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Sample records for explicitly solvated biomolecular

  1. Biomolecular electrostatics and solvation: a computational perspective.

    Science.gov (United States)

    Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G; Schnieders, Michael J; Marucho, Marcelo; Zhang, Jiajing; Baker, Nathan A

    2012-11-01

    An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view toward describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g. solvent structure, polarization, ion binding, and non-polar behavior) in order to provide a background to understand the different types of solvation models.

  2. Improvements to the APBS biomolecular solvation software suite.

    Science.gov (United States)

    Jurrus, Elizabeth; Engel, Dave; Star, Keith; Monson, Kyle; Brandi, Juan; Felberg, Lisa E; Brookes, David H; Wilson, Leighton; Chen, Jiahui; Liles, Karina; Chun, Minju; Li, Peter; Gohara, David W; Dolinsky, Todd; Konecny, Robert; Koes, David R; Nielsen, Jens Erik; Head-Gordon, Teresa; Geng, Weihua; Krasny, Robert; Wei, Guo-Wei; Holst, Michael J; McCammon, J Andrew; Baker, Nathan A

    2018-01-01

    The Adaptive Poisson-Boltzmann Solver (APBS) software was developed to solve the equations of continuum electrostatics for large biomolecular assemblages that have provided impact in the study of a broad range of chemical, biological, and biomedical applications. APBS addresses the three key technology challenges for understanding solvation and electrostatics in biomedical applications: accurate and efficient models for biomolecular solvation and electrostatics, robust and scalable software for applying those theories to biomolecular systems, and mechanisms for sharing and analyzing biomolecular electrostatics data in the scientific community. To address new research applications and advancing computational capabilities, we have continually updated APBS and its suite of accompanying software since its release in 2001. In this article, we discuss the models and capabilities that have recently been implemented within the APBS software package including a Poisson-Boltzmann analytical and a semi-analytical solver, an optimized boundary element solver, a geometry-based geometric flow solvation model, a graph theory-based algorithm for determining pK a values, and an improved web-based visualization tool for viewing electrostatics. © 2017 The Protein Society.

  3. Differential geometry-based solvation and electrolyte transport models for biomolecular modeling: a review

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Guowei; Baker, Nathan A.

    2016-11-11

    This chapter reviews the differential geometry-based solvation and electrolyte transport for biomolecular solvation that have been developed over the past decade. A key component of these methods is the differential geometry of surfaces theory, as applied to the solvent-solute boundary. In these approaches, the solvent-solute boundary is determined by a variational principle that determines the major physical observables of interest, for example, biomolecular surface area, enclosed volume, electrostatic potential, ion density, electron density, etc. Recently, differential geometry theory has been used to define the surfaces that separate the microscopic (solute) domains for biomolecules from the macroscopic (solvent) domains. In these approaches, the microscopic domains are modeled with atomistic or quantum mechanical descriptions, while continuum mechanics models (including fluid mechanics, elastic mechanics, and continuum electrostatics) are applied to the macroscopic domains. This multiphysics description is integrated through an energy functional formalism and the resulting Euler-Lagrange equation is employed to derive a variety of governing partial differential equations for different solvation and transport processes; e.g., the Laplace-Beltrami equation for the solvent-solute interface, Poisson or Poisson-Boltzmann equations for electrostatic potentials, the Nernst-Planck equation for ion densities, and the Kohn-Sham equation for solute electron density. Extensive validation of these models has been carried out over hundreds of molecules, including proteins and ion channels, and the experimental data have been compared in terms of solvation energies, voltage-current curves, and density distributions. We also propose a new quantum model for electrolyte transport.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Ab initio joint density-functional theory of solvated electrodes, with model and explicit solvation

    Science.gov (United States)

    Arias, Tomas

    2015-03-01

    the electrochemical context and how it is needed for realistic description of solvated electrode systems [], and how simple ``implicit'' polarized continuum methods fail radically in this context. Finally, we shall present a series of results relevant to battery, supercapacitor, and solar-fuel systems, one of which has led to a recent invention disclosure for improving battery cycle lifetimes. Supported as a part of the Energy Materials Center at Cornell, an Energy Frontier Research Center funded by DOE/BES (award de-sc0001086) and by the New York State Division of Science, Technology and Innovation (NYSTAR, award 60923).

