibility, secondary structure and binding domains of the C-terminal tails through statistical analysis methods. Mechanical properties of tubulin and microtubules were calculated with adaptive biasing force molecular dynamics. The function of the M-loop in microtubule stability was demonstrated in these simulations. The flexibility of this loop allowed constant contacts between the protofilaments to be maintained during simulations while the smooth deformation provided a spring-like restoring force. Additionally, calculating the free energy profile between the straight and bent tubulin configurations was used to test the proposed conformational change in tubulin, thought to cause microtubule

  8. Solvent Fractionation of Lignin

    SciTech Connect

    Chatterjee, Sabornie; Saito, Tomonori

    2014-01-01

    Lignin is a highly abundant source of renewable carbon that can be considered as a valuable sustainable source of biobased materials. The major issues for the commercial production of value added high performance lignin products are lignin s physical and chemical heterogenities. To overcome these problems, a variety of procedures have been developed to produce pure lignin suitable for high performace applications such as lignin-derived carbon materials. However, most of the isolation procedures affect lignin s properties and structure. In this chapter, a short review of the effect of solvent fractionation on lignin s properties and structure is presented.

  9. Psychometric intelligence dissociates implicit and explicit learning.

    PubMed

    Gebauer, Guido F; Mackintosh, Nicholas J

    2007-01-01

    The hypothesis that performance on implicit learning tasks is unrelated to psychometric intelligence was examined in a sample of 605 German pupils. Performance in artificial grammar learning, process control, and serial learning did not correlate with various measures of intelligence when participants were given standard implicit instructions. Under an explicit rule discovery instruction, however, a significant relationship between performance on the learning tasks and intelligence appeared. This finding provides support for Reber's hypothesis that implicit learning, in contrast to explicit learning, is independent of intelligence, and confirms thereby the distinction between the 2 modes of learning. However, because there were virtually no correlations among the 3 learning tasks, the assumption of a unitary ability of implicit learning was not supported.

  10. Teleoperations with shared explicit contact force control

    NASA Astrophysics Data System (ADS)

    Caiti, Andrea; Cannata, Giorgio; Casalino, Giuseppe; Reto, Simone

    1997-12-01

    In this paper the development of a master-slave robotics system is presented. This development is part of a research project devoted to the intelligent automation of in-service inspection of welded seams in nuclear plants using non- destructive ultrasonic based techniques. The main feature of the system is a shared explicit control scheme of the contact force during the interaction of the end-effector with the remote environment. This unilateral master-slave operational scheme does not suffer from the drawbacks of the bilateral force reflection based implementation. Moreover it avoids the operator from damaging the remote manipulator during wrong maneuvers due to imperfect video feedback. The paper describes the control structure applied (belonging to the class of explicit force control) and the hardware-software architecture of the system. Experimental results are given on the Ansaldo Olasand manipulator.

  11. Extrapolated stabilized explicit Runge-Kutta methods

    NASA Astrophysics Data System (ADS)

    Martín-Vaquero, J.; Kleefeld, B.

    2016-12-01

    Extrapolated Stabilized Explicit Runge-Kutta methods (ESERK) are proposed to solve multi-dimensional nonlinear partial differential equations (PDEs). In such methods it is necessary to evaluate the function nt times per step, but the stability region is O (nt2). Hence, the computational cost is O (nt) times lower than for a traditional explicit algorithm. In that way stiff problems can be integrated by the use of simple explicit evaluations in which case implicit methods usually had to be used. Therefore, they are especially well-suited for the method of lines (MOL) discretizations of parabolic nonlinear multi-dimensional PDEs. In this work, first s-stages first-order methods with extended stability along the negative real axis are obtained. They have slightly shorter stability regions than other traditional first-order stabilized explicit Runge-Kutta algorithms (also called Runge-Kutta-Chebyshev codes). Later, they are used to derive nt-stages second- and fourth-order schemes using Richardson extrapolation. The stability regions of these fourth-order codes include the interval [ - 0.01nt2, 0 ] (nt being the number of total functions evaluations), which are shorter than stability regions of ROCK4 methods, for example. However, the new algorithms neither suffer from propagation of errors (as other Runge-Kutta-Chebyshev codes as ROCK4 or DUMKA) nor internal instabilities. Additionally, many other types of higher-order (and also lower-order) methods can be obtained easily in a similar way. These methods also allow adaptation of the length step with no extra cost. Hence, the stability domain is adapted precisely to the spectrum of the problem at the current time of integration in an optimal way, i.e., with minimal number of additional stages. We compare the new techniques with other well-known algorithms with good results in very stiff diffusion or reaction-diffusion multi-dimensional nonlinear equations.

  12. Solvent effects on global reactivity properties for neutral and charged systems using the sequential Monte Carlo quantum mechanics model.

    PubMed

    Jaramillo, Paula; Pérez, Patricia; Fuentealba, Patricio; Canuto, Sylvio; Coutinho, Kaline

    2009-04-02

    The energy of the frontier molecular orbitals and reactivity indices such as chemical potential, hardness, and electrophilicity of neutral and charged molecules have been investigated in aqueous solution using explicit model for the solvent with the sequential Monte Carlo/quantum mechanics methodology. The supermolecular structures of the solute-solvent system were generated by Monte Carlo simulation. Statistically uncorrelated structures have been extracted for quantum mechanical calculations of the solute surrounded by the first solvation shell, using explicit water molecules, and the second and third shells as atomic point charges. The supermolecular calculations treating both the solute and the solvent explicitly were performed within density functional theory. The solvent dependence of the frontier molecular orbital energies was analyzed and used to calculate the reactivity indices in solution. The dependence of the results with respect to the number of explicit solvent molecules is also analyzed. It is seen that for the systems considered here, the energies of the highest occupied molecular orbital and the lowest unoccupied molecular orbital show a strong dependence with the number of solvent molecules. However, the properties derived from these are relatively stable. In particular, the results reported here for the reactivity indices obtained using the first solvation shell are similar to those obtained for the limit bulk value. For comparison, the reactivity indices were also calculated in the gas phase and using the polarizable continuum model (PCM). As frequently reported in the literature, neutral molecules do not show significant changes in the reactivity indices between gas phase and the PCM model. However, with the explicit solvent model some important changes were observed: a larger negative chemical potential, a smaller hardness, and a larger electrophilicity. The stabilization of an anion corresponding to a negative chemical potential is obtained

  13. Solvent Blending Strategy to Upgrade MCU CSSX Solvent to Equivalent Next-Generation CSSX Solvent

    SciTech Connect

    Delmau, Laetitia Helene; Moyer, Bruce A

    2012-12-01

    The results of the present study have validated an equal-volume blending strategy for upgrading freshly prepared CSSX solvent to a blended solvent functionally equivalent to NG-CSSX solvent. It is shown that blending fresh CSSX solvent as currently used in MCU with an equal volume of an NG-CSSX solvent concentrate of appropriate composition yields a blended solvent composition (46.5 mM of MaxCalix, 3.5 mM of BOBCalixC6, 0.5 M of Cs-7SB, 3 mM of guanidine suppressor, and 1.5 mM of TOA in Isopar L) that exhibits equivalent batch ESS performance to that of the NG-CSSX solvent containing 50 mM of MaxCalix, 0.5 M of Cs-7SB, and 3 mM of guanidine suppressor in Isopar L. The solvent blend composition is robust to third-phase formation. Results also show that a blend containing up to 60% v/v of CSSX solvent could be accommodated with minimal risk. Extraction and density data for the effect of solvent concentration mimicking diluent evaporation or over-dilution of the equal-volume blended solvent are also given, providing input for setting operational limits. Given that the experiments employed all pristine chemicals, the results do not qualify a blended solvent starting with actual used MCU solvent, which can be expected to have undergone some degree of degradation. Consequently, further work should be considered to evaluate this risk and implement appropriate remediation if needed.

  14. Are mixed explicit/implicit solvation models reliable for studying phosphate hydrolysis? A comparative study of continuum, explicit and mixed solvation models.

    SciTech Connect

    Kamerlin, Shina C. L.; Haranczyk, Maciej; Warshel, Arieh

    2009-05-01

    Phosphate hydrolysis is ubiquitous in biology. However, despite intensive research on this class of reactions, the precise nature of the reaction mechanism remains controversial. In this work, we have examined the hydrolysis of three homologous phosphate diesters. The solvation free energy was simulated by means of either an implicit solvation model (COSMO), hybrid quantum mechanical / molecular mechanical free energy perturbation (QM/MM-FEP) or a mixed solvation model in which N water molecules were explicitly included in the ab initio description of the reacting system (where N=1-3), with the remainder of the solvent being implicitly modelled as a continuum. Here, both COSMO and QM/MM-FEP reproduce Delta Gobs within an error of about 2kcal/mol. However, we demonstrate that in order to obtain any form of reliable results from a mixed model, it is essential to carefully select the explicit water molecules from short QM/MM runs that act as a model for the true infinite system. Additionally, the mixed models tend to be increasingly inaccurate the more explicit water molecules are placed into the system. Thus, our analysis indicates that this approach provides an unreliable way for modelling phosphate hydrolysis in solution.

  15. Sleep promotes offline enhancement of an explicitly learned discrete but not an explicitly learned continuous task

    PubMed Central

    Siengsukon, Catherine F; Al-Sharman, Alham

    2011-01-01

    Background Healthy young individuals benefit from sleep to promote offline enhancement of a variety of explicitly learned discrete motor tasks. It remains unknown if sleep will promote learning of other types of explicit tasks. The purpose of this study is to verify the role of sleep in learning an explicitly instructed discrete motor task and to determine if participants who practice an explicitly instructed continuous tracking task demonstrate sleep-dependent offline learning of this task. Methods In experiment 1, 28 healthy young adults (mean age 25.6 ± 3.8 years) practiced a serial reaction time (SRT) task at either 8 am (SRT no-sleep group) or 8 pm (SRT sleep group) and underwent retention testing 12 ± 1 hours later. In experiment 2, 20 healthy young individuals (mean age 25.6 ± 3.3 years) practiced a continuous tracking task and were similarly divided into a no-sleep (continuous tracking no-sleep group) or sleep group (continuous tracking sleep group). Individuals in both experiments were provided with explicit instruction on the presence of a sequence in their respective task prior to practice. Results Individuals in the SRT sleep group demonstrated a significant offline reduction in reaction time whereas the SRT no-sleep group did not. Results for experiment 1 provide concurrent evidence that explicitly learned discrete tasks undergo sleep-dependent offline enhancement. Individuals in the continuous tracking sleep group failed to demonstrate a significant offline reduction in tracking error. However, the continuous tracking no-sleep group did demonstrate a significant offline improvement in performance. Results for experiment 2 indicate that sleep is not critical for offline enhancement of an explicit learned continuous task. Conclusion The findings that individuals who practiced an explicitly instructed discrete task experienced sleep-dependent offline learning while those individuals who practiced an explicitly instructed continuous task did not may be

  16. Explicit field realizations of W algebras

    NASA Astrophysics Data System (ADS)

    Wei, Shao-Wen; Liu, Yu-Xiao; Zhang, Li-Jie; Ren, Ji-Rong

    2009-06-01

    The fact that certain nonlinear W2,s algebras can be linearized by the inclusion of a spin-1 current can provide a simple way to realize W2,s algebras from linear W1,2,s algebras. In this paper, we first construct the explicit field realizations of linear W1,2,s algebras with double scalar and double spinor, respectively. Then, after a change of basis, the realizations of W2,s algebras are presented. The results show that all these realizations are Romans-type realizations.

  17. Explicit 3-D Hydrodynamic FEM Program

    SciTech Connect

    2000-11-07

    DYNA3D is a nonlinear explicit finite element code for analyzing 3-D structures and solid continuum. The code is vectorized and available on several computer platforms. The element library includes continuum, shell, beam, truss and spring/damper elements to allow maximum flexibility in modeling physical problems. Many materials are available to represent a wide range of material behavior, including elasticity, plasticity, composites, thermal effects and rate dependence. In addition, DYNA3D has a sophisticated contact interface capability, including frictional sliding, single surface contact and automatic contact generation.

  18. Femtosecond transient dichroism/birefringence studies of solute- solvent friction and solvent dynamics

    SciTech Connect

    Chang, Y.J.; Castner, E.W. Jr.; Konitsky, W.; Waldeck, D.H.

    1994-02-01

    Ultrafast, heterodyne, polarization spectroscopies are used to measure solute-solvent frictional coupling and characterize the neat solvent`s relaxation dynamics on femtosecond and picosecond timescales.

  19. Explicitly represented polygon wall boundary model for the explicit MPS method

    NASA Astrophysics Data System (ADS)

    Mitsume, Naoto; Yoshimura, Shinobu; Murotani, Kohei; Yamada, Tomonori

    2015-05-01

    This study presents an accurate and robust boundary model, the explicitly represented polygon (ERP) wall boundary model, to treat arbitrarily shaped wall boundaries in the explicit moving particle simulation (E-MPS) method, which is a mesh-free particle method for strong form partial differential equations. The ERP model expresses wall boundaries as polygons, which are explicitly represented without using the distance function. These are derived so that for viscous fluids, and with less computational cost, they satisfy the Neumann boundary condition for the pressure and the slip/no-slip condition on the wall surface. The proposed model is verified and validated by comparing computed results with the theoretical solution, results obtained by other models, and experimental results. Two simulations with complex boundary movements are conducted to demonstrate the applicability of the E-MPS method to the ERP model.

  20. Spatially explicit modelling of cholera epidemics

    NASA Astrophysics Data System (ADS)

    Finger, F.; Bertuzzo, E.; Mari, L.; Knox, A. C.; Gatto, M.; Rinaldo, A.

    2013-12-01

    Epidemiological models can provide crucial understanding about the dynamics of infectious diseases. Possible applications range from real-time forecasting and allocation of health care resources to testing alternative intervention mechanisms such as vaccines, antibiotics or the improvement of sanitary conditions. We apply a spatially explicit model to the cholera epidemic that struck Haiti in October 2010 and is still ongoing. The dynamics of susceptibles as well as symptomatic and asymptomatic infectives are modelled at the scale of local human communities. Dissemination of Vibrio cholerae through hydrological transport and human mobility along the road network is explicitly taken into account, as well as the effect of rainfall as a driver of increasing disease incidence. The model is calibrated using a dataset of reported cholera cases. We further model the long term impact of several types of interventions on the disease dynamics by varying parameters appropriately. Key epidemiological mechanisms and parameters which affect the efficiency of treatments such as antibiotics are identified. Our results lead to conclusions about the influence of different intervention strategies on the overall epidemiological dynamics.

  1. Fully explicit algorithms for fluid simulation

    NASA Astrophysics Data System (ADS)

    Clausen, Jonathan

    2011-11-01

    Computing hardware is trending towards distributed, massively parallel architectures in order to achieve high computational throughput. For example, Intrepid at Argonne uses 163,840 cores, and next generation machines, such as Sequoia at Lawrence Livermore, will use over one million cores. Harnessing the increasingly parallel nature of computational resources will require algorithms that scale efficiently on these architectures. The advent of GPU-based computation will serve to accelerate this behavior, as a single GPU contains hundreds of processor ``cores.'' Explicit algorithms avoid the communication associated with a linear solve, thus parallel scalability of these algorithms is typically high. This work will explore the efficiency and accuracy of three explicit solution methodologies for the Navier-Stokes equations: traditional artificial compressibility schemes, the lattice-Boltzmann method, and the recently proposed kinetically reduced local Navier-Stokes equations [Borok, Ansumali, and Karlin (2007)]. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  2. SOLVENT EXTRACTION OF URANIUM VALUES

    DOEpatents

    Feder, H.M.; Ader, M.; Ross, L.E.

    1959-02-01

    A process is presented for extracting uranium salt from aqueous acidic solutions by organic solvent extraction. It consists in contacting the uranium bearing solution with a water immiscible dialkylacetamide having at least 8 carbon atoms in the molecule. Mentioned as a preferred extractant is dibutylacetamide. The organic solvent is usually used with a diluent such as kerosene or CCl/sub 4/.

  3. Supercritical multicomponent solvent coal extraction

    NASA Technical Reports Server (NTRS)

    Corcoran, W. H.; Fong, W. S.; Pichaichanarong, P.; Chan, P. C. F.; Lawson, D. D. (Inventor)

    1983-01-01

    The yield of organic extract from the supercritical extraction of coal with larger diameter organic solvents such as toluene is increased by use of a minor amount of from 0.1 to 10% by weight of a second solvent such as methanol having a molecular diameter significantly smaller than the average pore diameter of the coal.

  4. Solvent degradation products in nuclear fuel processing solvents

    SciTech Connect

    Shook, H.E. Jr.

    1988-06-01

    The Savannah River Plant uses a modified Purex process to recover enriched uranium and separate fission products. This process uses 7.5% tri-n-butyl phosphate (TBP) dissolved in normal paraffin hydrocarbons for the solvent extraction of a nitric acid solution containing the materials to be separated. Periodic problems in product decontamination result from solvent degradation. A study to improve process efficiency has identified certain solvent degradation products and suggested mitigation measures. Undecanoic acid, lauric acid, and tridecanoic acid were tentatively identified as diluent degradation products in recycle solvent. These long-chain organic acids affect phase separation and lead to low decontamination factors. Solid phase extraction (SPE) was used to concentrate the organic acids in solvent prior to analysis by high performance liquid chromatography (HPLC). SPE and HPLC methods were optimized in this work for analysis of decanoic acid, undecanoic acid, and lauric acid in solvent. Accelerated solvent degradation studies with 7.5% TBP in normal paraffin hydrocarbons showed that long-chain organic acids and long-chain alkyl butyl phosphoric acids are formed by reactions with nitric acid. Degradation of both tributyl phosphate and hydrocarbon can be minimized with purified normal paraffin replacing the standard grade presently used. 12 refs., 1 fig., 3 tabs.

  5. Switchable Polarity Solvents: Are They Green?

    NASA Astrophysics Data System (ADS)

    Plaumann, Heinz

    2017-03-01

    Solvents play an incredibly important role in large scale chemical reactions. Switchable polarity solvents may prove to be a class of solvent that offers energy and material efficiencies greater than existing solvents. This paper examines such solvents and their potential in a variety of chemical reactions.

  6. COMPUTER AIDED SOLVENT DESIGN FOR THE ENVIRONMENT

    EPA Science Inventory

    Solvent substitution is an effective and useful means of eliminating the use of harmful solvents, but finding substitute solvents which are less harmful and as effective as currently used solvents presents significant difficulties. Solvent substitution is a form of reverse engin...

  7. Developmental Comparisons of Implicit and Explicit Language Learning

    ERIC Educational Resources Information Center

    Lichtman, Karen

    2013-01-01

    Conventional wisdom holds that children learn languages implicitly whereas older learners learn languages explicitly, and some have claimed that after puberty only explicit language learning is possible. However, older learners often receive more explicit instruction than child L2 learners, which may affect their learning strategies. This study…

  8. Positive Evidence Versus Explicit Rule Presentation and Explicit Negative Feedback: A Computer-Assisted Study

    ERIC Educational Resources Information Center

    Sanz, Cristina; Morgan-Short, Kara

    2004-01-01

    The facilitative role of explicit information in second language acquisition has been supported by a significant body of research (Alanen, 1995; Carroll & Swain, 1993; de Graaff, 1997; DeKeyser, 1995; Ellis, 1993; Robinson, 1996, 1997), but counterevidence is also available (Rosa & ONeill, 1999; VanPatten & Oikkenon, 1996). This experimental study…

  9. Making explicit the contention in hospice care.

    PubMed

    Moon, Paul J

    At the core of hospice remains the defining nature of mortals tending to other mortals facing diagnosed terminality. Such situations are pregnant with meanings. As mortals are subjective beings, social engagements become inundated with meaning differences. This alludes to the inescapable occurrence of collisions and conflicts in meaning. It would behoove us to make explicit the contention that exists in hospice care, given that death is the nonnegotiable outcome to be diversely faced by all involved persons whose lived approaches related to death issues may characteristically lack unanimity. Toward elucidating the inherently contentious nature of hospice care, the dynamical influence of external forces that overlie thanatological matters in society and the complex human dynamic in hospice care situations are discussed. Practice suggestions for hospice staff are offered.

  10. Explicit 2-D Hydrodynamic FEM Program

    SciTech Connect

    Lin, Jerry

    1996-08-07

    DYNA2D* is a vectorized, explicit, two-dimensional, axisymmetric and plane strain finite element program for analyzing the large deformation dynamic and hydrodynamic response of inelastic solids. DYNA2D* contains 13 material models and 9 equations of state (EOS) to cover a wide range of material behavior. The material models implemented in all machine versions are: elastic, orthotropic elastic, kinematic/isotropic elastic plasticity, thermoelastoplastic, soil and crushable foam, linear viscoelastic, rubber, high explosive burn, isotropic elastic-plastic, temperature-dependent elastic-plastic. The isotropic and temperature-dependent elastic-plastic models determine only the deviatoric stresses. Pressure is determined by one of 9 equations of state including linear polynomial, JWL high explosive, Sack Tuesday high explosive, Gruneisen, ratio of polynomials, linear polynomial with energy deposition, ignition and growth of reaction in HE, tabulated compaction, and tabulated.

  11. Solvent extraction of lubricating oils

    SciTech Connect

    Sequeira, A. Jr.