  6. Solvation!

    Energy Technology Data Exchange (ETDEWEB)

    Adamovic, Ivana [Iowa State Univ., Ames, IA (United States)

    2004-01-01

    This dissertation consists of two closely related parts: theory development and coding of correlation effects in a model potential for solvation, and study of solvent effects on chemical reactions and processes. The effective fragment potential (EFP) method has been re-parameterized, using density functional theory (DFT), more specifically, the B3LYP functional. The DFT based EFP method includes short-range correlation effects; hence it is a first step in incorporating the treatment of correlation in the EFP solvation model. In addition, the gradient of the charge penetration term in the EFP model was derived and coded. The new method has been implemented in the electronic structure code GAMESS and is in use. Formulas for the dynamic dipole polarizability, C6 dispersion coefficient and dispersion energy were derived and coded as a part of a treatment of the dispersion interactions in the general solvation model, EFP2. Preliminary results are in good agreement with experimental and other theoretical data. The DFT based EFP (EFP1/DFT) method was used in the study of microsolvation effects on the SN2 substitution reaction, between chloride and methyl bromide. Changes in the central barrier, for several lowest lying isomers of the systems with one, two, three and four waters, were studied using second order perturbation theory (MP2), DFT and mixed quantum mechanics (QM)/(EFP1/DFT) methods. EFP1/DFT is found to reproduce QM results with high accuracy, at just a fraction of the cost. Molecular structures and potential energy surfaces for IHI- • Arn (n=1-7) were studied using the MP2 method. Experimentally observed trends in the structural arrangement of the Ar atoms were explained through the analysis of the geometrical parameters and three-dimensional MP2 molecular electrostatic potentials.

  7. An efficient hybrid explicit/implicit solvent method for biomolecular simulations.

    Science.gov (United States)

    Lee, Michael S; Salsbury, Freddie R; Olson, Mark A

    2004-12-01

    We present a new hybrid explicit/implicit solvent method for dynamics simulations of macromolecular systems. The method models explicitly the hydration of the solute by either a layer or sphere of water molecules, and the generalized Born (GB) theory is used to treat the bulk continuum solvent outside the explicit simulation volume. To reduce the computational cost, we implemented a multigrid method for evaluating the pairwise electrostatic and GB terms. It is shown that for typical ion and protein simulations our method achieves similar equilibrium and dynamical observables as the conventional particle mesh Ewald (PME) method. Simulation timings are reported, which indicate that the hybrid method is much faster than PME, primarily due to a significant reduction in the number of explicit water molecules required to model hydration effects. (c) 2004 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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.

  9. DFT molecular simulations of solvated glucose dimers: explicit vs. implicit water

    Science.gov (United States)

    The behavior of Glucose dimers in solution is investigated at the DFT level of theory via optimization and constant energy DFT molecular dynamics. The effect of the solvent on the dimer is treated two different ways: using the implicit solvation method COSMO alone to treat the bulk water behavior an...

  10. Accurate calculation of conformational free energy differences in explicit water: the confinement-solvation free energy approach.

    Science.gov (United States)

    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.

  11. Comparison of Implicit and Explicit Solvent Models for the Calculation of Solvation Free Energy in Organic Solvents.

    Science.gov (United States)

    Zhang, Jin; Zhang, Haiyang; Wu, Tao; Wang, Qi; van der Spoel, David

    2017-03-14

    Quantitative prediction of physical properties of liquids is important for many applications. Computational methods based on either explicit or implicit solvent models can be used to approximate thermodynamics properties of liquids. Here, we evaluate the predictive power of implicit solvent models for solvation free energy of organic molecules in organic solvents. We compared the results calculated with four generalized Born (GB) models (GBStill, GBHCT, GBOBCI, and GBOBCII), the Poisson-Boltzmann (PB) model, and the density-based solvent model SMD with previous solvation free energy calculations (Zhang et al. J. Chem. Inf. 2015, 55, 1192-1201) and experimental data. The comparison indicates that both PB and GB give poor agreement with explicit solvent calculations and even worse agreement with experiments (root-mean-square deviation ≈ 15 kJ/mol). The main problem seems to be the prediction of the apolar contribution, which should include the solvent entropy. The quantum mechanical-based SMD model gives significantly better agreement with experimental data than do PB or GB, but it is not as good as explicit solvent calculation results. The dielectric constant ε of the solvent is found to be a powerful predictor for the polar contribution to the free energy in implicit models; however, the Onsager relation may not hold for realistic solvent, as suggested by explicit solvent and SMD calculations. From the comparison, we also find that with an optimization of the apolar contribution, the PB model gives slightly better agreement with experiments than the SMD model, whereas the correlation between the optimized GB models and experiments remains poor. Further optimization of the apolar contribution is needed for GB models to be able to treat solvents other than water.

  12. An explicit quantum chemical method for modeling large solvation shells applied to aminocoumarin C151

    NARCIS (Netherlands)

    Neugebauer, J.; Jacob, C.R.; Wesolowski, T.A.; Baerends, E.J.

    2005-01-01

    The absorption spectra of aminocoumarin C151 in water and n-hexane solution are investigated by an explicit quantum chemical solvent model. We improved the efficiency of the frozen-density embedding scheme, as used in a former study on solvatochromism (J. Chem. Phys. 2005, 122, 094115) to describe

  13. Fragment Molecular Orbital method-based Molecular Dynamics (FMO-MD) as a simulator for chemical reactions in explicit solvation.