    1991-08-13

    This patent describes improvement in a process for solvent refining a hydrocarbon based lubricating oil stock containing aromatics and non-aromatics components with an extraction solvent wherein the lubricating oil stock is contacted with the extraction solvent in a first extraction zone at a first extraction temperature in the range of 100{degrees} F to 250{degrees} F and a solvent to oil dosage in the range of 75 to 500 vol % forming an aromatics-rich primary extract and an aromatics-lean primary raffinate of high viscosity index of at least 85. The improvement comprises: withdrawing and cooling the primary extract to a temperature 10{degrees} F to 120{degrees} F below the extraction temperature and admixing with 0.0 vol % to 10 vol % anti-solvent thereby forming a secondary extract and a secondary raffinate, passing the secondary raffinate to a second extraction zone wherein the secondary raffinate is contacted with the extraction solvent at a second extraction temperature in the range of 100{degrees} F to 250{degrees} F and solvent to oil dosage in the range of 75 to 500 vol %, to form an aromatics-lean tertiary raffinate phase of viscosity index 65 or greater.

  12. Swelling of lignites in organic solvents

    SciTech Connect

    R.G. Makitra; D.V. Bryk

    2008-10-15

    Data on the swelling of Turkish lignites can be summarized using linear multiparameter equations that take into account various properties of solvents. Factors responsible for the amounts of absorbed solvents are the basicity and cohesion energy density of the solvents.

  13. Critical Casimir interactions and colloidal self-assembly in near-critical solvents.

    PubMed

    Tasios, Nikos; Edison, John R; van Roij, René; Evans, Robert; Dijkstra, Marjolein

    2016-08-28

    A binary solvent mixture close to critical demixing experiences fluctuations whose correlation length, ξ, diverges as the critical point is approached. The solvent-mediated (SM) interaction that arises between a pair of colloids immersed in such a near-critical solvent can be long-ranged and this so-called critical Casimir interaction is well-studied. How a (dense) suspension of colloids will self-assemble under these conditions is poorly understood. Using a two-dimensional lattice model for the solvent and hard disks to represent the colloids, we perform extensive Monte Carlo simulations to investigate the phase behaviour of this model colloidal suspension as a function of colloid size and wettability under conditions where the solvent reservoir is supercritical. Unlike most other approaches, where the solvent is modelled as an implicit background, our model employs an explicit solvent and treats the suspension as a ternary mixture. This enables us to capture important features, including the pronounced fractionation of the solvent in the coexisting colloidal phases, of this complex system. We also present results for the partial structure factors; these shed light on the critical behaviour in the ternary mixture. The degree to which an effective two-body pair potential description can describe the phase behaviour and structure of the colloidal suspension is discussed briefly.

  14. Reformulation of Maxwell's equations to incorporate near-solute solvent structure.

    PubMed

    Yang, Pei-Kun; Lim, Carmay

    2008-09-04

    Maxwell's equations, which treat electromagnetic interactions between macroscopic charged objects in materials, have explained many phenomena and contributed to many applications in our lives. Derived in 1861 when no methods were available to determine the atomic structure of macromolecules, Maxwell's equations assume the solvent to be a structureless continuum. However, near-solute solvent molecules are highly structured, unlike far-solute bulk solvent molecules. Current methods cannot treat both the near-solute solvent structure and time-dependent electromagnetic interactions in a macroscopic system. Here, we derive "microscopic" electrodynamics equations that can treat macroscopic time-dependent electromagnetic field problems like Maxwell's equations and reproduce the solvent molecular and dipole density distributions observed in molecular dynamics simulations. These equations greatly reduce computational expense by not having to include explicit solvent molecules, yet they treat the solvent electrostatic and van der Waals effects more accurately than continuum models. They provide a foundation to study electromagnetic interactions between molecules in a macroscopic system that are ubiquitous in biology, bioelectromagnetism, and nanotechnology. The general strategy presented herein to incorporate the near-solute solvent structure would enable studies on how complex cellular protein-ligand interactions are affected by electromagnetic radiation, which could help to prevent harmful electromagnetic spectra or find potential therapeutic applications.

  15. Molecular modeling of the binding modes of the iron-sulfur protein to the Jac1 co-chaperone from Saccharomyces cerevisiae by all-atom and coarse-grained approaches.

    PubMed

    Mozolewska, Magdalena A; Krupa, Paweł; Scheraga, Harold A; Liwo, Adam

    2015-08-01

    The iron-sulfur protein 1 (Isu1) and the J-type co-chaperone Jac1 from yeast are part of a huge ATP-dependent system, and both interact with Hsp70 chaperones. Interaction of Isu1 and Jac1 is a part of the iron-sulfur cluster biogenesis system in mitochondria. In this study, the structure and dynamics of the yeast Isu1-Jac1 complex has been modeled. First, the complete structure of Isu1 was obtained by homology modeling using the I-TASSER server and YASARA software and thereafter tested for stability in the all-atom force field AMBER. Then, the known experimental structure of Jac1 was adopted to obtain initial models of the Isu1-Jac1 complex by using the ZDOCK server for global and local docking and the AutoDock software for local docking. Three most probable models were subsequently subjected to the coarse-grained molecular dynamics simulations with the UNRES force field to obtain the final structures of the complex. In the most probable model, Isu1 binds to the left face of the Γ-shaped Jac1 molecule by the β-sheet section of Isu1. Residues L105 , L109 , and Y163 of Jac1 have been assessed by mutation studies to be essential for binding (Ciesielski et al., J Mol Biol 2012; 417:1-12). These residues were also found, by UNRES/molecular dynamics simulations, to be involved in strong interactions between Isu1 and Jac1 in the complex. Moreover, N(95), T(98), P(102), H(112), V(159), L(167), and A(170) of Jac1, not yet tested experimentally, were also found to be important in binding.

  16. Molecular modeling of the binding modes of the Iron-sulfur protein to the Jac1 co-chaperone from Saccharomyces cerevisiae by all-atom and coarse-grained approaches

    PubMed Central

    Mozolewska, Magdalena A.; Krupa, Paweł; Scheraga, Harold A.; Liwo, Adam

    2015-01-01

    The Iron sulfur protein 1 (Isu1) from yeast, and the J-type co-chaperone Jac1, are part of a huge ATP-dependent system, and both interact with Hsp70 chaperones. Interaction of Isu1 and Jac1 is a part of the iron-sulfur cluster biogenesis system in mitochondria. In this study, the structure and dynamics of the yeast Isu1-Jac1 complex has been modeled. First, the complete structure of Isu1 was obtained by homology modeling using the I-TASSER server and YASARA software and thereafter tested for stability in the all-atom force field AMBER. Then, the known experimental structure of Jac1 was adopted to obtain initial models of the Isu1-Jac1 complex by using the ZDOCK server for global and local docking and the AutoDock software for local docking. Three most probable models were subsequently subjected to the coarse-grained molecular dynamics simulations with the UNRES force field to obtain the final structures of the complex. In the most probable model, Isu1 binds to the left face of the “Γ” shaped Jac1 molecule by the β-sheet section of Isu1. Residues L105, L109, and Y163 of Jac1 have been assessed by mutation studies to be essential for binding (Ciesielski et al., J. Mol. Biol. 2012, 417, 1–12). These residues were also found, by UNRES/MD simulations, to be involved in strong interactions between Isu1 and Jac1 in the complex. Moreover, N95, T98, P102, H112, V159, L167 and A170 of Jac1, not yet tested experimentally, were also found important in binding. PMID:25973573

  17. ON-SITE SOLVENT RECOVERY

    EPA Science Inventory

    This study evaluated the product quality, waste reduction/pollution prevention, and economic aspects of three technologies for onsite solvent recovery: atmospheric batch distillation, vacuum heat-pump distillation, and low-emission vapor degreasing. The atmospheric and vacuum ...

  18. RESIDUAL RISK ASSESSMENT: HALOGENATED SOLVENTS

    EPA Science Inventory

    This source category previously subjected to a technology-based standard will be examined to determine if health or ecological risks are significant enough to warrant further regulation for Halogenated Solvent Degreasing Facilities. These assessments utilize existing models and d...

  19. SOLV-DB: Solvents Data

    DOE Data Explorer

    SOLV-DB provides a specialized mix of information on commercially available solvents. The development of the database was funded under the Strategic Environmental Research and Development Program (SERDP) with funds from EPA and DOE's Office of Industrial Technologies in EE. The information includes: • Health and safety considerations involved in choosing and using solvents • Chemical and physical data affecting the suitability of a particular solvent for a wide range of potential applications • Regulatory responsibilities, including exposure and effluent limits, hazard classification status with respect to several key statutes, and selected reporting requirements • Environmental fate data, to indicate whether a solvent is likely to break down or persist in air or water, and what types of waste treatment techniques may apply to it • CAS numbers (from Chemical Abstracts Service) and Sax Numbers (from Sax, et.al., Dangerous Properties of Industrial Materials) Supplier Information See help information at http://solvdb.ncms.org/welcome.htm (Specialized Interface)

  20. Applied biotransformations in green solvents.

    PubMed

    Hernáiz, María J; Alcántara, Andrés R; García, José I; Sinisterra, José V

    2010-08-16

    The definite interest in implementing sustainable industrial technologies has impelled the use of biocatalysts (enzymes or cells), leading to high chemo-, regio- and stereoselectivities under mild conditions. As usual substrates are not soluble in water, the employ of organic solvents is mandatory. We will focus on different attempts to combine the valuable properties of green solvents with the advantages of using biocatalysts for developing cleaner synthetic processes.

  1. Reactive Force Fields via Explicit Valency

    NASA Astrophysics Data System (ADS)

    Kale, Seyit

    Computational simulations are invaluable in elucidating the dynamics of biological macromolecules. Unfortunately, reactions present a fundamental challenge. Calculations based on quantum mechanics can predict bond formation and rupture; however they suffer from severe length- and time-limitations. At the other extreme, classical approaches provide orders of magnitude faster simulations; however they regard chemical bonds as immutable entities. A few exceptions exist, but these are not always trivial to adopt for routine use. We bridge this gap by providing a novel, pseudo-classical approach, based on explicit valency. We unpack molecules into valence electron pairs and atomic cores. Particles bear ionic charges and interact via pairwise-only potentials. The potentials are informed of quantum effects in the short-range and obey dissociation limits in the long-range. They are trained against a small set of isolated species, including geometries and thermodynamics of small hydrides and of dimers formed by them. The resulting force field captures the essentials of reactivity, polarizability and flexibility in a simple, seamless setting. We call this model LEWIS, after the chemical theory that inspired the use of valence pairs. Following the introduction in Chapter 1, we initially focus on the properties of water. Chapter 2 considers gas phase clusters. To transition to the liquid phase, Chapter 3 describes a novel pairwise long-range compensation that performs comparably to infinite lattice summations. The approach is suited to ionic solutions in general. In Chapters 4 and 5, LEWIS is shown to correctly predict the dipolar and quadrupolar response in bulk liquid, and can accommodate proton transfers in both acid and base. Efficiency permits the study of proton defects at dilutions not accessible to experiment or quantum mechanics. Chapter 6 discusses explicit valency approaches in other hydrides, forming the basis of a reactive organic force field. Examples of simple

  2. Development of explicit criteria for cholecystectomy

    PubMed Central

    Quintana, J; Cabriada, J; d Lopez; Varona, M; Oribe, V; Barrios, B; Arostegui, I; Bilbao, A

    2002-01-01

    Objective: Consensus development techniques were used in the late 1980s to create explicit criteria for the appropriateness of cholecystectomy. New diagnostic and treatment techniques have been developed in the last decade, so an updated appropriateness of indications tool was developed for cholecystectomy in patients with non-malignant diseases. The validity and reliability of panel results using this tool were tested. Methods: Criteria were developed using a modified Delphi panel judgement process. The level of agreement between the panellists (six gastroenterologists and six surgeons) was analysed and the ratings were compared with those of a second different panel using weighted kappa statistics. Results: The results of the main panel were presented as a decision tree. Of the 210 scenarios evaluated by the main panel in the second round, 51% were found appropriate, 26% uncertain, and 23% inappropriate. Agreement was achieved in 54% of the scenarios and disagreement in 3%. Although the gastroenterologists tended to score fewer scenarios as appropriate, as a group they did not differ from the surgeons. Comparison of the ratings of the main panel with those of a second panel resulted in a weighted kappa statistic of 0.75. Conclusions: The parameters tested showed acceptable validity and reliability results for an evaluation tool. These results support the use of this algorithm as a screening tool for assessing the appropriateness of cholecystectomy. PMID:12468691

  3. Modeling of solvent flow effects in enzyme catalysis under physiological conditions

    NASA Astrophysics Data System (ADS)

    Schofield, Jeremy; Inder, Paul; Kapral, Raymond

    2012-05-01

    A stochastic model for the dynamics of enzymatic catalysis in explicit, effective solvents under physiological conditions is presented. Analytically-computed first passage time densities of a diffusing particle in a spherical shell with absorbing boundaries are combined with densities obtained from explicit simulation to obtain the overall probability density for the total reaction cycle time of the enzymatic system. The method is used to investigate the catalytic transfer of a phosphoryl group in a phosphoglycerate kinase-ADP-bis phosphoglycerate system, one of the steps of glycolysis. The direct simulation of the enzyme-substrate binding and reaction is carried out using an elastic network model for the protein, and the solvent motions are described by multiparticle collision dynamics which incorporates hydrodynamic flow effects. Systems where solvent-enzyme coupling occurs through explicit intermolecular interactions, as well as systems where this coupling is taken into account by including the protein and substrate in the multiparticle collision step, are investigated and compared with simulations where hydrodynamic coupling is absent. It is demonstrated that the flow of solvent particles around the enzyme facilitates the large-scale hinge motion of the enzyme with bound substrates, and has a significant impact on the shape of the probability densities and average time scales of substrate binding for substrates near the enzyme, the closure of the enzyme after binding, and the overall time of completion of the cycle.

  4. Solvent/Non-Solvent Sintering To Make Microsphere Scaffolds

    NASA Technical Reports Server (NTRS)

    Laurencin, Cato T.; Brown, Justin L.; Nair, Lakshmi

    2011-01-01

    A solvent/non-solvent sintering technique has been devised for joining polymeric microspheres to make porous matrices for use as drug-delivery devices or scaffolds that could be seeded with cells for growing tissues. Unlike traditional sintering at elevated temperature and pressure, this technique is practiced at room temperature and pressure and, therefore, does not cause thermal degradation of any drug, protein, or other biochemical with which the microspheres might be loaded to impart properties desired in a specific application. Also, properties of scaffolds made by this technique are more reproducible than are properties of comparable scaffolds made by traditional sintering. The technique involves the use of two miscible organic liquids: one that is and one that is not a solvent for the affected polymer. The polymeric microspheres are placed in a mold having the size and shape of the desired scaffold, then the solvent/non-solvent mixture is poured into the mold to fill the void volume between the microspheres, then the liquid mixture is allowed to evaporate. Some of the properties of the resulting scaffold can be tailored through choice of the proportions of the liquids and the diameter of the microspheres.

  5. Computational comparison of oxidation stability: Solvent/salt monomers vs solvent-solvent/salt pairs

    NASA Astrophysics Data System (ADS)

    Kim, Dong Young; Park, Min Sik; Lim, Younhee; Kang, Yoon-Sok; Park, Jin-Hwan; Doo, Seok-Gwang

    2015-08-01

    A fundamental understanding of the anodic stabilities of electrolytes is important for the development of advanced high-voltage electrolytes. In this study, we calculated and systematically compared the oxidation stabilities of monomeric solvents and anions, and bimolecular solvent-solvent and anion-solvent systems that are considered to be high-voltage electrolyte components, using ab initio calculations. Oxidation stabilities of solvent or anion monomers without considering specific solvation molecules cannot represent experimental oxidation stabilities. The oxidation of electrolytes usually forms neutral or cationic radicals, which immediately undergo further reactions stabilizing the products. Oxidatively driven intermolecular reactions are the main reason for the lower oxidation stabilities of electrolytes compared with those of monomeric compounds. Electrolyte components such as tetramethylene sulfone (TMS), ethyl methyl sulfone (EMS), bis(oxalate)borate (BOB-), and bis(trifluoromethane)sulfonamide (TFSI-) that minimize such intermolecular chemical reactions on oxidation can maintain the oxidation stabilities of monomers. In predictions of the theoretical oxidation stabilities of electrolytes, simple comparisons of highest occupied molecular orbital energies can be misleading, even if microsolvation or bulk clusters are considered. Instead, bimolecular solvent complexes with a salt anion should be at least considered in oxidation calculations. This study provides important information on fundamental and applied aspects of the development of electrolytes.

  6. Quantification of Solvent Contribution to the Stability of Noncovalent Complexes.

    PubMed

    Zhang, Haiyang; Tan, Tianwei; Hetényi, Csaba; van der Spoel, David

    2013-10-08

    We introduce an indirect approach to estimate the solvation contributions to the thermodynamics of noncovalent complex formation through molecular dynamics simulation. This estimation is demonstrated by potential of mean force and entropy calculations on the binding process between β-cyclodextrin (host) and four drug molecules puerarin, daidzin, daidzein, and nabumetone (guest) in explicit water, followed by a stepwise extraction of individual enthalpy (ΔH) and entropy (ΔS) terms from the total free energy. Detailed analysis on the energetics of the host-guest complexation demonstrates that flexibility of the binding partners and solvation-related ΔH and ΔS need to be included explicitly for accurate estimation of the binding thermodynamics. From this, and our previous work on the solvent dependency of binding energies (Zhang et al. J. Phys. Chem. B 2012, 116, 12684-12693), it follows that calculations neglecting host or guest flexibility, or those employing implicit solvent, will not be able to systematically predict binding free energies. The approach presented here can be readily adopted for obtaining a deeper understanding of the mechanisms governing noncovalent associations in solution.

  7. Spatially explicit modeling in ecology: A review

    USGS Publications Warehouse

    DeAngelis, Donald L.; Yurek, Simeon

    2017-01-01

    The use of spatially explicit models (SEMs) in ecology has grown enormously in the past two decades. One major advancement has been that fine-scale details of landscapes, and of spatially dependent biological processes, such as dispersal and invasion, can now be simulated with great precision, due to improvements in computer technology. Many areas of modeling have shifted toward a focus on capturing these fine-scale details, to improve mechanistic understanding of ecosystems. However, spatially implicit models (SIMs) have played a dominant role in ecology, and arguments have been made that SIMs, which account for the effects of space without specifying spatial positions, have an advantage of being simpler and more broadly applicable, perhaps contributing more to understanding. We address this debate by comparing SEMs and SIMs in examples from the past few decades of modeling research. We argue that, although SIMs have been the dominant approach in the incorporation of space in theoretical ecology, SEMs have unique advantages for addressing pragmatic questions concerning species populations or communities in specific places, because local conditions, such as spatial heterogeneities, organism behaviors, and other contingencies, produce dynamics and patterns that usually cannot be incorporated into simpler SIMs. SEMs are also able to describe mechanisms at the local scale that can create amplifying positive feedbacks at that scale, creating emergent patterns at larger scales, and therefore are important to basic ecological theory. We review the use of SEMs at the level of populations, interacting populations, food webs, and ecosystems and argue that SEMs are not only essential in pragmatic issues, but must play a role in the understanding of causal relationships on landscapes.

  8. Coal liquefaction process with enhanced process solvent

    DOEpatents

    Givens, Edwin N.; Kang, Dohee

    1984-01-01

    In an improved coal liquefaction process, including a critical solvent deashing stage, high value product recovery is improved and enhanced process-derived solvent is provided by recycling second separator underflow in the critical solvent deashing stage to the coal slurry mix, for inclusion in the process solvent pool.

  9. Solvent electronic polarization effects on a charge transfer excitation studied by the mean-field QM/MM method

    SciTech Connect

    Nakano, Hiroshi

    2015-12-31

    Electronic polarization effects of a medium can have a significant impact on a chemical reaction in condensed phases. We discuss the effects on the charge transfer excitation of a chromophore, N,N-dimethyl-4-nitroaniline, in various solvents using the mean-field QM/MM method with a polarizable force field. The results show that the explicit consideration of the solvent electronic polarization effects is important especially for a solvent with a low dielectric constant when we study the solvatochromism of the chromophore.

  10. Method of treating radioactively contaminated solvent waste

    SciTech Connect

    Jablonski, W.; Mallek, H.; Plum, W.

    1981-07-07

    A method of and apparatus for treating radioactively contaminated solvent waste are claimed. The solvent waste is supplied to material such as peat, vermiculite, diaton, etc. This material effects the distribution or dispersion of the solvent and absorbs the foreign substances found in the solvent waste. Air or an inert gas flows through the material in order to pick up the solvent portions which are volatile as a consequence of their vapor pressure. The thus formed gas mixture, which includes air or inert gas and solvent portions, is purified in a known manner by thermal, electrical, or catalytic combustion of the solvent portions.

  11. Acid Base Titrations in Nonaqueous Solvents and Solvent Mixtures

    NASA Astrophysics Data System (ADS)

    Barcza, Lajos; Buvári-Barcza, Ágnes

    2003-07-01

    The acid base determination of different substances by nonaqueous titrations is highly preferred in pharmaceutical analyses since the method is quantitative, exact, and reproducible. The modern interpretation of the reactions in nonaqueous solvents started in the last century, but several inconsistencies and unsolved problems can be found in the literature. The acid base theories of Brønsted Lowry and Lewis as well as the so-called solvent theory are outlined first, then the promoting (and leveling) and the differentiating effects are discussed on the basis of the hydrogen-bond concept. Emphasis is put on the properties of formic acid and acetic anhydride since their importance is increasing.

  12. DOE solvent handbook information sheet

    SciTech Connect

    Chavez, A.A.

    1992-01-01

    Solvents and cleaners are used in the Department of Defense (DOD) and the Department of Energy-Defense Program (DOE-DP) maintenance facilities for removing wax, grease, oil, carbon, machining fluids, solder fluxes, mold releases, and other contaminants before repairing or electroplating parts. Private industry also uses cleaners and degreasers for surface preparation of various metals. Growing environmental and worker safety concerns have brought attention to these solvents and cleaners, most of which are classified as toxic. Tightening government regulations have already excluded the use of some chemicals, and restrict the use of various halogenated hydrocarbons because of their atmospheric-ozone depleting effects, as well as their cancer-related risks. As a result, a program was established to develop an efficient, easily accessible, electronic solvent utilization handbook. This is being accomplished by: (1) identifying solvents (alternatives) that are not currently restricted by government regulations for use DOE-DP facilities, and private industry, (2) evaluating their cleaning performance, (3) evaluating their corrosivity, (4) evaluating their air emissions, (5) evaluating the possibility of recycling or recovering all or portions of the alternative degreasers, (6) testing substitute solvents compatibility with non-metallic materials, (7) inputting all of the data gathered (including previous biodegradability information) into a database, and (8) developing a methodology for efficient, widespread access to the data base information system.

  13. DOE solvent handbook information sheet

    SciTech Connect

    Chavez, A.A.

    1992-05-01

    Solvents and cleaners are used in the Department of Defense (DOD) and the Department of Energy-Defense Program (DOE-DP) maintenance facilities for removing wax, grease, oil, carbon, machining fluids, solder fluxes, mold releases, and other contaminants before repairing or electroplating parts. Private industry also uses cleaners and degreasers for surface preparation of various metals. Growing environmental and worker safety concerns have brought attention to these solvents and cleaners, most of which are classified as toxic. Tightening government regulations have already excluded the use of some chemicals, and restrict the use of various halogenated hydrocarbons because of their atmospheric-ozone depleting effects, as well as their cancer-related risks. As a result, a program was established to develop an efficient, easily accessible, electronic solvent utilization handbook. This is being accomplished by: (1) identifying solvents (alternatives) that are not currently restricted by government regulations for use DOE-DP facilities, and private industry, (2) evaluating their cleaning performance, (3) evaluating their corrosivity, (4) evaluating their air emissions, (5) evaluating the possibility of recycling or recovering all or portions of the alternative degreasers, (6) testing substitute solvents compatibility with non-metallic materials, (7) inputting all of the data gathered (including previous biodegradability information) into a database, and (8) developing a methodology for efficient, widespread access to the data base information system.

  14. A solvent model for simulations of peptides in bilayers. II. Membrane-spanning alpha-helices.

    PubMed Central

    Efremov, R G; Nolde, D E; Vergoten, G; Arseniev, A S

    1999-01-01

    We describe application of the implicit solvation model (see the first paper of this series), to Monte Carlo simulations of several peptides in bilayer- and water-mimetic environments, and in vacuum. The membrane-bound peptides chosen were transmembrane segments A and B of bacteriorhodopsin, the hydrophobic segment of surfactant lipoprotein, and magainin2. Their conformations in membrane-like media are known from the experiments. Also, molecular dynamics study of surfactant lipoprotein with different explicit solvents has been reported (Kovacs, H., A. E. Mark, J. Johansson, and W. F. van Gunsteren. 1995. J. Mol. Biol. 247:808-822). The principal goal of this work is to compare the results obtained in the framework of our solvation model with available experimental and computational data. The findings could be summarized as follows: 1) structural and energetic properties of studied molecules strongly depend on the solvent; membrane-mimetic media significantly promote formation of alpha-helices capable of traversing the bilayer, whereas a polar environment destabilizes alpha-helical conformation via reduction of solvent-exposed surface area and packing; 2) the structures calculated in a membrane-like environment agree with the experimental ones; 3) noticeable differences in conformation of surfactant lipoprotein assessed via Monte Carlo simulation with implicit solvent (this work) and molecular dynamics in explicit solvent were observed; 4) in vacuo simulations do not correctly reproduce protein-membrane interactions, and hence should be avoided in modeling membrane proteins. PMID:10233063

  15. Helpful hints for physical solvent absorption

    SciTech Connect

    Wolfer, W.

    1982-11-01

    Review of experience with natural gas treatment using physical solvents points to design and operating suggestions. Experiences with three plants using either Selexol or Sepasolv MPE solvent shows that both solvents perform well. The solvents offer economical and problem-free purification of natural gas. The Sepasolv MPE and Selexol solvents are very similar in chemical structure and physical properties. Thus, their application range is almost similar. An exchange is possible in most plants without equipment modification and/or process data.

  16. Solvent-regenerated activated carbon

    SciTech Connect

    McLaughlin, H. )

    1988-07-01

    This report summarizes the results of a University/Industry research project, sponsored by the New York State Energy Research and Development Authority and Fluids Design Corporation. The research project studied the solvent regeneration of activated carbon. Activate carbon was used to remove trace organics from aqueous streams, then regenerated by desorbing the adsorbates with organic solvents. The project included a survey of the potential applications in New York State industries, fundamental research on the adsorption/desorption phenomena, and design of a full-scale process. The economics of the full-scale process were evaluated and compared to alternate available technologies. The result of this work is a versatile process with attractive economics. A wide range of adsorbates and solvents were found to be acceptable for this process. The design methodologies are developed and the techniques for evaluating a new application are delineated. 13 refs., 12 figs., 4 tabs.

  17. Coil-globule transition of macromolecules in mixed solvent: A semi-grand canonical molecular dynamics approach

    NASA Astrophysics Data System (ADS)

    Mukherji, Debashish; Kremer, Kurt

    2014-03-01

    Conformational transition of macromolecules in mixed solvents are intimately linked to large local concentration fluctuations of solvent components. The numerical studies in the field are limited to the closed boundary schemes, which, however, suffer from severe system size effects. To overcome this discrepancy, we have developed a semi-grand canonical molecular dynamics scheme for complex fluids. Our method makes use of the adaptive resolution scheme (AdResS) with a metropolis particle exchange criterion. In AdResS, an all-atom region, containing macromolecule, is coupled to a coarse-grained (CG) reservoir. The semi-grand canonical particle exchange is performed in the CG region. As the applications of the method, we study the concentration driven reentrant collapse and swelling transition of poly(N-isopropylacrylamide) (PNIPAm) and poly(N,N-diethylacrylamide) (PDEAm) in aqueous methanol and demonstrate the role of the delicate interplay of the different intermolecular interactions.

  18. Solvent reorganization of electron transitions in viscous solvents

    SciTech Connect

    Ghorai, Pradip K.; Matyushov, Dmitry V.

    2006-04-14

    We develop a model of electron transfer reactions at conditions of nonergodicity when the time of solvent relaxation crosses the observation time window set up by the reaction rate. Solvent reorganization energy of intramolecular electron transfer in a charge-transfer molecule dissolved in water and acetonitrile is studied by molecular dynamics simulations at varying temperatures. We observe a sharp decrease of the reorganization energy at a temperature identified as the temperature of structural arrest due to cage effect, as discussed by the mode-coupling theory. This temperature also marks the onset of the enhancement of translational diffusion relative to rotational relaxation signaling the breakdown of the Stokes-Einstein relation. The change in the reorganization energy at the transition temperature reflects the dynamical arrest of the slow, collective relaxation of the solvent related to the relaxation of the solvent dipolar polarization. An analytical theory proposed to describe this effect agrees well with both the simulations and experimental Stokes shift data. The theory is applied to the analysis of charge-transfer kinetics in a low-temperature glass former. We show that the reorganization energy is substantially lower than its equilibrium value for the low-temperature portion of the data. The theory predicts the possibility of discontinuous changes in the dependence of the electron transfer rate on the free energy gap when the reaction switches between ergodic and nonergodic regimes.

  19. Dielectric anisotropy in polar solvents under external fields

    NASA Astrophysics Data System (ADS)

    Buyukdagli, Sahin

    2015-08-01

    We investigate dielectric saturation and increment in polar liquids under external fields. We couple a previously introduced dipolar solvent model to a uniform electric field and derive the electrostatic kernel of interacting dipoles. This procedure allows an unambiguous definition of the liquid dielectric permittivity embodying non-linear dielectric response and correlation effects. We find that the presence of the external field results in a dielectric anisotropy characterized by a two-component dielectric permittivity tensor. The increase of the electric field amplifies the permittivity component parallel to the field direction, i.e. dielectric increment is observed along the field. However, the perpendicular component is lowered below the physiological permittivity {{\\varepsilon}w}≈ 77 , indicating dielectric saturation perpendicular to the field. By comparison with Molecular Dynamics simulations from the literature, we show that the mean-field level dielectric response theory underestimates dielectric saturation. The inclusion of dipolar correlations at the weak-coupling level intensify the mean-field level dielectric saturation and improves the agreement with simulation data at weak electric fields. The correlation-corrected theory predicts as well the presence of a metastable configuration corresponding to the antiparallel alignment of dipoles with the field. This prediction can be verified by solvent-explicit simulations where solvent molecules are expected to be trapped transiently in this metastable state.

  20. Effects of Explicit Instructions, Metacognition, and Motivation on Creative Performance

    ERIC Educational Resources Information Center

    Hong, Eunsook; O'Neil, Harold F.; Peng, Yun

    2016-01-01

    Effects of explicit instructions, metacognition, and intrinsic motivation on creative homework performance were examined in 303 Chinese 10th-grade students. Models that represent hypothesized relations among these constructs and trait covariates were tested using structural equation modelling. Explicit instructions geared to originality were…

  1. "Make It Explicit!": Improving Collaboration through Increase of Script Coercion

    ERIC Educational Resources Information Center

    Papadopoulos, P. M.; Demetriadis, S. N.; Weinberger, A.

    2013-01-01

    This paper investigates the impact of the proposed "Make It Explicit!" technique on students' learning when participating in scripted collaborative activities. The method posits that when asking students to proactively articulate their own positions explicitly, then improved peer interaction is triggered in a subsequent…

  2. Measuring Explicit and Implicit Knowledge: A Psychometric Study in SLA

    ERIC Educational Resources Information Center

    Ebadi, Mandana Rohollahzadeh; Abedalaziz, Nabeel; Saad, Mohd Rashid Mohd

    2015-01-01

    Lack of valid means of measuring explicit and implicit knowledge in acquisition of second language is a concern issue in investigations of explicit and implicit learning. This paper endeavors to validate the use of four tests (i.e., Untimed Judgment Grammatical Test, UJGT; Test of Metalinguistic Knowledge, TMK; Elicited Oral Imitation Test, EOIT;…

  3. Explicit Knowledge and Learning in SLA: A Cognitive Linguistics Perspective

    ERIC Educational Resources Information Center

    Roehr, Karen

    2010-01-01

    SLA researchers agree that explicit knowledge and learning play an important role in adult L2 development. In the field of cognitive linguistics, it has been proposed that implicit and explicit knowledge differ in terms of their internal category structure and the processing mechanisms that operate on their representation in the human mind. It has…

  4. The Ms. Stereotype Revisited: Implicit and Explicit Facets

    ERIC Educational Resources Information Center

    Malcolmson, Kelly A.; Sinclair, Lisa

    2007-01-01

    Implicit and explicit stereotypes toward the title Ms. were examined. Participants read a short description of a target person whose title of address varied (Ms., Mrs., Miss, Mr.). They then rated the person on agentic and communal traits and completed an Implicit Association Test. Replicating earlier research (Dion, 1987), at an explicit level,…

  5. Functional differences between statistical learning with and without explicit training

    PubMed Central

    Reber, Paul J.; Paller, Ken A.

    2015-01-01

    Humans are capable of rapidly extracting regularities from environmental input, a process known as statistical learning. This type of learning typically occurs automatically, through passive exposure to environmental input. The presumed function of statistical learning is to optimize processing, allowing the brain to more accurately predict and prepare for incoming input. In this study, we ask whether the function of statistical learning may be enhanced through supplementary explicit training, in which underlying regularities are explicitly taught rather than simply abstracted through exposure. Learners were randomly assigned either to an explicit group or an implicit group. All learners were exposed to a continuous stream of repeating nonsense words. Prior to this implicit training, learners in the explicit group received supplementary explicit training on the nonsense words. Statistical learning was assessed through a speeded reaction-time (RT) task, which measured the extent to which learners used acquired statistical knowledge to optimize online processing. Both RTs and brain potentials revealed significant differences in online processing as a function of training condition. RTs showed a crossover interaction; responses in the explicit group were faster to predictable targets and marginally slower to less predictable targets relative to responses in the implicit group. P300 potentials to predictable targets were larger in the explicit group than in the implicit group, suggesting greater recruitment of controlled, effortful processes. Taken together, these results suggest that information abstracted through passive exposure during statistical learning may be processed more automatically and with less effort than information that is acquired explicitly. PMID:26472644

  6. Organic Solvent Effects in Biomass Conversion Reactions.

    PubMed

    Shuai, Li; Luterbacher, Jeremy

    2016-01-01

    Transforming lignocellulosic biomass into fuels and chemicals has been intensely studied in recent years. A large amount of work has been dedicated to finding suitable solvent systems, which can improve the transformation of biomass into value-added chemicals. These efforts have been undertaken based on numerous research results that have shown that organic solvents can improve both conversion and selectivity of biomass to platform molecules. We present an overview of these organic solvent effects, which are harnessed in biomass conversion processes, including conversion of biomass to sugars, conversion of sugars to furanic compounds, and production of lignin monomers. A special emphasis is placed on comparing the solvent effects on conversion and product selectivity in water with those in organic solvents while discussing the origins of the differences that arise. We have categorized results as benefiting from two major types of effects: solvent effects on solubility of biomass components including cellulose and lignin and solvent effects on chemical thermodynamics including those affecting reactants, intermediates, products, and/or catalysts. Finally, the challenges of using organic solvents in industrial processes are discussed from the perspective of solvent cost, solvent stability, and solvent safety. We suggest that a holistic view of solvent effects, the mechanistic elucidation of these effects, and the careful consideration of the challenges associated with solvent use could assist researchers in choosing and designing improved solvent systems for targeted biomass conversion processes.

  7. Risk assessment for halogenated solvents

    SciTech Connect

    Travis, C.C.

    1988-01-01

    A recent development in the cancer risk area is the advent of biologically based pharmacokinetic and pharmacodynamic models. These models allow for the incorporation of biological and mechanistic data into the risk assessment process. These advances will not only improve the risk assessment process for halogenated solvents but will stimulate and guide basic research in the biological area.

  8. A semi-implicit solvent model for the simulation of peptides and proteins.

    PubMed

    Basdevant, Nathalie; Borgis, Daniel; Ha-Duong, Tap

    2004-06-01

    We present a new model of biomolecules hydration based on macroscopic electrostatic theory, that can both describe the microscopic details of solvent-solute interactions and allow for an efficient evaluation of the electrostatic hydration free energy. This semi-implicit model considers the solvent as an ensemble of polarizable pseudoparticles whose induced dipole describe both the electronic and orientational solvent polarization. In the presented version of the model, there is no mutual dipolar interaction between the particles, and they only interact through short-ranged Lennard-Jones interactions. The model has been integrated into a molecular dynamics code, and offers the possibility to simulate efficiently the conformational evolution of biomolecules. It is able to provide estimations of the electrostatic solvation free energy within short time windows during the simulation. It has been applied to the study of two small peptides, the octaalanine and the N-terminal helix of ribonuclease A, and two proteins, the bovine pancreatic trypsin inhibitor and the B1 immunoglobin-binding domain of streptococcal protein G. Molecular dynamics simulations of these biomolecules, using a slightly modified Amber force field, provide stable and meaningful trajectories in overall agreement with experiments and all-atom simulations. Correlations with respect to Poisson-Boltzmann electrostatic solvation free energies are also presented to discuss the parameterization of the model and its consequences.

  9. Replacement solvents for use in chemical synthesis

    DOEpatents

    Molnar, Linda K.; Hatton, T. Alan; Buchwald, Stephen L.

    2001-05-15

    Replacement solvents for use in chemical synthesis include polymer-immobilized solvents having a flexible polymer backbone and a plurality of pendant groups attached onto the polymer backbone, the pendant groups comprising a flexible linking unit bound to the polymer backbone and to a terminal solvating moiety. The polymer-immobilized solvent may be dissolved in a benign medium. Replacement solvents for chemical reactions for which tetrahydrofuran or diethyl may be a solvent include substituted tetrahydrofurfuryl ethers and substituted tetrahydro-3-furan ethers. The replacement solvents may be readily recovered from the reaction train using conventional methods.

  10. Theoretical study of the solvent effect on the aromaticity of benzene: a NICS analysis.

    PubMed

    Junqueira, Georgia M A; Dos Santos, Hélio F

    2014-03-01

    Nucleus-independent chemical shift (NICS) quantities for benzene-benzene and benzene-water species were obtained and are discussed in gas phase and in solution. Besides standard polarizable continuum model (PCM) calculations, sequential Monte Carlo/quantum mechanics (S-MC/QM) were also performed. Benzene was shown to be slightly more aromatic in condensate phase when we considered the average solvent configuration (ASEC) approach with explicit molecules.

  11. Probing the role of interfacial waters in protein-DNA recognition using a hybrid implicit/explicit solvation model.

    PubMed

    Li, Shen; Bradley, Philip

    2013-08-01

    When proteins bind to their DNA target sites, ordered water molecules are often present at the protein-DNA interface bridging protein and DNA through hydrogen bonds. What is the role of these ordered interfacial waters? Are they important determinants of the specificity of DNA sequence recognition, or do they act in binding in a primarily nonspecific manner, by improving packing of the interface, shielding unfavorable electrostatic interactions, and solvating unsatisfied polar groups that are inaccessible to bulk solvent? When modeling details of structure and binding preferences, can fully implicit solvent models be fruitfully applied to protein-DNA interfaces, or must the individualistic properties of these interfacial waters be accounted for? To address these questions, we have developed a hybrid implicit/explicit solvation model that specifically accounts for the locations and orientations of small numbers of DNA-bound water molecules, while treating the majority of the solvent implicitly. Comparing the performance of this model with that of its fully implicit counterpart, we find that explicit treatment of interfacial waters results in a modest but significant improvement in protein side-chain placement and DNA sequence recovery. Base-by-base comparison of the performance of the two models highlights DNA sequence positions whose recognition may be dependent on interfacial water. Our study offers large-scale statistical evidence for the role of ordered water for protein-DNA recognition, together with detailed examination of several well-characterized systems. In addition, our approach provides a template for modeling explicit water molecules at interfaces that should be extensible to other systems.

  12. The effect of explicit financial incentives on physician behavior.

    PubMed

    Armour, B S; Pitts, M M; Maclean, R; Cangialose, C; Kishel, M; Imai, H; Etchason, J

    2001-05-28

    Managed care organizations use explicit financial incentives to influence physicians' use of resources. This has contributed to concerns regarding conflicts of interest for physicians and adverse effects on the quality of patient care. In light of recent publicized legislative and legal battles about this issue, we reviewed the literature and analyzed studies that examine the effect of these explicit financial incentives on the behavior of physicians. The method used to undertake the literature review followed the approach set forth in the Cochrane Collaboration handbook. Our literature review revealed a paucity of data on the effect of explicit financial incentives. Based on this limited evidence, explicit incentives that place individual physicians at financial risk appear to be effective in reducing physician resource use. However, the empirical evidence regarding the effectiveness of bonus payments on physician resource use is mixed. Similarly, our review revealed mixed effects of the influence of explicit financial incentives on the quality of patient care. The effect of explicit financial incentives on physician behavior is complicated by a lack of understanding of the incentive structure by the managed care organization and the physician. The lack of a universally acceptable definition of quality renders it important that future researchers identify the term explicitly.

  13. Transformation between α-helix and β-sheet structures of one and two polyglutamine peptides in explicit water molecules by replica-exchange molecular dynamics simulations.

    PubMed

    Chiang, Hsin-Lin; Chen, Chun-Jung; Okumura, Hisashi; Hu, Chin-Kun

    2014-07-15

    Aggregation of polyglutamine peptides with β-sheet structures is related to some important neurodegenerative diseases such as Huntington's disease. However, it is not clear how polyglutamine peptides form the β-sheets and aggregate. To understand this problem, we performed all-atom replica-exchange molecular dynamics simulations of one and two polyglutamine peptides with 10 glutamine residues in explicit water molecules. Our results show that two polyglutamine peptides mainly formed helix or coil structures when they are separated, as in the system with one-polyglutamine peptide. As the interpeptide distance decreases, the intrapeptide β-sheet structure sometimes appear as an intermediate state, and finally the interpeptide β-sheets are formed. We also find that the polyglutamine dimer tends to form the antiparallel β-sheet conformations rather than the parallel β-sheet, which is consistent with previous experiments and a coarse-grained molecular dynamics simulation.

  14. Disentangling Rheumatoid Arthritis Patients’ Implicit and Explicit Attitudes toward Methotrexate

    PubMed Central

    Linn, Annemiek J.; Vandeberg, Lisa; Wennekers, Annemarie M.; Vervloet, Marcia; van Dijk, Liset; van den Bemt, Bart J. F.

    2016-01-01

    Medication non-adherence is a major public health problem that has been termed an ‘invisible epidemic.’ Non-adherence is not only associated with negative clinical consequences but can also result in substantial healthcare costs. Up to now, effective adherence interventions are scarce and a more comprehensive model of adherence determinants is required to target the determinants for not taking the medication as prescribed. Current approaches only included explicit attitudes such as self-reported evaluations of medication as determinants, neglecting the role of associative processes that shape implicit attitudes. Implicit processes can predict daily behavior more accurately than explicit attitudes. Our aim is to assess explicit and implicit attitudes toward medication and explore the relation with beliefs, adherence and clinical (laboratory) outcomes in chronically ill patients. Fifty two Rheumatic Arthritis (RA) patients’ attitudes toward Methotrexate (MTX) were explicitly (self-reported) and implicitly (Single-Category Implicit Association Test) assessed and related to the Beliefs about Medicine Questionnaire, the Compliance Questionnaire on Rheumatology and laboratory parameters [Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP)]. Results show that explicit attitudes were positive and health-related. Implicit attitudes were, however, negative and sickness-related. Half of the patients displayed explicitly positive but implicitly negative attitudes. Explicit attitudes were positively related to ESR. A positive relationship between implicit attitudes and disease duration was observed. In this study, we have obtained evidence suggesting that the measurement of implicit attitudes and associations provides different information than explicit, self-reported attitudes toward medication. Since patients’ implicit attitudes deviated from explicit attitudes, we can conclude that the relationship between implicit attitudes and medication adherence is

  15. Charged patchy particle models in explicit salt: Ion distributions, electrostatic potentials, and effective interactions

    SciTech Connect

    Yigit, Cemil; Dzubiella, Joachim; Heyda, Jan

    2015-08-14

    We introduce a set of charged patchy particle models (CPPMs) in order to systematically study the influence of electrostatic charge patchiness and multipolarity on macromolecular interactions by means of implicit-solvent, explicit-ion Langevin dynamics simulations employing the Gromacs software. We consider well-defined zero-, one-, and two-patched spherical globules each of the same net charge and (nanometer) size which are composed of discrete atoms. The studied mono- and multipole moments of the CPPMs are comparable to those of globular proteins with similar size. We first characterize ion distributions and electrostatic potentials around a single CPPM. Although angle-resolved radial distribution functions reveal the expected local accumulation and depletion of counter- and co-ions around the patches, respectively, the orientation-averaged electrostatic potential shows only a small variation among the various CPPMs due to space charge cancellations. Furthermore, we study the orientation-averaged potential of mean force (PMF), the number of accumulated ions on the patches, as well as the CPPM orientations along the center-to-center distance of a pair of CPPMs. We compare the PMFs to the classical Derjaguin-Verwey-Landau-Overbeek theory and previously introduced orientation-averaged Debye-Hückel pair potentials including dipolar interactions. Our simulations confirm the adequacy of the theories in their respective regimes of validity, while low salt concentrations and large multipolar interactions remain a challenge for tractable theoretical descriptions.

  16. Rational Design of Particle Mesh Ewald Compatible Lennard-Jones Parameters for +2 Metal Cations in Explicit Solvent.

    PubMed

    Li, Pengfei; Roberts, Benjamin P; Chakravorty, Dhruva K; Merz, Kenneth M

    2013-06-11

    Metal ions play significant roles in biological systems. Accurate molecular dynamics (MD) simulations on these systems require a validated set of parameters. Although there are more detailed ways to model metal ions, the nonbonded model, which employs a 12-6 Lennard-Jones (LJ) term plus an electrostatic potential is still widely used in MD simulations today due to its simple form. However, LJ parameters have limited transferability due to different combining rules, various water models and diverse simulation methods. Recently, simulations employing a Particle Mesh Ewald (PME) treatment for long-range electrostatics have become more and more popular owing to their speed and accuracy. In the present work we have systematically designed LJ parameters for 24 +2 metal (M(II)) cations to reproduce different experimental properties appropriate for the Lorentz-Berthelot combining rules and PME simulations. We began by testing the transferability of currently available M(II) ion LJ parameters. The results showed that there are differences between simulations employing Ewald summation with other simulation methods and that it was necessary to design new parameters specific for PME based simulations. Employing the thermodynamic integration (TI) method and performing periodic boundary MD simulations employing PME, allowed for the systematic investigation of the LJ parameter space. Hydration free energies (HFEs), the ion-oxygen distance in the first solvation shell (IOD) and coordination numbers (CNs) were obtained for various combinations of the parameters of the LJ potential for four widely used water models (TIP3P, SPC/E, TIP4P and TIP4PEW). Results showed that the three simulated properties were highly correlated. Meanwhile, M(II) ions with the same parameters in different water models produce remarkably different HFEs but similar structural properties. It is difficult to reproduce various experimental values simultaneously because the nonbonded model underestimates the interaction between the metal ions and water molecules at short range. Moreover, the extent of underestimation increases successively for the TIP3P, SPC/E, TIP4PEW and TIP4P water models. Nonetheless, we fitted a curve to describe the relationship between ε (the well depth) and radius (Rmin/2) from experimental data on noble gases to facilitate the generation of the best possible compromise models. Hence, by targeting different experimental values, we developed three sets of parameters for M(II) cations for three different water models (TIP3P, SPC/E and TIP4PEW). These parameters we feel represent the best possible compromise that can be achieved using the nonbonded model for the ions in combination with simple water models. From a computational uncertainty analysis we estimate that the uncertainty in our computed HFEs is on the order of ±1kcal/mol. Further improvements will require more advanced non-bonded models likely with inclusion of polarization.

  17. Hierarchical structure of the energy landscape of proteins revisited by time series analysis. II. Investigation of explicit solvent effects

    NASA Astrophysics Data System (ADS)

    Alakent, Burak; Camurdan, Mehmet C.; Doruker, Pemra

    2005-10-01

    Time series analysis tools are employed on the principal modes obtained from the Cα trajectories from two independent molecular-dynamics simulations of α-amylase inhibitor (tendamistat). Fluctuations inside an energy minimum (intraminimum motions), transitions between minima (interminimum motions), and relaxations in different hierarchical energy levels are investigated and compared with those encountered in vacuum by using different sampling window sizes and intervals. The low-frequency low-indexed mode relationship, established in vacuum, is also encountered in water, which shows the reliability of the important dynamics information offered by principal components analysis in water. It has been shown that examining a short data collection period (100ps) may result in a high population of overdamped modes, while some of the low-frequency oscillations (<10cm-1) can be captured in water by using a longer data collection period (1200ps). Simultaneous analysis of short and long sampling window sizes gives the following picture of the effect of water on protein dynamics. Water makes the protein lose its memory: future conformations are less dependent on previous conformations due to the lowering of energy barriers in hierarchical levels of the energy landscape. In short-time dynamics (<10ps), damping factors extracted from time series model parameters are lowered. For tendamistat, the friction coefficient in the Langevin equation is found to be around 40-60cm-1 for the low-indexed modes, compatible with literature. The fact that water has increased the friction and that on the other hand has lubrication effect at first sight contradicts. However, this comes about because water enhances the transitions between minima and forces the protein to reduce its already inherent inability to maintain oscillations observed in vacuum. Some of the frequencies lower than 10cm-1 are found to be overdamped, while those higher than 20cm-1 are slightly increased. As for the long-time dynamics in water, it is found that random-walk motion is maintained for approximately 200ps (about five times of that in vacuum) in the low-indexed modes, showing the lowering of energy barriers between the higher-level minima.

  18. Folding of a DNA Hairpin Loop Structure in Explicit Solvent Using Replica-Exchange Molecular Dynamics Simulations.

    SciTech Connect

    Kannan, Srinivasaraghavan; Zacharias, Martin W.

    2007-11-01

    The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. Hairpin loop structures are common motifs in folded nucleic acids. The 59-GCGCAGC sequence in DNA forms a characteristic and stable trinucleotide hairpin loop flanked by a two basepair stem helix. To better understand the structure formation of this hairpin loop motif in atomic detail, we employed replica-exchange molecular dynamics (RexMD) simulations starting from a single-stranded DNA conformation. In two independent 36 ns RexMD simulations, conformations in very close agreement with the experimental hairpin structure were sampled as dominant conformations (lowest free energy state) during the final phase of the RexMDs (;35% at the lowest temperature replica). Simultaneous compaction and accumulation of folded structures were observed. Comparison of the GCA trinucleotides from early stages of the simulations with the folded topology indicated a variety of central loop conformations, but arrangements close to experiment that are sampled before the fully folded structure also appeared. Most of these intermediates included a stacking of the C2 and G3 bases, which was further stabilized by hydrogen bonding to the A5 base and a strongly bound water molecule bridging the C2 and A5 in the DNA minor groove. The simulations suggest a folding mechanism where these intermediates can rapidly proceed toward the fully folded hairpin and emphasize the importance of loop and stem nucleotide interactions for hairpin folding. In one simulation, a loop motif with G3 in syn conformation (dihedral flip at N-glycosidic bond) accumulated, resulting in a misfolded hairpin. Such conformations may correspond to long-lived trapped states that have been postulated to account for the folding kinetics of nucleic acid hairpins that are slower than expected for a semiflexible polymer of the same size.

  19. Solvent effects on polymer sorting of carbon nanotubes with applications in printed electronics.

    PubMed

    Wang, Huiliang; Hsieh, Bing; Jiménez-Osés, Gonzalo; Liu, Peng; Tassone, Christopher J; Diao, Ying; Lei, Ting; Houk, Kendall N; Bao, Zhenan

    2015-01-07

    Regioregular poly(3-alkylthiophene) (P3AT) polymers have been previously reported for the selective, high-yield dispersion of semiconducting single-walled carbon nanotubes (SWCNTs) in toluene. Here, five alternative solvents are investigated, namely, tetrahydrofuran, decalin, tetralin, m-xylene, and o-xylene, for the dispersion of SWCNTs by poly(3-dodecylthiophene) P3DDT. The dispersion yield could be increased to over 40% using decalin or o-xylene as the solvents while maintaining high selectivity towards semiconducting SWCNTs. Molecular dynamics (MD) simulations in explicit solvents are used to explain the improved sorting yield. In addition, a general mechanism is proposed to explain the selective dispersion of semiconducting SWCNTs by conjugated polymers. The possibility to perform selective sorting of semiconducting SWCNTs using various solvents provides a greater diversity of semiconducting SWCNT ink properties, such as boiling point, viscosity, and surface tension as well as toxicity. The efficacy of these new semiconducting SWCNT inks is demonstrated by using the high boiling point and high viscosity solvent tetralin for inkjet-printed transistors, where solvent properties are more compatible with the inkjet printing head and improved droplet formation.

  20. Improving the Efficiency of Non-equilibrium Sampling in the Aqueous Environment via Implicit-Solvent Simulations.

    PubMed

    Liu, Hui; Chen, Fu; Sun, Huiyong; Li, Dan; Hou, Tingjun

    2017-04-11

    By means of estimators based on non-equilibrium work, equilibrium free energy differences or potentials of mean force (PMFs) of a system of interest can be computed from biased molecular dynamics (MD) simulations. The approach, however, is often plagued by slow conformational sampling and poor convergence, especially when the solvent effects are taken into account. Here, as a possible way to alleviate the problem, several widely used implicit-solvent models, which are derived from the analytic generalized Born (GB) equation and implemented in the AMBER suite of programs, were employed in free energy calculations based on non-equilibrium work and evaluated for their abilities to emulate explicit water. As a test case, pulling MD simulations were carried out on an alanine polypeptide with different solvent models and protocols, followed by comparisons of the reconstructed PMF profiles along the unfolding coordinate. The results show that when employing the non-equilibrium work method, sampling with an implicit-solvent model is several times faster and, more importantly, converges more rapidly than that with explicit water due to reduction of dissipation. Among the assessed GB models, the Neck variants outperform the OBC and HCT variants in terms of accuracy, whereas their computational costs are comparable. In addition, for the best-performing models, the impact of the solvent-accessible surface area (SASA) dependent nonpolar solvation term was also examined. The present study highlights the advantages of implicit-solvent models for non-equilibrium sampling.

  1. Firing of pulverized solvent refined coal

    DOEpatents

    Derbidge, T. Craig; Mulholland, James A.; Foster, Edward P.

    1986-01-01

    An air-purged burner for the firing of pulverized solvent refined coal is constructed and operated such that the solvent refined coal can be fired without the coking thereof on the burner components. The air-purged burner is designed for the firing of pulverized solvent refined coal in a tangentially fired boiler.

  2. Solvent Extraction of Furfural From Biomass

    NASA Technical Reports Server (NTRS)

    Humphrey, M. F.

    1984-01-01

    Solvent-extraction method reduces energy required to remove furfural produced during acid hydrolysis of biomass. Acid hydrolysis performed in vessel containing both solvents and reacting ingredients. With intimate contact between solvents and aqueous hydrolyis liqour, furfural removed form liquor almost as fast as it forms.

  3. The solvent component of macromolecular crystals

    SciTech Connect

    Weichenberger, Christian X.; Kantardjieff, Katherine; Rupp, Bernhard

    2015-04-30

    On average, the mother liquor or solvent and its constituents occupy about 50% of a macromolecular crystal. Ordered as well as disordered solvent components need to be accurately accounted for in modelling and refinement, often with considerable complexity. The mother liquor from which a biomolecular crystal is grown will contain water, buffer molecules, native ligands and cofactors, crystallization precipitants and additives, various metal ions, and often small-molecule ligands or inhibitors. On average, about half the volume of a biomolecular crystal consists of this mother liquor, whose components form the disordered bulk solvent. Its scattering contributions can be exploited in initial phasing and must be included in crystal structure refinement as a bulk-solvent model. Concomitantly, distinct electron density originating from ordered solvent components must be correctly identified and represented as part of the atomic crystal structure model. Herein, are reviewed (i) probabilistic bulk-solvent content estimates, (ii) the use of bulk-solvent density modification in phase improvement, (iii) bulk-solvent models and refinement of bulk-solvent contributions and (iv) modelling and validation of ordered solvent constituents. A brief summary is provided of current tools for bulk-solvent analysis and refinement, as well as of modelling, refinement and analysis of ordered solvent components, including small-molecule ligands.

  4. Albumin (BSA) Adsorption over Graphene in Aqueous Environment: Influence of Orientation, Adsorption Protocol, and Solvent Treatment.

    PubMed

    Vilhena, J G; Rubio-Pereda, Pamela; Vellosillo, Perceval; Serena, P A; Pérez, Rubén

    2016-02-23

    We report 150 ns explicit solvent MD simulations of the adsorption on graphene of albumin (BSA) in two orientations and using two different adsorption protocols, i.e., free and forced adsorption. Our results show that free adsorption occurs with little structural rearrangements. Even taking adsorption to an extreme, by forcing it with a 5 nN downward force applied during the initial 20 ns, we show that along a particular orientation BSA is able to preserve the structural properties of the majority of its binding sites. Furthermore, in all the cases considered in this work, the ibuprofen binding site has shown a strong resilience to structural changes. Finally, we compare these results with implicit solvent simulations and find that the latter predicts an extreme protein unfolding upon adsorption. The origin of this discrepancy is attributed to a poor description of the water entropic forces at interfaces in the implicit solvent methods.

  5. Solvents effects on the mechanism of cellulose hydrolysis: A QM/MM study.

    PubMed

    Loerbroks, Claudia; Heimermann, Andreas; Thiel, Walter

    2015-06-05

    This article reports a combined quantum mechanics/molecular mechanics (QM/MM) investigation on the acid hydrolysis of cellulose in water using two different models, cellobiose and a 40-unit cellulose chain. The explicitly treated solvent molecules strongly influence the conformations, intramolecular hydrogen bonds, and exoanomeric effects in these models. As these features are largely responsible for the barrier to cellulose hydrolysis, the present QM/MM results for the pathways and reaction intermediates in water are expected to be more realistic than those from a former density functional theory (DFT) study with implicit solvent (CPCM). However, in a qualitative sense, there is reasonable agreement between the DFT/CPCM and QM/MM predictions for the reaction mechanism. Differences arise mainly from specific solute-solvent hydrogen bonds that are only captured by QM/MM and not by DFT/CPCM.

  6. Moderators of the Relationship between Implicit and Explicit Evaluation

    PubMed Central

    Nosek, Brian A.

    2005-01-01

    Automatic and controlled modes of evaluation sometimes provide conflicting reports of the quality of social objects. This paper presents evidence for four moderators of the relationship between automatic (implicit) and controlled (explicit) evaluations. Implicit and explicit preferences were measured for a variety of object pairs using a large sample. The average correlation was r = .36, and 52 of the 57 object pairs showed a significant positive correlation. Results of multilevel modeling analyses suggested that: (a) implicit and explicit preferences are related, (b) the relationship varies as a function of the objects assessed, and (c) at least four variables moderate the relationship – self-presentation, evaluative strength, dimensionality, and distinctiveness. The variables moderated implicit-explicit correspondence across individuals and accounted for much of the observed variation across content domains. The resulting model of the relationship between automatic and controlled evaluative processes is grounded in personal experience with the targets of evaluation. PMID:16316292

  7. Explicit and Implicit Emotion Regulation: A Dual-Process Framework

    PubMed Central

    Gyurak, Anett; Gross, James J.; Etkin, Amit

    2012-01-01

    It is widely acknowledged that emotions can be regulated in an astonishing variety of ways. Most research to date has focused on explicit (effortful) forms of emotion regulation. However, there is growing research interest in implicit (automatic) forms of emotion regulation. To organize emerging findings, we present a dual-process framework that integrates explicit and implicit forms of emotion regulation, and argue that both forms of regulation are necessary for well-being. In the first section of this review, we provide a broad overview of the construct of emotion regulation, with an emphasis on explicit and implicit processes. In the second section, we focus on explicit emotion regulation, considering both neural mechanisms that are associated with these processes and their experiential and physiological consequences. In the third section, we turn to several forms of implicit emotion regulation, and integrate the burgeoning literature in this area. We conclude by outlining open questions and areas for future research. PMID:21432682

  8. Implicit and explicit learning in individuals with agrammatic aphasia.

    PubMed

    Schuchard, Julia; Thompson, Cynthia K

    2014-06-01

    Implicit learning is a process of acquiring knowledge that occurs without conscious awareness of learning, whereas explicit learning involves the use of overt strategies. To date, research related to implicit learning following stroke has been largely restricted to the motor domain and has rarely addressed implications for language. The present study investigated implicit and explicit learning of an auditory word sequence in 10 individuals with stroke-induced agrammatic aphasia and 18 healthy age-matched participants using an adaptation of the Serial Reaction Time task. Individuals with aphasia showed significant learning under implicit, but not explicit, conditions, whereas age-matched participants learned under both conditions. These results suggest significant implicit learning ability in agrammatic aphasia. Furthermore, results of an auditory sentence span task indicated working memory deficits in individuals with agrammatic aphasia, which are discussed in relation to explicit and implicit learning processes.

  9. Multidimensional explicit difference schemes for hyperbolic conservation laws

    NASA Technical Reports Server (NTRS)

    Van Leer, B.

    1984-01-01

    First- and second-order explicit difference schemes are derived for a three-dimensional hyperbolic system of conservation laws, without recourse to dimensional factorization. All schemes are upwind biased and optimally stable.

  10. Multidimensional explicit difference schemes for hyperbolic conservation laws

    NASA Technical Reports Server (NTRS)

    Vanleer, B.

    1983-01-01

    First and second order explicit difference schemes are derived for a three dimensional hyperbolic system of conservation laws, without recourse to dimensional factorization. All schemes are upwind (backward) biased and optimally stable.

  11. Solvent cleaning system and method for removing contaminants from solvent used in resin recycling

    DOEpatents

    Bohnert, George W.; Hand, Thomas E.; DeLaurentiis, Gary M.

    2009-01-06

    A two step solvent and carbon dioxide based system that produces essentially contaminant-free synthetic resin material and which further includes a solvent cleaning system for periodically removing the contaminants from the solvent so that the solvent can be reused and the contaminants can be collected and safely discarded in an environmentally safe manner.

  12. Solute-solvent and solvent-solvent interactions in the preferential solvation of 4-[4-(dimethylamino)styryl]-1-methylpyridinium iodide in 24 binary solvent mixtures.

    PubMed

    Bevilaqua, Tharly; Gonçalves, Thaini F; Venturini, Cristina de G; Machado, Vanderlei G

    2006-11-01

    The molar transition energy (E(T)) polarity values for the dye 4-[4-(dimethylamino)styryl]-1-methylpyridinium iodide were collected in binary mixtures comprising a hydrogen-bond accepting (HBA) solvent (acetone, acetonitrile, dimethyl sulfoxide (DMSO), and N,N-dimethylformamide (DMF)) and a hydrogen-bond donating (HBD) solvent (water, methanol, ethanol, propan-2-ol, and butan-1-ol). Data referring to mixtures of water with alcohols were also analyzed. These data were used in the study of the preferential solvation of the probe, in terms of both solute-solvent and solvent-solvent interactions. These latter interactions are of importance in explaining the synergistic behavior observed for many mixed solvent systems. All data were successfully fitted to a model based on solvent-exchange equilibria. The E(T) values of the dye dissolved in the solvents show that the position of the solvatochromic absorption band of the dye is dependent on the medium polarity. The solvation of the dye in HBA solvents occurs with a very important contribution from ion-dipole interactions. In HBD solvents, the hydrogen bonding between the dimethylamino group in the dye and the OH group in the solvent plays an important role in the solvation of the dye. The interaction of the hydroxylic solvent with the other component in the mixture can lead to the formation of hydrogen-bonded complexes, which solvate the dye using a lower polar moiety, i.e. alkyl groups in the solvents. The dye has a hydrophobic nature and a dimethylamino group with a minor capability for hydrogen bonding with the medium in comparison with the phenolate group present in Reichardt's pyridiniophenolate. Thus, the probe is able to detect solvent-solvent interactions, which are implicit to the observed synergistic behavior.

  13. Implicit and explicit representations of hand position in tool use.

    PubMed

    Rand, Miya K; Heuer, Herbert

    2013-01-01

    Understanding the interactions of visual and proprioceptive information in tool use is important as it is the basis for learning of the tool's kinematic transformation and thus skilled performance. This study investigated how the CNS combines seen cursor positions and felt hand positions under a visuo-motor rotation paradigm. Young and older adult participants performed aiming movements on a digitizer while looking at rotated visual feedback on a monitor. After each movement, they judged either the proprioceptively sensed hand direction or the visually sensed cursor direction. We identified asymmetric mutual biases with a strong visual dominance. Furthermore, we found a number of differences between explicit and implicit judgments of hand directions. The explicit judgments had considerably larger variability than the implicit judgments. The bias toward the cursor direction for the explicit judgments was about twice as strong as for the implicit judgments. The individual biases of explicit and implicit judgments were uncorrelated. Biases of these judgments exhibited opposite sequential effects. Moreover, age-related changes were also different between these judgments. The judgment variability was decreased and the bias toward the cursor direction was increased with increasing age only for the explicit judgments. These results indicate distinct explicit and implicit neural representations of hand direction, similar to the notion of distinct visual systems.

  14. Batch extracting process using magneticparticle held solvents

    DOEpatents

    Nunez, Luis; Vandergrift, George F.

    1995-01-01

    A process for selectively removing metal values which may include catalytic values from a mixture containing same, wherein a magnetic particle is contacted with a liquid solvent which selectively dissolves the metal values to absorb the liquid solvent onto the magnetic particle. Thereafter the solvent-containing magnetic particles are contacted with a mixture containing the heavy metal values to transfer metal values into the solvent carried by the magnetic particles, and then magnetically separating the magnetic particles. Ion exchange resins may be used for selective solvents.

  15. Aminosilicone solvents for CO(2) capture.

    PubMed

    Perry, Robert J; Grocela-Rocha, Teresa A; O'Brien, Michael J; Genovese, Sarah; Wood, Benjamin R; Lewis, Larry N; Lam, Hubert; Soloveichik, Grigorii; Rubinsztajn, Malgorzata; Kniajanski, Sergei; Draper, Sam; Enick, Robert M; Johnson, J Karl; Xie, Hong-bin; Tapriyal, Deepak

    2010-08-23

    This work describes the first report of the use of an aminosilicone solvent mix for the capture of CO(2). To maintain a liquid state, a hydroxyether co-solvent was employed which allowed enhanced physisorption of CO(2) in the solvent mixture. Regeneration of the capture solvent system was demonstrated over 6 cycles and absorption isotherms indicate a 25-50 % increase in dynamic CO(2) capacity over 30 % MEA. In addition, proof of concept for continuous CO(2) absorption was verified. Additionally, modeling to predict heats of reaction of aminosilicone solvents with CO(2) was in good agreement with experimental results.

  16. Interrogating surface state of isolated and agglomerated PbS quantum dots with solvent-induced stress.

    PubMed

    Sher, Pin-Hao; Wang, Juen-Kai

    2017-04-21

    Applications of quantum dots (QDs) are often obstructed by the associated surface electronic states that quench photoluminescence (PL) and hinder charge transport. Preventing this is still largely being stymied owing to the lack of means to regulate their presence. Dispersing PbS QDs in toluene, we show that varying the solvent temperature offers a way of modulating their surface electronic state. A comprehensive energy-transfer model explains all the anomalous temperature-dependent behavior of the absorption and PL, explicitly revealing the PL quenching dynamics of isolated QDs due to the induced surface state by imposing solvent stress on their surface ligands. This study demonstrates that the local stress induced by a solvent can serve as a 'switch' for the surface electronic states of QDs, which is enabled by the well-studied thermo-physical properties of a liquid solvent.

  17. Interrogating surface state of isolated and agglomerated PbS quantum dots with solvent-induced stress

    NASA Astrophysics Data System (ADS)

    Sher, Pin-Hao; Wang, Juen-Kai

    2017-04-01

    Applications of quantum dots (QDs) are often obstructed by the associated surface electronic states that quench photoluminescence (PL) and hinder charge transport. Preventing this is still largely being stymied owing to the lack of means to regulate their presence. Dispersing PbS QDs in toluene, we show that varying the solvent temperature offers a way of modulating their surface electronic state. A comprehensive energy-transfer model explains all the anomalous temperature-dependent behavior of the absorption and PL, explicitly revealing the PL quenching dynamics of isolated QDs due to the induced surface state by imposing solvent stress on their surface ligands. This study demonstrates that the local stress induced by a solvent can serve as a ‘switch’ for the surface electronic states of QDs, which is enabled by the well-studied thermo-physical properties of a liquid solvent.

  18. Accurate calculation of conformational free energy differences in explicit water: the confinement-solvation free energy approach.

    PubMed

    Esque, Jeremy; Cecchini, Marco

    2015-04-23

    The calculation of the free energy of conformation is key to understanding the function of biomolecules and has attracted significant interest in recent years. Here, we present an improvement of the confinement method that was designed for use in the context of explicit solvent MD simulations. The development involves an additional step in which the solvation free energy of the harmonically restrained conformers is accurately determined by multistage free energy perturbation simulations. As a test-case application, the newly introduced confinement/solvation free energy (CSF) approach was used to compute differences in free energy between conformers of the alanine dipeptide in explicit water. The results are in excellent agreement with reference calculations based on both converged molecular dynamics and umbrella sampling. To illustrate the general applicability of the method, conformational equilibria of met-enkephalin (5 aa) and deca-alanine (10 aa) in solution were also analyzed. In both cases, smoothly converged free-energy results were obtained in agreement with equilibrium sampling or literature calculations. These results demonstrate that the CSF method may provide conformational free-energy differences of biomolecules with small statistical errors (below 0.5 kcal/mol) and at a moderate computational cost even with a full representation of the solvent.

  19. Solvent cavitation under solvophobic confinement

    NASA Astrophysics Data System (ADS)

    Ashbaugh, Henry S.

    2013-08-01

    The stability of liquids under solvophobic confinement can tip in favor of the vapor phase, nucleating a liquid-to-vapor phase transition that induces attractive forces between confining surfaces. In the case of water adjacent to hydrophobic surfaces, experimental and theoretical evidence support confinement-mediated evaporation stabilization of biomolecular and colloidal assemblies. The macroscopic thermodynamic theory of cavitation under confinement establishes the connection between the size of the confining surfaces, interfacial free energies, and bulk solvent pressure with the critical evaporation separation and interfacial forces. While molecular simulations have confirmed the broad theoretical trends, a quantitative comparison based on independent measurements of the interfacial free energies and liquid-vapor coexistence properties has, to the best of our knowledge, not yet been performed. To overcome the challenges of simulating a large number of systems to validate scaling predictions for a three-dimensional fluid, we simulate both the forces and liquid-vapor coexistence properties of a two-dimensional Lennard-Jones fluid confined between solvophobic plates over a range of plate sizes and reservoir pressures. Our simulations quantitatively agree with theoretical predictions for solvent-mediated forces and critical evaporation separations once the length dependence of the solvation free energy of an individual confining plate is taken into account. The effective solid-liquid line tension length dependence results from molecular scale correlations for solvating microscopic plates and asymptotically decays to the macroscopic value for plates longer than 150 solvent diameters. The success of the macroscopic thermodynamic theory at describing two-dimensional liquids suggests application to surfactant monolayers to experimentally confirm confinement-mediated cavitation.

  20. Advanced integrated solvent extraction systems

    SciTech Connect

    Horwitz, E.P.; Dietz, M.L.; Leonard, R.A.

    1997-10-01

    Advanced integrated solvent extraction systems are a series of novel solvent extraction (SX) processes that will remove and recover all of the major radioisotopes from acidic-dissolved sludge or other acidic high-level wastes. The major focus of this effort during the last 2 years has been the development of a combined cesium-strontium extraction/recovery process, the Combined CSEX-SREX Process. The Combined CSEX-SREX Process relies on a mixture of a strontium-selective macrocyclic polyether and a novel cesium-selective extractant based on dibenzo 18-crown-6. The process offers several potential advantages over possible alternatives in a chemical processing scheme for high-level waste treatment. First, if the process is applied as the first step in chemical pretreatment, the radiation level for all subsequent processing steps (e.g., transuranic extraction/recovery, or TRUEX) will be significantly reduced. Thus, less costly shielding would be required. The second advantage of the Combined CSEX-SREX Process is that the recovered Cs-Sr fraction is non-transuranic, and therefore will decay to low-level waste after only a few hundred years. Finally, combining individual processes into a single process will reduce the amount of equipment required to pretreat the waste and therefore reduce the size and cost of the waste processing facility. In an ongoing collaboration with Lockheed Martin Idaho Technology Company (LMITCO), the authors have successfully tested various segments of the Advanced Integrated Solvent Extraction Systems. Eichrom Industries, Inc. (Darien, IL) synthesizes and markets the Sr extractant and can supply the Cs extractant on a limited basis. Plans are under way to perform a test of the Combined CSEX-SREX Process with real waste at LMITCO in the near future.

  1. SOLVENT EXTRACTION PROCESS FOR PLUTONIUM

    DOEpatents

    Seaborg, G.T.

    1959-04-14

    The separation of plutonium from aqueous inorganic acid solutions by the use of a water immiscible organic extractant liquid is described. The plutonium must be in the oxidized state, and the solvents covered by the patent include nitromethane, nitroethane, nitropropane, and nitrobenzene. The use of a salting out agents such as ammonium nitrate in the case of an aqueous nitric acid solution is advantageous. After contacting the aqueous solution with the organic extractant, the resulting extract and raffinate phases are separated. The plutonium may be recovered by any suitable method.

  2. DFT-based simulations of amide I' IR spectra of a small protein in solution using empirical electrostatic map with a continuum solvent model.

    PubMed

    Welch, William R W; Kubelka, Jan

    2012-09-06

    A continuum solvent model was tested for simulations of amide I' IR spectra for a 40-residue subdomain of P22 viral coat protein in aqueous solution. Spectra obtained using DFT (BPW91/6-31G**) parameters for a reduced all-Ala representation of the protein were corrected by an electrostatic potential map obtained from the solvent cavity surface and AMBER99 side-chain atom partial charges. Various cavity sizes derived from van der Waals atomic radii with an added effective solvent radius up to 2.0 Å were tested. The interplay of the side-chain and solvent electrostatic effects was investigated by considering the side chains and solvent separately as well as together. The sensitivity to side-chain conformational fluctuations and to the parametrization of C(β) group partial charges was also tested. Simulation results were compared to the experimental amide I' spectra of P22 subdomain, including two (13)C isotopically edited variants, as well as to the previous simulations based on the molecular dynamics trajectory in explicit solvent. For small cavity sizes, between van der Waals and that with added solvent radius of 0.5 Å, better qualitative agreement with experiment was obtained than with the explicit solvent representation, in particular for the (13)C-labeled spectra. Larger protein cavities led to progressively worse predictions due to increasingly stronger electrostatic effects of side chains, which could no longer be well compensated for by the solvent potential. Balance between side-chain and solvent electrostatic effects is important in determining the width and shape of the simulated amide I', which is also virtually unaffected by side-chain-geometry fluctuations. The continuum solvent model combined with the electrostatic map is a computationally efficient and potentially robust approach for the simulations of IR spectra of proteins in solution.

  3. Factors influencing university students' explicit and implicit sexual double standards.

    PubMed

    Sakaluk, John K; Milhausen, Robin R

    2012-01-01

    Quantitative research has resulted in inconsistent evidence for the existence of a sexual double standard, leading Crawford and Popp ( 2003 ) to issue a call for methodological innovation. The implicit association test (IAT; Greenwald, McGhee, & Schwartz, 1998 ) is a measure that may provide a means to examine the double standard without the contamination of the demand characteristics and social desirability biases that plague self-report research (Marks & Fraley, 2005 ). The purpose of this study was to examine the factors influencing explicit and implicit double standards, and to examine the relationship between these explicit and implicit double standards, and levels of socially desirable responding. One hundred and three university students completed a sexual double standard IAT, an explicit measure of the double standard, and measures of socially desirable responding. Hierarchical regression analysis indicated that levels of socially desirable responding were not related to implicit or explicit double standards. Men endorsed a stronger explicit traditional double standard than women, whereas for implicit sexual standards, men demonstrated a relatively gender-neutral evaluation and women demonstrated a strong reverse double standard. These results suggest the existence of a complex double standard, and indicate that more research of sexual attitudes should include implicit measures.

  4. Perspective: Explicitly correlated electronic structure theory for complex systems

    NASA Astrophysics Data System (ADS)

    Grüneis, Andreas; Hirata, So; Ohnishi, Yu-ya; Ten-no, Seiichiro

    2017-02-01

    The explicitly correlated approach is one of the most important breakthroughs in ab initio electronic structure theory, providing arguably the most compact, accurate, and efficient ansatz for describing the correlated motion of electrons. Since Hylleraas first used an explicitly correlated wave function for the He atom in 1929, numerous attempts have been made to tackle the significant challenges involved in constructing practical explicitly correlated methods that are applicable to larger systems. These include identifying suitable mathematical forms of a correlated wave function and an efficient evaluation of many-electron integrals. R12 theory, which employs the resolution of the identity approximation, emerged in 1985, followed by the introduction of novel correlation factors and wave function ansätze, leading to the establishment of F12 theory in the 2000s. Rapid progress in recent years has significantly extended the application range of explicitly correlated theory, offering the potential of an accurate wave-function treatment of complex systems such as photosystems and semiconductors. This perspective surveys explicitly correlated electronic structure theory, with an emphasis on recent stochastic and deterministic approaches that hold significant promise for applications to large and complex systems including solids.

  5. The solvent component of macromolecular crystals

    PubMed Central

    Weichenberger, Christian X.; Afonine, Pavel V.; Kantardjieff, Katherine; Rupp, Bernhard

    2015-01-01

    The mother liquor from which a biomolecular crystal is grown will contain water, buffer molecules, native ligands and cofactors, crystallization precipitants and additives, various metal ions, and often small-molecule ligands or inhibitors. On average, about half the volume of a biomolecular crystal consists of this mother liquor, whose components form the disordered bulk solvent. Its scattering contributions can be exploited in initial phasing and must be included in crystal structure refinement as a bulk-solvent model. Concomitantly, distinct electron density originating from ordered solvent components must be correctly identified and represented as part of the atomic crystal structure model. Herein, are reviewed (i) probabilistic bulk-solvent content estimates, (ii) the use of bulk-solvent density modification in phase improvement, (iii) bulk-solvent models and refinement of bulk-solvent contributions and (iv) modelling and validation of ordered solvent constituents. A brief summary is provided of current tools for bulk-solvent analysis and refinement, as well as of modelling, refinement and analysis of ordered solvent components, including small-molecule ligands. PMID:25945568

  6. Dynamics around solutes and solute-solvent complexes in mixed solvents.

    PubMed

    Kwak, Kyungwon; Park, Sungnam; Fayer, M D

    2007-09-04

    Ultrafast 2D-IR vibrational echo experiments, IR pump-probe experiments, and FT-IR spectroscopy of the hydroxyl stretch of phenol-OD in three solvents, CCl4, mesitylene (1, 3, 5 trimethylbenzene), and the mixed solvent of mesitylene and CCl4 (0.83 mole fraction CCl4), are used to study solute-solvent dynamics via observation of spectral diffusion. Phenol forms a complex with Mesitylene. In the mesitylene solution, there is only complexed phenol; in the CCl4 solution, there is only uncomplexed phenol; and in the mixed solvent, both phenol species are present. Dynamics of the free phenol in CCl4 or the mixed solvent are very similar, and dynamics of the complex in mesitylene and in the mixed solvent are very similar. However, there are differences in the slowest time scale dynamics between the pure solvents and the mixed solvents. The mixed solvent produces slower dynamics that are attributed to first solvent shell solvent composition variations. The composition variations require a longer time to randomize than is required in the pure solvents, where only density variations occur. The experimental results and recent MD simulations indicate that the solvent structure around the solute may be different from the mixed solvent's mole fraction.

  7. Asphaltene aggregation in organic solvents.

    PubMed

    Oh, Kyeongseok; Ring, Terry A; Deo, Milind D

    2004-03-01

    Asphaltenic solids formed in the Rangely field in the course of a carbon dioxide flood and heptane insolubles in the oil from the same field were used in this study. Four different solvents were used to dissolve the asphaltenes. Near-infrared (NIR) spectroscopy was used to determine the onset of asphaltene precipitation by heptane titration. When the onset values were plotted versus asphaltene concentrations, distinct break points (called critical aggregation concentrations (CAC) in this paper) were observed. CACs for the field asphaltenes dissolved in toluene, trichloroethylene, tetrahydrofuran, and pyridine occurred at concentrations of 3.0, 3.7, 5.0, and 8.2 g/l, respectively. CACs are observed at similar concentrations as critical micelle concentrations (CMC) for the asphaltenes in the solvents employed and can be interpreted to be the points at which rates of asphaltene aggregations change. CMC values of asphaltenes determined from surface tension measurements (in pyridine and TCE) were slightly higher than the CAC values measured by NIR onset measurements. The CAC for heptane-insoluble asphaltenes in toluene was 3.1 g/l. Thermal gravimetric analysis (TGA) and elemental compositions of the two asphaltenes showed that the H/C ratio of the heptane-insoluble asphaltenes was higher and molecular weight (measured by vapor pressure osmometry) was lower.

  8. Explicit infiltration equations and the Lambert W-function

    NASA Astrophysics Data System (ADS)

    Parlange, J.-Y.; Barry, D. A.; Haverkamp, R.

    The Green and Ampt infiltration formula, as well as the Talsma and Parlange formula, are two-parameter equations that are both expressible in terms of Lambert W-functions. These representations are used to derive explicit, simple and accurate approximations for each case. The two infiltration formulas are limiting cases that can be deduced from an existing three-parameter infiltration equation, the third parameter allowing for interpolation between the limiting cases. Besides the limiting cases, there is another case for which the three-parameter infiltration equation yields an exact solution. The three-parameter equation can be solved by fixed-point iteration, a scheme which can be exploited to obtain a sequence of increasingly complex explicit infiltration equations. For routine use, a simple, explicit approximation to the three-parameter infiltration equation is derived. This approximation eliminates the need to iterate for most practical circumstances.

  9. The time course of explicit and implicit categorization.

    PubMed

    Smith, J David; Zakrzewski, Alexandria C; Herberger, Eric R; Boomer, Joseph; Roeder, Jessica L; Ashby, F Gregory; Church, Barbara A

    2015-10-01

    Contemporary theory in cognitive neuroscience distinguishes, among the processes and utilities that serve categorization, explicit and implicit systems of category learning that learn, respectively, category rules by active hypothesis testing or adaptive behaviors by association and reinforcement. Little is known about the time course of categorization within these systems. Accordingly, the present experiments contrasted tasks that fostered explicit categorization (because they had a one-dimensional, rule-based solution) or implicit categorization (because they had a two-dimensional, information-integration solution). In Experiment 1, participants learned categories under unspeeded or speeded conditions. In Experiment 2, they applied previously trained category knowledge under unspeeded or speeded conditions. Speeded conditions selectively impaired implicit category learning and implicit mature categorization. These results illuminate the processing dynamics of explicit/implicit categorization.

  10. Exploring large-scale phenomena in composite membranes through an efficient implicit-solvent model

    NASA Astrophysics Data System (ADS)

    Laradji, Mohamed; Kumar, P. B. Sunil; Spangler, Eric J.

    2016-07-01

    Several microscopic and mesoscale models have been introduced in the past to investigate various phenomena in lipid membranes. Most of these models account for the solvent explicitly. Since in a typical molecular dynamics simulation, the majority of particles belong to the solvent, much of the computational effort in these simulations is devoted for calculating forces between solvent particles. To overcome this problem, several implicit-solvent mesoscale models for lipid membranes have been proposed during the last few years. In the present article, we review an efficient coarse-grained implicit-solvent model we introduced earlier for studies of lipid membranes. In this model, lipid molecules are coarse-grained into short semi-flexible chains of beads with soft interactions. Through molecular dynamics simulations, the model is used to investigate the thermal, structural and elastic properties of lipid membranes. We will also review here few studies, based on this model, of the phase behavior of nanoscale liposomes, cytoskeleton-induced blebbing in lipid membranes, as well as nanoparticles wrapping and endocytosis by tensionless lipid membranes. Topical Review article submitted to the Journal of Physics D: Applied Physics, May 9, 2016

  11. Dynamic implicit-solvent coarse-grained models of lipid bilayer membranes: fluctuating hydrodynamics thermostat.

    PubMed

    Wang, Yaohong; Sigurdsson, Jon Karl; Brandt, Erik; Atzberger, Paul J

    2013-08-01

    We introduce a thermostat based on fluctuating hydrodynamics for dynamic simulations of implicit-solvent coarse-grained models of lipid bilayer membranes. We show our fluctuating hydrodynamics approach captures interesting correlations in the dynamics of lipid bilayer membranes that are missing in simulations performed using standard Langevin dynamics. Our momentum conserving thermostat accounts for solvent-mediated momentum transfer by coupling coarse-grained degrees of freedom to stochastic continuum fields that account for both the solvent hydrodynamics and thermal fluctuations. We present both a general framework and specific methods to couple the particle and continuum degrees of freedom in a manner consistent with statistical mechanics and amenable to efficient computational simulation. For self-assembled vesicles, we study the diffusivity of lipids and their spatial correlations. We find the hydrodynamic coupling yields within the bilayer interesting correlations between diffusing lipids that manifest as a vortex-like structure similar to those observed in explicit-solvent simulations. We expect the introduced fluctuating hydrodynamics methods to provide a way to extend implicit-solvent models for use in a wide variety of dynamic studies.

  12. Accurate thermochemistry from explicitly correlated distinguishable cluster approximation.

    PubMed

    Kats, Daniel; Kreplin, David; Werner, Hans-Joachim; Manby, Frederick R

    2015-02-14

    An explicitly correlated version of the distinguishable-cluster approximation is presented and extensively benchmarked. It is shown that the usual F12-type explicitly correlated approaches are applicable to distinguishable-cluster theory with single and double excitations, and the results show a significant improvement compared to coupled-cluster theory with singles and doubles for closed and open-shell systems. The resulting method can be applied in a black-box manner to systems with single- and multireference character. Most noticeably, optimized geometries are of coupled-cluster singles and doubles with perturbative triples quality or even better.

  13. Comment on ``Analysis of optimal velocity model with explicit delay''

    NASA Astrophysics Data System (ADS)

    Davis, L. C.

    2002-09-01

    The effect of including an explicit delay time (due to driver reaction) on the optimal velocity model is studied. For a platoon of vehicles to avoid collisions, many-vehicle simulations demonstrate that delay times must be well below the critical delay time determined by a linear analysis for the response of a single vehicle. Safe platoons require rather small delay times, substantially smaller than typical reaction times of drivers. The present results do not support the conclusion of Bando et al. [M. Bando, K. Hasebe, K. Nakanishi, and A. Nakayama, Phys. Rev. E 58, 5429 (1998)] that explicit delay plays no essential role.

  14. Comment on "Analysis of optimal velocity model with explicit delay".

    PubMed

    Davis, L C

    2002-09-01

    The effect of including an explicit delay time (due to driver reaction) on the optimal velocity model is studied. For a platoon of vehicles to avoid collisions, many-vehicle simulations demonstrate that delay times must be well below the critical delay time determined by a linear analysis for the response of a single vehicle. Safe platoons require rather small delay times, substantially smaller than typical reaction times of drivers. The present results do not support the conclusion of Bando et al. [M. Bando, K. Hasebe, K. Nakanishi, and A. Nakayama, Phys. Rev. E 58, 5429 (1998)] that explicit delay plays no essential role.

  15. Explicit solution for Raman fiber laser using Lambert W function.

    PubMed

    Huang, Chaohong; Cai, Zhiping; Ye, Chenchun; Xu, Huiying

    2007-04-16

    In this paper, an approximate explicit solution for the first-order Raman fiber laser is obtained by using Lambert W function. Good agreement between the explicit solution and numerical simulation is demonstrated. Furthermore, the optimal design of Raman fiber laser is discussed using the proposed solution. The optimal values of fiber length, reflectivity of output fiber Bragg grating and power transfer efficiency are obtained under different pump power. There exists a certain tolerance of the optimal parameters, in which the output power decreases only slightly. The optimal fiber length and reflectivity of output FBG decrease with increasing pump power.

  16. Explicit solution for Raman fiber laser using Lambert W function

    NASA Astrophysics Data System (ADS)

    Huang, Chaohong; Cai, Zhiping; Ye, Chenchun; Xu, Huiying

    2007-04-01

    In this paper, an approximate explicit solution for the first-order Raman fiber laser is obtained by using Lambert W function. Good agreement between the explicit solution and numerical simulation is demonstrated. Furthermore, the optimal design of Raman fiber laser is discussed using the proposed solution. The optimal values of fiber length, reflectivity of output fiber Bragg grating and power transfer efficiency are obtained under different pump power. There exists a certain tolerance of the optimal parameters, in which the output power decreases only slightly. The optimal fiber length and reflectivity of output FBG decrease with increasing pump power.

  17. Common molecular mechanisms in explicit and implicit memory.

    PubMed

    Barco, Angel; Bailey, Craig H; Kandel, Eric R

    2006-06-01

    Cellular and molecular studies of both implicit and explicit memory suggest that experience-dependent modulation of synaptic strength and structure is a fundamental mechanism by which these memories are encoded and stored within the brain. In this review, we focus on recent advances in our understanding of two types of memory storage: (i) sensitization in Aplysia, a simple form of implicit memory, and (ii) formation of explicit spatial memories in the mouse hippocampus. These two processes share common molecular mechanisms that have been highly conserved through evolution.

  18. Modeling ductile dynamic fracture with ABAQUS/explicit

    SciTech Connect

    Anderson, C.A.; Turner, C.

    1996-05-01

    This paper illustrates the use of advanced constitutive models in ABAQUS/Explicit together with highly focused finite element meshes to simulate the propagation of a fracture in a ductile medium. A double edge-cracked specimen under far field dynamic tensile loading is analyzed, and shows both rectilinear motion or unstable oscillatory motion of the crack depending on the material property constraints. Results are also presented for a simulation of ASTM`s standard fracture test E399. Comparisons of ABAQUS/Explicit results with experiments or other analytical/numerical results are made.

  19. Solvent recovery system provides timely compliance solution

    SciTech Connect

    1996-11-01

    Hoechst Celanese Corp. (Coventry, Rhode Island) faced the challenge of meeting an Environmental Protection Agency (EPA) deadline for solvent recovery within one year. The company also had to ensure that a new solvent recovery system would satisfy Rhode Island state requirements. An initial search for the required technology was fruitless. Finally, MG Industries (Saint Charles, Missouri), an industrial gas supplier, was chosen for the job. Using CRYOSOLV, as the waste stream cools in the cryogenic condenser (heat exchanger), the solvents condense at temperatures below the dewpoint. The recovered solvent can be recycled into the process, while clean gas is vented to the atmosphere.

  20. Organic solvent use in enterprises in Japan.

    PubMed

    Nagasawa, Yasuhiro; Ukai, Hirohiko; Okamoto, Satoru; Samoto, Hajime; Itoh, Kenji; Moriguchi, Jiro; Sakuragi, Sonoko; Ohashi, Fumiko; Takada, Shiro; Kawakami, Tetsuya; Ikeda, Masayuki

    2011-01-01

    This study was initiated to elucidate possible changes in types of organic solvents (to be called solvents in short) used in enterprises in Japan through comparison of current solvent types with historical data since 1983. To investigate current situation in solvent use in enterprises, surveys were conducted during one year of 2009 to 2010. In total, workroom air samples in 1,497 unit workplaces with solvent use were analyzed in accordance with regulatory requirements. Typical use pattern of solvents was as mixtures, accounting for >70% of cases. Adhesives spreading (followed by adhesion) was relatively common in small-scale enterprises, whereas printing and painting work was more common in middle-scale ones, and solvent use for testing and research purpose was basically in large-scaled enterprises. Through-out printing, painting, surface coating and adhesive application, toluene was most common (being detected in 49 to 82% of workplaces depending on work types), whereas isopropyl alcohol was most common (49%) in degreasing, cleaning and wiping workplaces. Other commonly used solvents were methyl alcohol, ethyl acetate and acetone (33 to 37%). Comparison with historical data in Japan and literature-retrieved data outside of Japan all agreed with the observation that toluene is the most commonly used solvent. Application of trichloroethylene and 1,1,1-trichloroethane, once common in 1980s, has ceased to exist in recent years.

  1. Special Issue: "Organic Reactions in Green Solvents".

    PubMed

    Sperry, Jonathan; García-Álvarez, Joaquín

    2016-11-15

    To overcome the well-established drawbacks of conventional organic solvents (toxicity, non-biodegradability, flammability, accumulation in the atmosphere) remarkable research efforts have been recently devoted to the replacement of traditional organic reaction media by the so-called Green Solvents. In this sense, the choice of a safe, non-toxic, biorenewable and cheap reaction media is a crucial goal in organic synthesis. Thus, this Special Issue on "Organic Reactions in Green Solvents" has been aimed to showcase a series of stimulating contributions from international experts within different sub-areas of organic synthesis in Green Solvents (ranging from metal- to organo-catalyzed organic reactions).

  2. Process for hydrogenating coal and coal solvents

    DOEpatents

    Tarrer, Arthur R.; Shridharani, Ketan G.

    1983-01-01

    A novel process is described for the hydrogenation of coal by the hydrogenation of a solvent for the coal in which the hydrogenation of the coal solvent is conducted in the presence of a solvent hydrogenation catalyst of increased activity, wherein the hydrogenation catalyst is produced by reacting ferric oxide with hydrogen sulfide at a temperature range of 260.degree. C. to 315.degree. C. in an inert atmosphere to produce an iron sulfide hydrogenation catalyst for the solvent. Optimally, the reaction temperature is 275.degree. C. Alternately, the reaction can be conducted in a hydrogen atmosphere at 350.degree. C.

  3. A solvent tolerant isolate of Enterobacter aerogenes.

    PubMed

    Gupta, Anshu; Singh, Rajni; Khare, S K; Gupta, M N

    2006-01-01

    A solvent tolerant strain of Enterobacter aerogenes was isolated from soil by cyclohexane enrichment. Presence of cyclohexane (20%) in culture media prolonged the lag phase and caused reduction in biomass. Transmission electron micrographs showed convoluted cell membrane and accumulation of solvent in case of the cells grown in cyclohexane. The Enterobacter isolate was able to grow in the range of organic solvents having log P above 3.2 and also in presence of mercury, thus showing potential for treatment of solvent rich wastes.

  4. Solvent-driven chemical motor

    NASA Astrophysics Data System (ADS)

    Mitsumata, Tetsu; Ikeda, Kazuo; Gong, Jian Ping; Osada, Yoshihito

    1998-10-01

    A solvent-driven chemical motor using amphiphilic polymer gel has been fabricated. The driving force of the gel originates from the surface tension of spreading organic fluid which is pumped out by osmotic and hydrostatic pressures in the gel. A tetrahydrofurane-swollen gel equipped with a spouting hole made a controlled translational motion with a velocity of 77 mm/s or rotational motion with a maximum speed of 400 rpm and a torque of 10-9-10-7 Nm on the water surface. A generator to produce an electric power with a maximum electromotive force of 15 mV and electric power of 0.2 μW has also been constructed. The successful fabrication of gel motor may produce a new era of soft machine systems which work without pollution and unnecessary intermediates.

  5. Green Solvents for Precision Cleaning

    NASA Technical Reports Server (NTRS)

    Grandelli, Heather; Maloney, Phillip; DeVor, Robert; Surma, Jan; Hintze, Paul

    2013-01-01

    Aerospace machinery used in liquid oxygen (LOX) fuel systems must be precision cleaned to achieve a very low level of non-volatile residue (< 1 mg0.1 m2), especially flammable residue. Traditionally chlorofluorocarbons (CFCs) have been used in the precision cleaning of LOX systems, specifically CFC 113 (C2Cl3F3). CFCs have been known to cause the depletion of ozone and in 1987, were banned by the Montreal Protocol due to health, safety and environmental concerns. This has now led to the development of new processes in the precision cleaning of aerospace components. An ideal solvent-replacement is non-flammable, environmentally benign, non-corrosive, inexpensive, effective and evaporates completely, leaving no residue. Highlighted is a green precision cleaning process, which is contaminant removal using supercritical carbon dioxide as the environmentally benign solvent. In this process, the contaminant is dissolved in carbon dioxide, and the parts are recovered at the end of the cleaning process completely dry and ready for use. Typical contaminants of aerospace components include hydrocarbon greases, hydraulic fluids, silicone fluids and greases, fluorocarbon fluids and greases and fingerprint oil. Metallic aerospace components range from small nuts and bolts to much larger parts, such as butterfly valves 18 in diameter. A fluorinated grease, Krytox, is investigated as a model contaminant in these preliminary studies, and aluminum coupons are employed as a model aerospace component. Preliminary studies are presented in which the experimental parameters are optimized for removal of Krytox from aluminum coupons in a stirred-batch process. The experimental conditions investigated are temperature, pressure, exposure time and impeller speed. Temperatures of 308 - 423 K, pressures in the range of 8.3 - 41.4 MPa, exposure times between 5 - 60 min and impeller speeds of 0 - 1000 rpm were investigated. Preliminary results showed up to 86 cleaning efficiency with the

  6. Organic solvent-tolerant bacterium which secretes an organic solvent-stable proteolytic enzyme

    SciTech Connect

    Ogino, Hiroyasu; Yasui, Kiyoshi; Shiotani, Takashi

    1995-12-01

    A bacterial strain which can be grown in a medium containing organic solvents and can secrete a proteolytic enzyme was isolated and identified as Pseudomonas aeruginosa. The strain was derived by the following two-step procedures: high proteolytic enzyme producers were first isolated by the usual method, and then the organic solvent-tolerant microorganism was selected from these high-rate proteolytic enzyme producers. The proteolytic activity of the supernatant of the culture was stable in the presence of various organic solvents. The stability of the enzyme in the presence of organic solvents, of which the values of the logarithm of the partition coefficient (log P) were equal to or more than 3.2, was almost the same as that in the absence of organic solvents. It is expected that both the solvent-tolerant microorganism and the solvent-stable enzyme produced by this strain can be used as catalysts for reactions in the presence of organic solvents.

  7. Quantitation of buried contamination by use of solvents. [degradation of silicone polymers by amine solvents

    NASA Technical Reports Server (NTRS)

    Pappas, S. P.; Hsiao, Y. C.; Hill, L. W.

    1973-01-01

    Spore recovery form cured silicone potting compounds using amine solvents to degrade the cured polymers was investigated. A complete list of solvents and a description of the effect of each on two different silicone polymers is provided.

  8. Wide electrochemical window solvents for use in electrochemical devices and electrolyte solutions incorporating such solvents

    DOEpatents

    Angell, Charles Austen; Zhang, Sheng-Shui; Xu, Kang

    1998-01-01

    The present invention relates to electrolyte solvents for use in liquid or rubbery electrolyte solutions. Specifically, this invention is directed to boron-containing electrolyte solvents and boron-containing electrolyte solutions.

  9. Being Explicit about Modeling: A First Person Study in India

    ERIC Educational Resources Information Center

    Setty, Rohit Boggarm

    2013-01-01

    In this dissertation, I examine the work involved in teacher educator modeling. In particular, the study is concerned with modeling that aims to explicitly make teaching practices visible, learnable, and that does so in particularly demonstrative ways. One form of this type of modeling is what I term "dialogic modeling." The study…

  10. Explicit versus Implicit Social Cognition Testing in Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Callenmark, Björn; Kjellin, Lars; Rönnqvist, Louise; Bölte, Sven

    2014-01-01

    Although autism spectrum disorder is defined by reciprocal social-communication impairments, several studies have found no evidence for altered social cognition test performance. This study examined explicit (i.e. prompted) and implicit (i.e. spontaneous) variants of social cognition testing in autism spectrum disorder. A sample of 19 adolescents…

  11. Effect of explicit dimension instruction on speech category learning

    PubMed Central

    Chandrasekaran, Bharath; Yi, Han-Gyol; Smayda, Kirsten E.; Maddox, W. Todd

    2015-01-01

    Learning non-native speech categories is often considered a challenging task in adulthood. This difficulty is driven by cross-language differences in weighting critical auditory dimensions that differentiate speech categories. For example, previous studies have shown that differentiating Mandarin tonal categories requires attending to dimensions related to pitch height and direction. Relative to native speakers of Mandarin, the pitch direction dimension is under-weighted by native English speakers. In the current study, we examined the effect of explicit instructions (dimension instruction) on native English speakers' Mandarin tone category learning within the framework of a dual-learning systems (DLS) model. This model predicts that successful speech category learning is initially mediated by an explicit, reflective learning system that frequently utilizes unidimensional rules, with an eventual switch to a more implicit, reflexive learning system that utilizes multidimensional rules. Participants were explicitly instructed to focus and/or ignore the pitch height dimension, the pitch direction dimension, or were given no explicit prime. Our results show that instruction instructing participants to focus on pitch direction, and instruction diverting attention away from pitch height resulted in enhanced tone categorization. Computational modeling of participant responses suggested that instruction related to pitch direction led to faster and more frequent use of multidimensional reflexive strategies, and enhanced perceptual selectivity along the previously underweighted pitch direction dimension. PMID:26542400

  12. Stable explicit schemes for equations of Schroedinger type

    NASA Technical Reports Server (NTRS)

    Mickens, Ronald E.

    1989-01-01

    A method for constructing explicit finite-difference schemes which can be used to solve Schroedinger-type partial-differential equations is presented. A forward Euler scheme that is conditionally stable is given by the procedure. The results presented are based on the analysis of the simplest Schroedinger type equation.

  13. Flexibles Grouping, Explicit Reading Instruction in Elementary School

    ERIC Educational Resources Information Center

    Dubé, France; Dorval, Catherine; Bessette, Lyne

    2013-01-01

    The objective of this collaborative research is to evaluate the impact of a pedagogical intervention that combines flexible grouping and explicit instruction of reading comprehension strategies. The development of competencies is spread over a two years interval. However, despite this quite long implementation period, several Quebec students still…

  14. Comparing Switch Costs: Alternating Runs and Explicit Cuing

    ERIC Educational Resources Information Center

    Altmann, Erik M.

    2007-01-01

    The task-switching literature routinely conflates different operational definitions of switch cost, its predominant behavioral measure. This article is an attempt to draw attention to differences between the two most common definitions, alternating-runs switch cost (ARS) and explicit-cuing switch cost (ECS). ARS appears to include both the costs…

  15. Working Towards Explicit Modelling: Experiences of a New Teacher Educator

    ERIC Educational Resources Information Center

    White, Elizabeth

    2011-01-01

    As a new teacher educator of beginner teachers on the Graduate Teacher Programme in a large School of Education in a UK university, I have reflected on how I have been able to develop the effectiveness of modelling good professional practice to student-teachers. In this paper I will present ways in which I have made modelling more explicit, how…

  16. The Role of Explicit Need Strength for Emotions during Learning

    ERIC Educational Resources Information Center

    Flunger, Barbara; Pretsch, Johanna; Schmitt, Manfred; Ludwig, Peter

    2013-01-01

    According to self-determination theory, the satisfaction of the basic needs for autonomy, competence, and relatedness influences achievement emotions and situational interest. The present study investigated whether domain-specific explicit need strength moderated the impact of need satisfaction/dissatisfaction on the outcomes achievement emotions…

  17. Explicit Integration of Extremely Stiff Reaction Networks: Asymptotic Methods

    SciTech Connect

    Guidry, Mike W; Budiardja, R.; Feger, E.; Billings, J. J.; Hix, William Raphael; Messer, O.E.B.; Roche, K. J.; McMahon, E.; He, M.

    2013-01-01

    We show that, even for extremely stiff systems, explicit integration may compete in both accuracy and speed with implicit methods if algebraic methods are used to stabilize the numerical integration. The stabilizing algebra differs for systems well removed from equilibrium and those near equilibrium. This paper introduces a quantitative distinction between these two regimes and addresses the former case in depth, presenting explicit asymptotic methods appropriate when the system is extremely stiff but only weakly equilibrated. A second paper [1] examines quasi-steady-state methods as an alternative to asymptotic methods in systems well away from equilibrium and a third paper [2] extends these methods to equilibrium conditions in extremely stiff systems using partial equilibrium methods. All three papers present systematic evidence for timesteps competitive with implicit methods. Because explicit methods can execute a timestep faster than an implicit method, our results imply that algebraically stabilized explicit algorithms may offer a means to integration of larger networks than have been feasible previously in various disciplines.

  18. Explicit versus Implicit Questioning: Inviting All Children to Think Mathematically

    ERIC Educational Resources Information Center

    Parks, Amy Noelle

    2010-01-01

    Background/Context: Open-ended, or implicit, questioning has been described as central to reform teaching in mathematics. However, concerns about equity have caused some researchers to question whether this kind of teaching is productive for all children. Purpose: This study explores the role that implicit and explicit questions played in…

  19. An Explicitly Correlated Wavelet Method for the Electronic Schroedinger Equation

    SciTech Connect

    Bachmayr, Markus

    2010-09-30

    A discretization for an explicitly correlated formulation of the electronic Schroedinger equation based on hyperbolic wavelets and exponential sum approximations of potentials is described, covering mathematical results as well as algorithmic realization, and discussing in particular the potential of methods of this type for parallel computing.

  20. An Explicit Formula for the Berezin Star Product

    NASA Astrophysics Data System (ADS)

    Xu, Hao

    2012-09-01

    We prove an explicit formula of the Berezin star product on Kähler manifolds. The formula is expressed as a summation over certain strongly connected digraphs. The proof relies on a combinatorial interpretation of Engliš' work on the asymptotic expansion of the Laplace integral.

  1. Qualitative Differences between Implicit and Explicit Sequence Learning

    ERIC Educational Resources Information Center

    Jimenez, Luis; Vaquero, Joaquin M. M.; Lupianez, Juan

    2006-01-01

    Four experiments investigate the differences between implicit and explicit sequence learning concerning their resilience to structural and superficial task changes. A superficial change that embedded the SRT task in the context of a selection task, while maintaining the sequence, did selectively hinder the expression of implicit learning. In…

  2. Effect of explicit dimensional instruction on speech category learning.

    PubMed

    Chandrasekaran, Bharath; Yi, Han-Gyol; Smayda, Kirsten E; Maddox, W Todd

    2016-02-01

    Learning nonnative speech categories is often considered a challenging task in adulthood. This difficulty is driven by cross-language differences in weighting critical auditory dimensions that differentiate speech categories. For example, previous studies have shown that differentiating Mandarin tonal categories requires attending to dimensions related to pitch height and direction. Relative to native speakers of Mandarin, the pitch direction dimension is underweighted by native English speakers. In the current study, we examined the effect of explicit instructions (dimension instruction) on native English speakers' Mandarin tone category learning within the framework of a dual-learning systems (DLS) model. This model predicts that successful speech category learning is initially mediated by an explicit, reflective learning system that frequently utilizes unidimensional rules, with an eventual switch to a more implicit, reflexive learning system that utilizes multidimensional rules. Participants were explicitly instructed to focus and/or ignore the pitch height dimension, the pitch direction dimension, or were given no explicit prime. Our results show that instruction instructing participants to focus on pitch direction, and instruction diverting attention away from pitch height, resulted in enhanced tone categorization. Computational modeling of participant responses suggested that instruction related to pitch direction led to faster and more frequent use of multidimensional reflexive strategies and enhanced perceptual selectivity along the previously underweighted pitch direction dimension.

  3. Optimizing Language Instruction: Matters of Explicitness, Practice, and Cue Learning

    ERIC Educational Resources Information Center

    Stafford, Catherine A.; Bowden, Harriet Wood; Sanz, Cristina

    2012-01-01

    Input exposure is essential for nonprimary language learning, but the importance of explicit instruction and corrective feedback continues to be debated. If instruction is required, how might it be optimized in terms of its nature and timing? In this study, 65 Spanish-English bilinguals were introduced to Latin through an interactive computer…

  4. Attention to Explicit and Implicit Contrast in Verb Learning

    ERIC Educational Resources Information Center

    Childers, Jane B.; Hirshkowitz, Amy; Benavides, Kristin

    2014-01-01

    Contrast information could be useful for verb learning, but few studies have examined children's ability to use this type of information. Contrast may be useful when children are told explicitly that different verbs apply, or when they hear two different verbs in a single context. Three studies examine children's attention to different types of…

  5. Explicit Constructivism: A Missing Link in Ineffective Lectures?

    ERIC Educational Resources Information Center

    Prakash, E. S.

    2010-01-01

    This study tested the possibility that interactive lectures explicitly based on activating learners' prior knowledge and driven by a series of logical questions might enhance the effectiveness of lectures. A class of 54 students doing the respiratory system course in the second year of the Bachelor of Medicine and Bachelor of Surgery program in my…

  6. A Framework for Explicit Vocabulary Instruction with English Language Learners

    ERIC Educational Resources Information Center

    Nisbet, Deanna L.; Tindall, Evie R.

    2015-01-01

    Academic vocabulary development is critical to the success of all learners--particularly English language learners (ELLs). This article presents a framework for integrating explicit academic vocabulary instruction for ELLs into middle school classrooms. The framework embodies five research-based principles and serves as a vehicle for structuring…

  7. Implicit and Explicit Learning in Young Adults with Mental Retardation.

    ERIC Educational Resources Information Center

    Atwell, Julie A.; Conners, Frances A.; Merrill, Edward C.

    2003-01-01

    Young adults with (n=34) and without (n=41) mental retardation completed a sequence-learning and identification task. For some, sequences were constructed following an artificial grammar. Explicit learning was determined by ability to learn and identify random sequences, implicit learning by the tendency to identify incorrectly new grammatical…

  8. Explicit- and Implicit Bullying Attitudes in Relation to Bullying Behavior

    ERIC Educational Resources Information Center

    van Goethem, Anne A. J.; Scholte, Ron H. J.; Wiers, Reinout W.

    2010-01-01

    The main aim of this study was to examine whether an assessment of implicit bullying attitudes could add to the prediction of bullying behavior after controlling for explicit bullying attitudes. Primary school children (112 boys and 125 girls, M age = 11 years, 5 months) completed two newly developed measures of implicit bullying attitudes (a…

  9. Implicit and Explicit Learning in Individuals with Agrammatic Aphasia

    ERIC Educational Resources Information Center

    Schuchard, Julia; Thompson, Cynthia K.

    2014-01-01

    Implicit learning is a process of acquiring knowledge that occurs without conscious awareness of learning, whereas explicit learning involves the use of overt strategies. To date, research related to implicit learning following stroke has been largely restricted to the motor domain and has rarely addressed implications for language. The present…

  10. Implicit and Explicit Attitudes Toward Sex and Romance in Asexuals.

    PubMed

    Bulmer, Maria; Izuma, Keise

    2017-03-31

    Despite the recent surge of interest in sexuality, asexuality has remained relatively underresearched. Distinct from abstinence or chastity, asexuality refers to a lack of sexual attraction toward others. Past research suggests asexuals have negative attitudes toward sex, though no research has examined implicit attitudes. While preliminary evidence suggests that many asexuals are interested in engaging in romantic relationships, these attitudes have yet to be examined thoroughly, implicitly, or compared with a control group. This study investigated explicit and implicit attitudes toward sex and romance in a group of asexuals (N = 18, age M = 21.11) and a group of controls (N = 27, age M = 21.81), using the Asexuality Identification Scale (AIS), the Triangular Love Scale (TLS), semantic differentials, an Implicit Association Task (IAT), and two Single Category IATs. It was found that asexuals exhibited more negative explicit and implicit attitudes toward sex, as well as more negative explicit attitudes toward romance, relative to controls. There was no significant difference between groups on implicit romantic attitudes. Moreover, aromantic asexuals demonstrated significantly more negative explicit attitudes toward romance than romantic asexuals, though there was no significant difference between groups on implicit measures. Explanations and implications of these findings are discussed.

  11. Resolving ambiguities of MVPA using explicit models of representation

    PubMed Central

    Naselaris, Thomas; Kay, Kendrick N.

    2015-01-01

    We advocate a shift in emphasis within cognitive neuroscience from multivariate pattern analysis (MVPA) to the design and testing of explicit models of neural representation. With such models it becomes possible to identify the specific representations encoded in patterns of brain activity and to map them across the brain. PMID:26412094

  12. Revisiting the Role of Explicit Genre Instruction in the Classroom

    ERIC Educational Resources Information Center

    Frankel, Katherine K.

    2013-01-01

    At the end of the twentieth century, genre theorists and practitioners debated the possibility of explicitly teaching genres in classrooms. Though the debate is decades old, it continues to be relevant to contemporary discussions about literacy instruction because it addresses questions about how to provide all students with access to genres of…

  13. Explicit versus implicit social cognition testing in autism spectrum disorder.

    PubMed

    Callenmark, Björn; Kjellin, Lars; Rönnqvist, Louise; Bölte, Sven

    2014-08-01

    Although autism spectrum disorder is defined by reciprocal social-communication impairments, several studies have found no evidence for altered social cognition test performance. This study examined explicit (i.e. prompted) and implicit (i.e. spontaneous) variants of social cognition testing in autism spectrum disorder. A sample of 19 adolescents with autism spectrum disorder and 19 carefully matched typically developing controls completed the Dewey Story Test. 'Explicit' (multiple-choice answering format) and 'implicit' (free interview) measures of social cognition were obtained. Autism spectrum disorder participants did not differ from controls regarding explicit social cognition performance. However, the autism spectrum disorder group performed more poorly than controls on implicit social cognition performance in terms of spontaneous perspective taking and social awareness. Findings suggest that social cognition alterations in autism spectrum disorder are primarily implicit in nature and that an apparent absence of social cognition difficulties on certain tests using rather explicit testing formats does not necessarily mean social cognition typicality in autism spectrum disorder.

  14. Presenting Lexical Bundles for Explicit Noticing with Schematic Linguistic Representation

    ERIC Educational Resources Information Center

    Thomson, Haidee Elizabeth

    2016-01-01

    Lexical bundles are essential for fluency, but their incompleteness is a stumbling block for learners. In this study, two presentation methods to increase awareness of lexical bundles through explicit noticing are explored and compared with incidental exposure. The three conditions in this study were as follows: noticing with schematic linguistic…

  15. Revising Geology Labs To Explicitly Use the Scientific Method.

    ERIC Educational Resources Information Center

    Hannula, Kimberly A.

    2003-01-01

    Proposes that content- or skill-based labs can be revised to explicitly involve the scientific method by asking students to propose hypotheses before making observations. Students' self-assessment showed they felt that they learned a great deal from this style of labs and found the labs to be fun; however, students felt that they learned little…

  16. The Order of Explicit Information in Processing Instruction

    ERIC Educational Resources Information Center

    McNulty Diaz, Erin

    2017-01-01

    The two main components of Processing Instruction (PI) are Explicit Information (EI) and Structured Input (SI). Most researchers have concluded that the SI is more responsible for learner gains than the EI (Benati, 2004a, 2004b; VanPatten & Oikennon, 1996; Wong, 2004). However, some researchers have found that EI does significantly impact…

  17. "See Translation": Explicit and Implicit Language Policies on Facebook

    ERIC Educational Resources Information Center

    Hendus, Ulrike

    2015-01-01

    The currently tested "See Translation" button can be considered an expression of Facebook's explicit language policy. It offers the users fast and easy translations of others' status updates and can therefore be seen as diminishing language barriers and reducing the need for a lingua franca in polylingual networks, thus enhancing…

  18. Are Explicit Apologies Proportional to the Offenses They Address?

    ERIC Educational Resources Information Center

    Heritage, John; Raymond, Chase Wesley

    2016-01-01

    We consider here Goffman's proposal of proportionality between virtual offenses and remedial actions, based on the examination of 102 cases of explicit apologies. To this end, we offer a typology of the primary apology formats within the dataset, together with a broad categorization of the types of virtual offenses to which these apologies are…

  19. Measuring Implicit and Explicit Attitudes toward Foreign-Accented Speech

    ERIC Educational Resources Information Center

    Pantos, Andrew J.

    2010-01-01

    The purpose of this research was to investigate the nature of listeners' attitudes toward foreign-accented speech and the manner in which those attitudes are formed. This study measured 165 participants' implicit and explicit attitudes toward US- and foreign-accented audio stimuli. Implicit attitudes were measured with an audio Implicit…

  20. Explicit-Implicit Distinction: A Review of Related Literature

    ERIC Educational Resources Information Center

    Jarrah, Marwan A.

    2016-01-01

    This paper sketches out the main views of the major pragmatic approaches (i.e., Grice's theory of conversation, Relevance Theory, and Neo-Gricean pragmatic theory) on explicit-implicit distinction. It makes clear how this distinction has been differently drawn for utterance interpretation. Additionally, it highlights several corresponding problems…

  1. Implicit and Explicit Recasts in L2 Oral French Interaction

    ERIC Educational Resources Information Center

    Erlam, Rosemary; Loewen, Shawn

    2010-01-01

    This laboratory-based study of second- and third-year American university students learning French examines the effectiveness of implicit and explicit corrective feedback on noun-adjective agreement errors. The treatment consisted of one hour of interactive tasks. Implicit feedback was operationalized as a single recast with interrogative…

  2. Making the Tacit Explicit: Children's Strategies for Classroom Writing

    ERIC Educational Resources Information Center

    Silby, Alison; Watts, Mike

    2015-01-01

    A key highlight of this study is generating evidence of children "making aware the unaware", making tacit knowledge explicit. The research explores the levels of awareness in thinking used by eight 7-8 year-old children when engaged in school-based genre writing tasks. The focus is on analysing children's awareness of their thought…

  3. The importance of explicitly mapping instructional analogies in science education

    NASA Astrophysics Data System (ADS)

    Asay, Loretta Johnson

    Analogies are ubiquitous during instruction in science classrooms, yet research about the effectiveness of using analogies has produced mixed results. An aspect seldom studied is a model of instruction when using analogies. The few existing models for instruction with analogies have not often been examined quantitatively. The Teaching With Analogies (TWA) model (Glynn, 1991) is one of the models frequently cited in the variety of research about analogies. The TWA model outlines steps for instruction, including the step of explicitly mapping the features of the source to the target. An experimental study was conducted to examine the effects of explicitly mapping the features of the source and target in an analogy during computer-based instruction about electrical circuits. Explicit mapping was compared to no mapping and to a control with no analogy. Participants were ninth- and tenth-grade biology students who were each randomly assigned to one of three conditions (no analogy module, analogy module, or explicitly mapped analogy module) for computer-based instruction. Subjects took a pre-test before the instruction, which was used to assign them to a level of previous knowledge about electrical circuits for analysis of any differential effects. After the instruction modules, students took a post-test about electrical circuits. Two weeks later, they took a delayed post-test. No advantage was found for explicitly mapping the analogy. Learning patterns were the same, regardless of the type of instruction. Those who knew the least about electrical circuits, based on the pre-test, made the most gains. After the two-week delay, this group maintained the largest amount of their gain. Implications exist for science education classrooms, as analogy use should be based on research about effective practices. Further studies are suggested to foster the building of research-based models for classroom instruction with analogies.

  4. Explicit and implicit self-evaluations in social anxiety disorder.

    PubMed

    Gilboa-Schechtman, Eva; Keshet, Hadar; Livne, Tamar; Berger, Uri; Zabag, Reut; Hermesh, Haggai; Marom, Sofi

    2017-04-01

    Cognitive models of social anxiety disorder (SAD) emphasize the role of explicit and implicit self-evaluations (SEs) in the etiology and maintenance of this condition. Whereas individuals with SAD consistently report lower explicit SEs as compared with nonanxious individuals, findings concerning implicit SEs are mixed. To gain a more nuanced understanding of the nature of SEs in SAD, we examined explicit and implicit SEs in two significant interpersonal domains: social rank and affiliation. Consistent with cognitive theorizing, we predicted that, compared to nonclinical controls (NCCs), individuals with SAD would exhibit lower explicit and implicit SEs in both domains. Guided by evolutionary theories we also predicted that the differences in SEs between the groups would be greater in the social rank, as compared to the affiliation, domain. Individuals diagnosed with SAD (n = 38) and NCCs) n = 40) performed two variants of the Self Implicit Association Test: one concerning social rank, and the other concerning affiliation. They also rated themselves on social-rank and affiliation traits. We found that, as compared to NCCs, individuals with SAD exhibited lower social-rank and affiliation SEs. Moreover, differences between the groups in social-rank SEs were greater than in affiliation SEs. Importantly, this pattern was evident in implicit SEs, as much as in explicit SEs. Our findings dovetail with evolutionary accounts highlighting the centrality of the social-rank system in SAD, and refine central tenets of cognitive theories of SAD. A multidomain, multimethod approach to the understanding of the self may broaden our conceptualization of SAD and related disorders. (PsycINFO Database Record

  5. DFT solvation studies of carbohydrates: implicit and explicit solvation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Solvents play a role in carbohydrate structure. Therefore, it is important to include solvation effects in calculations to allow a more realistic comparison with experimental data. A possible way to include solvation effects is to use implicit solvation models such as COSMO and PCM. Another avenu...

  6. Mechanisms of solute rejection in solvent resistant nanofiltration: the effect of solvent on solute rejection.

    PubMed

    Darvishmanesh, Siavash; Degrève, Jan; Van der Bruggen, Bart

    2010-10-28

    The separation performance of solvent resistant nanofiltration (SRNF) membranes was studied in a systematic way to elucidate the complex mechanisms involved in rejection of solutes. Rejection of three dyes (Sudan II, Sudan Black, Sudan 408) from common organic solvents (methanol, ethanol, acetone, methyl ethyl ketone, toluene and n-hexane) through a polyimide based SRNF membrane, STARMEM™122, was studied. It was found that the rejection of the STARMEM™122 membrane was lower than that indicated by the manufacturer. The experimental observations for Sudan II were not promising for the rejection study as they were lower than expected. Sudan Black and Sudan 408, which are larger solutes than Sudan II, provided more interesting insights. The effects of the solvent on the membrane and solute were studied separately. A higher permeation rate of ketones and alcohols was observed, while permeabilities of non-polar solvents were low which shows that this membrane shows higher affinity toward semi-polar solvents (alcohols, ketones). The effect of the solvent on the solute's rejection, based on the results for Sudan Black and Sudan 408, was studied for solvents in the same chemical groups, since the membrane showed a similar separation performance for solvents with similar functional groups (e.g. alcohols). The effect of solvent on solute molecular size was investigated by using simulation with Molecular Dynamics. It was shown that the effective size of a molecule is dependent on the solvent due to solvation and hydration of the solute by the solvent. The size of the solute in the solvent belonging to a similar family was studied separately. It was clear that the rejection was influenced by molecular size of the solute in the same group of solvents. A surprising negative rejection of solutes was achieved for n-hexane. Although solutes in n-hexane have higher volume compared to those in other solvents, the affinity between the solute and membrane increases the solute

  7. REMEDIATION OF CONTAMINATED SOILS BY SOLVENT FLUSHING

    EPA Science Inventory

    Solvent flushing is a potential technique for remediating a waste disposal/spill site contaminated with organic chemicals. This technique involves the injection of a solvent mixture (e.g., water plus alcohols) that enhances contaminant solubility, reduces the retardation factor, ...

  8. Coal mining with a liquid solvent

    NASA Technical Reports Server (NTRS)

    Lawson, D. D.; Miller, C. G.

    1979-01-01

    Study suggests carbonated water can dissolve or suspend coal and carry it to surface. Mixture of carbon dioxide and water may be coal solvent that will make unmanned mining reality. When used with proposed process monitoring coal solubility with conventional strain gage, solvent is basis for rapid cost effective extraction of coal from underground seams.

  9. Remediating pesticide contaminated soils using solvent extraction

    SciTech Connect

    Sahle-Demessie, E.; Meckes, M.C.; Richardson, T.L.

    1996-12-31

    Bench-scale solvent extraction studies were performed on soil samples obtained from a Superfund site contaminated with high levels of p,p{prime}-DDT, p,p{prime}-DDE and toxaphene. The effectiveness of the solvent extraction process was assessed using methanol and 2-propanol as solvents over a wide range of operating conditions. It was demonstrated that a six-stage methanol extraction using a solvent-to-soil ratio of 1.6 can decrease pesticide levels in the soil by more than 99% and reduce the volume of material requiring further treatment by 25 times or more. The high solubility of the pesticides in methanol resulted in rapid extraction rates, with the system reaching quasi-equilibrium state in 30 minutes. The extraction efficiency was influenced by the number of extraction stages, the solvent-to-soil ratio, and the soil moisture content. Various methods were investigated to regenerate and recycle the solvent. Evaporation and solvent stripping are low cost and reliable methods for removing high pesticide concentrations from the solvent. For low concentrations, GAC adsorption may be used. Precipitating and filtering pesticides by adding water to the methanol/pesticide solution was not successful when tested with soil extracts. 26 refs., 10 figs., 6 tabs.

  10. Cytotoxic effects of gutta-percha solvents.

    PubMed

    Barbosa, S V; Burkard, D H; Spångberg, L S

    1994-01-01

    Cytotoxicity of commonly used gutta-percha solvents was evaluated. Gutta-percha dissolved by chloroform, halothane, or turpentine was evaluated with the radiochromium release method using L929 mouse fibroblast cells. All solvents were toxic. Turpentine was most toxic followed by halothane and chloroform, which caused similar levels of cell injury.

  11. Evaluation of Gutta-percha solvents.

    PubMed

    Kaplowitz, G J

    1990-11-01

    Five solvents (rectified white turpentine, oil of melaleuca, eucalyptol, white pine oil, and pine needle oil) were compared with chloroform for their ability to dissolve gutta-percha. All solvents dissolved at least 50% of the gutta-percha in 15 min at 37 degrees C with chloroform and rectified white turpentine dissolving the gutta-percha completely.

  12. SOLVENT DESIGN UNDER VARYING ENVIRONMENTAL REQUIREMENTS

    EPA Science Inventory

    There is currently a great need to replace many solvents that are commonly used by industry and the public, but whose continued use entails a number of human health and environmental risks. One issue hampering solvent replacement is the general thought that replacement, particul...

  13. Green chemicals: Searching for cleaner solvents

    SciTech Connect

    Lucas, A.

    1994-10-05

    While increased pressure from EPA has solvents producers scrambling to find greener alternatives, many say the cost effectiveness and performance characteristics of traditional technologies are such that they will not disappear quickly. Though a variety of alternative {open_quotes}green{close_quotes} solvents have been developed and commercialized, better means of solvent recovery have also come along, ensuring continued use of many organic solvents. The 1990 Clean Air Act (CAA), designed to eliminate volatile organic compounds (VOCs), ozone depleters, and other hazardous air pollutants (HAPs), has put limits on many organic solvents. Those most under fire are chlorinated solvents, such as methylene chloride, 1,1,1 trichloroethylene (methyl chloroform), and chlorofluorocarbon (CFC)-113. Producers have been developing a variety of lower VOC solvents to replace those being phased out or regulated. Among those likely to experience most growth are aliphatic hydrocarbons to replace chlorinated solvents in cleaning applications. Growth is also expected for alcohols, esters, and glycol ethers for other end-use applications.

  14. REMEDIATING PESTICIDE CONTAMINATED SOILS USING SOLVENT EXTRACTION

    EPA Science Inventory

    Bench-scale solvent extraction studies were performed on soil samples obtained from a Superfund site contaminated with high levels of p,p'-DDT, p,p'-DDD,, p,p'-DDE and toxaphene. The effectiveness of the solvent extraction process was assessed using methanol and 2-propanol as sol...

  15. A spreadsheet algorithm for stagewise solvent extraction

    SciTech Connect

    Leonard, R.A.; Regalbuto, M.C.

    1993-01-01

    Part of the novelty is the way in which the problem is organized in the spreadsheet. In addition, to facilitate spreadsheet setup, a new calculational procedure has been developed. The resulting Spreadsheet Algorithm for Stagewise Solvent Extraction (SASSE) can be used with either IBM or Macintosh personal computers as a simple yet powerful tool for analyzing solvent extraction flowsheets.

  16. EXPERIENCES IN DESIGNING SOLVENTS FOR THE ENVIRONMENT

    EPA Science Inventory

    Solvents used throughout industry are chosen to meet specific technological requirements such as solute solubility, cleaning and degreasing, or being a medium for paints and coatings. With the increasing awareness of the human health effects and environmental tisks of solvent use...

  17. EXPERIENCES IN DESIGNING SOLVENTS FOR THE ENVIRONMENT

    EPA Science Inventory

    Solvents used throughout industry are chosen to meet specific technological requirements such as solute solubility, cleaning and degreasing, or being a medium for paints and coatings. With the increasing awareness of the human health effects and environmental risks of solvent use...

  18. SOLVENT-FREE ORGANIC SYNTHESES USING MICROWAVES

    EPA Science Inventory

    The latest results on microwave-expedited solvent-free approach as applied to the assembly of organic molecules will be presented. The salient features of this expeditious methodology such as solvent conservation and ease of manipulation etc. will be described in the context of r...

  19. Solvent effect in the Walden inversion reactions

    NASA Astrophysics Data System (ADS)

    Jaume, J.; Lluch, J. M.; Oliva, A.; Bertrán, J.

    1984-04-01

    The solvent effect on the fluoride exchange reaction has been studied by means of ab initio calculations using the 3-21G basis set. It is shown that the motion of the solvent molecules is an important part of the reaction coordinate.

  20. Improved Supercritical-Solvent Extraction of Coal

    NASA Technical Reports Server (NTRS)

    Compton, L.

    1982-01-01

    Raw coal upgraded by supercritical-solvent extraction system that uses two materials instead of one. System achieved extraction yields of 20 to 49 weight percent. Single-solvent yields are about 25 weight percent. Experimental results show extraction yields may be timedependent. Observed decreases in weight of coal agreed well with increases in ash content of residue.

  1. Supercritical-Multiple-Solvent Extraction From Coal

    NASA Technical Reports Server (NTRS)

    Corcoran, W.; Fong, W.; Pichaichanarong, P.; Chan, P.; Lawson, D.

    1983-01-01

    Large and small molecules dissolve different constituents. Experimental apparatus used to test supercritical extraction of hydrogen rich compounds from coal in various organic solvents. In decreasing order of importance, relevant process parameters were found to be temperature, solvent type, pressure, and residence time.

  2. Electrostatics of proteins in dielectric solvent continua. I. Newton's third law marries qE forces

    NASA Astrophysics Data System (ADS)

    Stork, Martina; Tavan, Paul

    2007-04-01

    The authors reformulate and revise an electrostatic theory treating proteins surrounded by dielectric solvent continua [B. Egwolf and P. Tavan, J. Chem. Phys. 118, 2039 (2003)] to make the resulting reaction field (RF) forces compatible with Newton's third law. Such a compatibility is required for their use in molecular dynamics (MD) simulations, in which the proteins are modeled by all-atom molecular mechanics force fields. According to the original theory the RF forces, which are due to the electric field generated by the solvent polarization and act on the partial charges of a protein, i.e., the so-called qE forces, can be quite accurately computed from Gaussian RF dipoles localized at the protein atoms. Using a slightly different approximation scheme also the RF energies of given protein configurations are obtained. However, because the qE forces do not account for the dielectric boundary pressure exerted by the solvent continuum on the protein, they do not obey the principle that actio equals reactio as required by Newton's third law. Therefore, their use in MD simulations is severely hampered. An analysis of the original theory has led the authors now to a reformulation removing the main difficulties. By considering the RF energy, which represents the dominant electrostatic contribution to the free energy of solvation for a given protein configuration, they show that its negative configurational gradient yields mean RF forces obeying the reactio principle. Because the evaluation of these mean forces is computationally much more demanding than that of the qE forces, they derive a suggestion how the qE forces can be modified to obey Newton's third law. Various properties of the thus established theory, particularly issues of accuracy and of computational efficiency, are discussed. A sample application to a MD simulation of a peptide in solution is described in the following paper [M. Stork and P. Tavan, J. Chem. Phys., 126, 165106 (2007).

  3. Electrostatics of proteins in dielectric solvent continua. I. Newton's third law marries qE forces.

    PubMed

    Stork, Martina; Tavan, Paul

    2007-04-28

    The authors reformulate and revise an electrostatic theory treating proteins surrounded by dielectric solvent continua [B. Egwolf and P. Tavan, J. Chem. Phys. 118, 2039 (2003)] to make the resulting reaction field (RF) forces compatible with Newton's third law. Such a compatibility is required for their use in molecular dynamics (MD) simulations, in which the proteins are modeled by all-atom molecular mechanics force fields. According to the original theory the RF forces, which are due to the electric field generated by the solvent polarization and act on the partial charges of a protein, i.e., the so-called qE forces, can be quite accurately computed from Gaussian RF dipoles localized at the protein atoms. Using a slightly different approximation scheme also the RF energies of given protein configurations are obtained. However, because the qE forces do not account for the dielectric boundary pressure exerted by the solvent continuum on the protein, they do not obey the principle that actio equals reactio as required by Newton's third law. Therefore, their use in MD simulations is severely hampered. An analysis of the original theory has led the authors now to a reformulation removing the main difficulties. By considering the RF energy, which represents the dominant electrostatic contribution to the free energy of solvation for a given protein configuration, they show that its negative configurational gradient yields mean RF forces obeying the reactio principle. Because the evaluation of these mean forces is computationally much more demanding than that of the qE forces, they derive a suggestion how the qE forces can be modified to obey Newton's third law. Various properties of the thus established theory, particularly issues of accuracy and of computational efficiency, are discussed. A sample application to a MD simulation of a peptide in solution is described in the following paper [M. Stork and P. Tavan, J. Chem. Phys., 126, 165106 (2007).

  4. Parameterization of the Hamiltonian Dielectric Solvent (HADES) Reaction-Field Method for the Solvation Free Energies of Amino Acid Side-Chain Analogs.

    PubMed

    Zachmann, Martin; Mathias, Gerald; Antes, Iris

    2015-06-08

    Optimization of the Hamiltonian dielectric solvent (HADES) method for biomolecular simulations in a dielectric continuum is presented with the goal of calculating accurate absolute solvation free energies while retaining the model's accuracy in predicting conformational free-energy differences. The solvation free energies of neutral and polar amino acid side-chain analogs calculated by using HADES, which may optionally include nonpolar contributions, were optimized against experimental data to reach a chemical accuracy of about 0.5 kcal mol(-1). The new parameters were evaluated for charged side-chain analogs. The HADES results were compared with explicit-solvent, generalized Born, Poisson-Boltzmann, and QM-based methods. The potentials of mean force (PMFs) between pairs of side-chain analogs obtained by using HADES and explicit-solvent simulations were used to evaluate the effects of the improved parameters optimized for solvation free energies on intermolecular potentials.

  5. Thermoplastic composite matrices with improved solvent resistance

    NASA Technical Reports Server (NTRS)

    Hergenrother, P. M.; Jensen, B. J.; Havens, S. J.

    1984-01-01

    In order to improve solvent resistance of aromatic thermoplastic polymers, ethynyl-terminated aromatic sulfone polymers (ETS), sulfone/ester polymers (SEPE) containing pendent ethynyl groups, and phenoxy resin containing pendent ethynyl groups are synthesized. Cured polysulfones and phenoxy resins containing ethynyl groups on the ends or pendent on the molecules exhibited systematic behavior in solvent resistance, film flexibility, and toughness as a function of crosslink density. The film and composite properties of a cured solvent-resistant ETS were better than those of a commercially available solvent sensitive polysulfone. The study was part of a NASA program to better understand the trade-offs between solvent resistance, processability and mechanical properties which may be useful in designing composite structures for aerospace vehicles.

  6. METHOD FOR SOLVENT-ISOSTATIC PRESSING

    DOEpatents

    Archibald, P.B.

    1962-09-18

    This invention provides a method for producing densely compacted bodies having relatively large dimensions. The method comprises the addition of a small quantity of a suitable solvent to a powder which is to be compacted. The solvent- moistened powder is placed inside a flexible bag, and the bag is suspended in an isostatic press. The solvent is squeezed out of the powder by the isostatic pressure, and the resulting compacted body is recovered. The presence of the solvent markedly decreases the proportion of void space in the powder, thereby resulting in a denser, more homogeneous compact. Another effect of the solvent is that it allows the isostatic pressing operation to be conducted at substantially lower pressures than are conventionally employed. (AEC)

  7. Stabilization of Underground Solvent Storage Tanks

    SciTech Connect

    Smail, T.R.

    2003-08-15

    The Old Solvent Tanks (OST), located at the Savannah River Site (SRS) are comprised of 22 underground storage tanks that were used to store spent radioactive solvent and aqueous wastes generated from the plutonium-uranium extraction (PUREX) process. The OSTs were installed at various dates between 1955 and 1968 and used to store the spent solvents until 1974. The spent solvents stored in the OSTs were transferred out from 1976 through 1981 leaving only residual liquids and sludges that could not be pumped out.Final remediation goals include an overlying infiltration control system. If the tanks were to structurally fail, they would collapse causing potential for onsite worker exposure and release of tank contents to the environment. Therefore, as an interim action, methods for stabilizing the tanks were evaluated. This paper will discuss the systems designed to perform and monitor the grouting operation, the grouting process, and the radiological controls and wastes associated with grouting the Old Solvent Tanks.

  8. SOLVENT DISPERSION AND FLOW METER CALCULATION RESULTS

    SciTech Connect

    Nash, C.; Fondeur, F.; Peters, T.

    2013-06-21

    Savannah River National Laboratory (SRNL) found that the dispersion numbers for the six combinations of CSSX:Next Generation Solvent (NGS) “blend” and pure NGS versus salt solution, caustic wash, and strip aqueous solutions are all good. The dispersion numbers are indications of processability with centrifugal contactors. A comparison of solvent physical and thermal properties shows that the Intek™ solvent flow meter in the plant has a reading biased high versus calibrated flow when NGS is used, versus the standard CSSX solvent. The flow meter, calibrated for CSSX solvent, is predicted to read 2.8 gpm of NGS in a case where the true flow of NGS is 2.16 gpm.

  9. Assessment of solvents for cellulose dissolution.

    PubMed

    Ghasemi, Mohammad; Tsianou, Marina; Alexandridis, Paschalis

    2017-03-01

    A necessary step in the processing of biomass is the pretreatment and dissolution of cellulose. A good solvent for cellulose involves high diffusivity, aggressiveness in decrystallization, and capability of disassociating the cellulose chains. However, it is not clear which of these factors and under what conditions should be improved in order to obtain a more effective solvent. To this end, a newly-developed phenomenological model has been applied to assess the controlling mechanism of cellulose dissolution. Among the findings, the cellulose fibers remain crystalline almost to the end of the dissolution process for decrystallization-controlled kinetics. In such solvents, decreasing the fiber crystallinity, e.g., via pretreatment, would result in a considerable increase in the dissolution rate. Such insights improve the understanding of cellulose dissolution and facilitate the selection of more efficient solvents and processing conditions for biomass. Specific examples of solvents are provided where dissolution is limited due to decrystallization or disentanglement.

  10. Toxic hepatitis in occupational exposure to solvents

    PubMed Central

    Malaguarnera, Giulia; Cataudella, Emanuela; Giordano, Maria; Nunnari, Giuseppe; Chisari, Giuseppe; Malaguarnera, Mariano

    2012-01-01

    The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. Work activities with hepatotoxins exposures are numerous and, moreover, organic solvents are used in various industrial processes. Organic solvents used in different industrial processes may be associated with hepatotoxicity. Several factors contribute to liver toxicity; among these are: species differences, nutritional condition, genetic factors, interaction with medications in use, alcohol abuse and interaction, and age. This review addresses the mechanisms of hepatotoxicity. The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. The health impact of exposure to solvents in the workplace remains an interesting and worrying question for professional health work. PMID:22719183

  11. PARIS II: Computer Aided Solvent Design for Pollution Prevention

    EPA Science Inventory

    This product is a summary of U.S. EPA researchers' work developing the solvent substitution software tool PARIS II (Program for Assisting the Replacement of Industrial Solvents, version 2.0). PARIS II finds less toxic solvents or solvent mixtures to replace more toxic solvents co...

  12. Water Solvent Effect on Theoretical Evaluation of (1)H NMR Chemical Shifts: o-Methyl-Inositol Isomer.

    PubMed

    Dos Santos, Hélio F; Chagas, Marcelo A; De Souza, Leonardo A; Rocha, Willian R; De Almeida, Mauro V; Anconi, Cleber P A; De Almeida, Wagner B

    2017-04-13

    In this paper, density functional theory calculations of nuclear magnetic resonance (NMR) chemical shifts for l-quebrachitol isomer, previously studied in our group, are reported with the aim of investigating in more detail the water solvent effect on the prediction of (1)H NMR spectra. In order to include explicit water molecules, 20 water-l-quebrachitol configurations obtained from Monte Carlo simulation were selected to perform geometry optimizations using the effective fragment potential method encompassing 60 water molecules around the solute. The solvated solute optimized geometries were then used in B3LYP/6-311+G(2d,p) NMR calculations with PCM-water. The inclusion of explicit solvent in the B3LYP NMR calculations resulted in large changes in the (1)H NMR profiles. We found a remarkable improvement in the agreement with experimental NMR profiles when the explicit hydrated l-quebrachitol structure is used in B3LYP (1)H NMR calculations, yielding a mean absolute error (MAE) of only 0.07 ppm, much lower than reported previously for the gas phase optimized structure (MAE = 0.11 ppm). In addition, a very improved match between theoretical and experimental (1)H NMR spectrum measured in D2O was achieved with the new hydrated optimized l-quebrachitol structure, showing that a fine-tuning of the theoretical NMR spectra can be accomplished once solvent effects are properly considered.

  13. ACCELERATED SOLVENT EXTRACTION COMBINED WITH ...

    EPA Pesticide Factsheets

    A research project was initiated to address a recurring problem of elevated detection limits above required risk-based concentrations for the determination of semivolatile organic compounds in high moisture content solid samples. This project was initiated, in cooperation with the EPA Region 1 Laboratory, under the Regional Methods Program administered through the ORD Office of Science Policy. The aim of the project was to develop an approach for the rapid removal of water in high moisture content solids (e.g., wetland sediments) in preparation for analysis via Method 8270. Alternative methods for water removal have been investigated to enhance compound solid concentrations and improve extraction efficiency, with the use of pressure filtration providing a high-throughput alternative for removal of the majority of free water in sediments and sludges. In order to eliminate problems with phase separation during extraction of solids using Accelerated Solvent Extraction, a variation of a water-isopropanol extraction method developed at the USGS National Water Quality Laboratory in Denver, CO is being employed. The concentrations of target compounds in water-isopropanol extraction fluids are subsequently analyzed using an automated Solid Phase Extraction (SPE)-GC/MS method developed in our laboratory. The coupled approaches for dewatering, extraction, and target compound identification-quantitation provide a useful alternative to enhance sample throughput for Me

  14. Implicit versus explicit momentum relaxation time solution for semiconductor nanowires

    SciTech Connect

    Marin, E. G. Ruiz, F. G. Godoy, A. Tienda-Luna, I. M.; Gámiz, F.

    2015-07-14

    We discuss the necessity of the exact implicit Momentum Relaxation Time (MRT) solution of the Boltzmann transport equation in order to achieve reliable carrier mobility results in semiconductor nanowires. Firstly, the implicit solution for a 1D electron gas with a isotropic bandstructure is presented resulting in the formulation of a simple matrix system. Using this solution as a reference, the explicit approach is demonstrated to be inaccurate for the calculation of inelastic anisotropic mechanisms such as polar optical phonons, characteristic of III-V materials. Its validity for elastic and isotropic mechanisms is also evaluated. Finally, the implications of the MRT explicit approach inaccuracies on the total mobility of Si and III-V NWs are studied.

  15. Highly stable explicit technique for stiff reaction-transport PDEs

    SciTech Connect

    Aro, C. J., LLNL

    1996-12-01

    The numerical simulation of chemically reacting flows is a topic that has attracted a great deal of current research. At the heart of numerical reactive flow simulations are large sets of coupled, nonlinear partial differential equations (PDEs). Due to the stiffness that is usually present, explicit time differencing schemes are not used despite their inherent simplicity and efficiency on parallel and vector machines, since these schemes require prohibitively small numerical stepsizes. Implicit time differencing schemes, although possessing good stability characteristics, introduce a great deal of computational overhead necessary to solve the simultaneous algebraic system at each timestep. This paper proposes an algorithm based on a preconditioned time differencing scheme. The algorithm is explicit and permits a large stable time step. A study of the algorithm's performance on a parallel architecture is presented.

  16. Alcohol affects goal commitment by explicitly and implicitly induced myopia.

    PubMed

    Sevincer, A Timur; Oettingen, Gabriele; Lerner, Tobias

    2012-05-01

    Alcohol commits people to personally important goals even if expectations of reaching the goals are low. To illuminate this effect, we used alcohol myopia theory, stating that alcohol intoxicated people disproportionally attend to the most salient aspects of a situation and ignore peripheral aspects. When low expectations of reaching an important goal were activated students who consumed alcohol were less committed than students who consumed a placebo. We observed less commitment regardless of whether low expectations were explicitly activated in a questionnaire (Study 1) or implicitly activated through subliminal priming (Study 2). The results imply that, intoxicated people commit to goals according to what aspects of a goal are activated either explicitly or implicitly.

  17. Approximate explicit analytic solution of the Elenbaas-Heller equation

    NASA Astrophysics Data System (ADS)

    Liao, Meng-Ran; Li, Hui; Xia, Wei-Dong

    2016-08-01

    The Elenbaas-Heller equation describing the temperature field of a cylindrically symmetrical non-radiative electric arc has been solved, and approximate explicit analytic solutions are obtained. The radial distributions of the heat-flux potential and the electrical conductivity have been figured out briefly by using some special simplification techniques. The relations between both the core heat-flux potential and the electric field with the total arc current have also been given in several easy explicit formulas. Besides, the special voltage-ampere characteristic of electric arcs is explained intuitionally by a simple expression involving the Lambert W-function. The analyses also provide a preliminary estimation of the Joule heating per unit length, which has been verified in previous investigations. Helium arc is used to examine the theories, and the results agree well with the numerical computations.

  18. On explicit algebraic stress models for complex turbulent flows

    NASA Technical Reports Server (NTRS)

    Gatski, T. B.; Speziale, C. G.

    1992-01-01

    Explicit algebraic stress models that are valid for three-dimensional turbulent flows in noninertial frames are systematically derived from a hierarchy of second-order closure models. This represents a generalization of the model derived by Pope who based his analysis on the Launder, Reece, and Rodi model restricted to two-dimensional turbulent flows in an inertial frame. The relationship between the new models and traditional algebraic stress models -- as well as anistropic eddy visosity models -- is theoretically established. The need for regularization is demonstrated in an effort to explain why traditional algebraic stress models have failed in complex flows. It is also shown that these explicit algebraic stress models can shed new light on what second-order closure models predict for the equilibrium states of homogeneous turbulent flows and can serve as a useful alternative in practical computations.

  19. Toward an explicit analysis of generalization: A stimulus control interpretation

    PubMed Central

    Kirby, Kimberly C.; Bickel, Warren K.

    1988-01-01

    Producing generality of treatment effects to new settings has been a critical concern for applied behavior analysts, but a systematic and reliable means of producing generality has yet to be provided. We argue that the principles of stimulus control and reinforcement underlie the production of most generalized effects; therefore, we suggest interpreting generalization programming in terms of stimulus control. The generalization programming procedures identified by Stokes and Baer (1977) are discussed in terms of both the stimulus control tactics explicitly identified and those that may be operating but are not explicitly identified. Our interpretation clarifies the critical components of Stokes and Baer's procedures and places greater emphasis on planning for generalization as a part of training procedures. PMID:22478006

  20. The use of explicit building blocks in evolutionary computation

    NASA Astrophysics Data System (ADS)

    Sangkavichitr, Chalermsub; Chongstitvatana, Prabhas

    2016-02-01

    This paper proposes a new algorithm to identify and compose building blocks. Building blocks are interpreted as common subsequences between good individuals. The proposed algorithm can extract building blocks from a population explicitly. Explicit building blocks are identified from shared alleles among multiple chromosomes. These building blocks are stored in an archive. They are recombined to generate offspring. The additively decomposable problems and hierarchical decomposable problems are used to validate the algorithm. The results are compared with the Bayesian optimisation algorithm, the hierarchical Bayesian optimisation algorithm, and the chi-square matrix. This proposed algorithm is simple, effective, and fast. The experimental results confirm that building block identification is an important process that guides the recombination procedure to improve the solutions. In addition, the method efficiently solves hard problems.