    Science.gov (United States)

    Komeiji, Yuto; Ishikawa, Takeshi; Mochizuki, Yuji; Yamataka, Hiroshi; Nakano, Tatsuya

    2009-01-15

    Fragment Molecular Orbital based-Molecular Dynamics (FMO-MD, Komeiji et al., Chem Phys Lett 2003, 372, 342) is an ab initio MD method suitable for large molecular systems. Here, FMO-MD was implemented to conduct full quantum simulations of chemical reactions in explicit solvation. Several FMO-MD simulations were performed for a sphere of water to find a suitable simulation protocol. It was found that annealing of the initial configuration by a classical MD brought the subsequent FMO-MD trajectory to faster stabilization, and also that use of bond constraint in the FMO-MD heating stage effectively reduced the computation time. Then, the blue moon ensemble method (Sprik and Ciccotti, J Chem Phys 1998, 109, 7737) was implemented and was tested by calculating free energy profiles of the Menschutkin reaction (H3N + CH3Cl --> +H3NCH3 + Cl-) in the presence and absence of the solvent water via FMO-MD. The obtained free energy profiles were consistent with the Hammond postulate in that stabilization of the product by the solvent, namely hydration of Cl-, shifted the transition state to the reactant-side. Based on these FMO-MD results, plans for further improvement of the method are discussed. Copyright 2008 Wiley Periodicals, Inc.

  14. Surface Protonation at the Rutile (110) Interface: Explicit Incorporation of Solvation Structure within the Refined MUSIC Model Framework

    Energy Technology Data Exchange (ETDEWEB)

    Machesky, Michael L. [Illinois State Water Survey, Champaign, IL; Predota, M. [University of South Bohemia, Czech Republic; Wesolowski, David J [ORNL

    2008-01-01

    The detailed solvation structure at the (110) surface of rutile ({alpha}-TiO{sub 2}) in contact with bulk liquid water has been obtained primarily from experimentally verified classical molecular dynamics (CMD) simulations of the ab initio-optimized surface in contact with SPC/E water. The results are used to explicitly quantify H-bonding interactions, which are then used within the refined MUSIC model framework to predict surface oxygen protonation constants. Quantum mechanical molecular dynamics (QMD) simulations in the presence of freely dissociable water molecules produced H-bond distributions around deprotonated surface oxygens very similar to those obtained by CMD with nondissociable SPC/E water, thereby confirming that the less computationally intensive CMD simulations provide accurate H-bond information. Utilizing this H-bond information within the refined MUSIC model, along with manually adjusted Ti-O surface bond lengths that are nonetheless within 0.05 {angstrom} of those obtained from static density functional theory (DFT) calculations and measured in X-ray reflectivity experiments (as well as bulk crystal values), give surface protonation constants that result in a calculated zero net proton charge pH value (pHznpc) at 25 C that agrees quantitatively with the experimentally determined value (5.4 {+-} 0.2) for a specific rutile powder dominated by the (110) crystal face. Moreover, the predicted pH{sub znpc} values agree to within 0.1 pH unit with those measured at all temperatures between 10 and 250 C. A slightly smaller manual adjustment of the DFT-derived Ti-O surface bond lengths was sufficient to bring the predicted pH{sub znpc} value of the rutile (110) surface at 25 C into quantitative agreement with the experimental value (4.8 {+-} 0.3) obtained from a polished and annealed rutile (110) single crystal surface in contact with dilute sodium nitrate solutions using second harmonic generation (SHG) intensity measurements as a function of ionic

  15. Surface protonation at the rutile (110) interface: explicit incorporation of solvation structure within the refined MUSIC model framework.

    Science.gov (United States)

    Machesky, Michael L; Predota, Milan; Wesolowski, David J; Vlcek, Lukas; Cummings, Peter T; Rosenqvist, Jörgen; Ridley, Moira K; Kubicki, James D; Bandura, Andrei V; Kumar, Nitin; Sofo, Jorge O

    2008-11-04

    The detailed solvation structure at the (110) surface of rutile (alpha-TiO2) in contact with bulk liquid water has been obtained primarily from experimentally verified classical molecular dynamics (CMD) simulations of the ab initio-optimized surface in contact with SPC/E water. The results are used to explicitly quantify H-bonding interactions, which are then used within the refined MUSIC model framework to predict surface oxygen protonation constants. Quantum mechanical molecular dynamics (QMD) simulations in the presence of freely dissociable water molecules produced H-bond distributions around deprotonated surface oxygens very similar to those obtained by CMD with nondissociable SPC/E water, thereby confirming that the less computationally intensive CMD simulations provide accurate H-bond information. Utilizing this H-bond information within the refined MUSIC model, along with manually adjusted Ti-O surface bond lengths that are nonetheless within 0.05 A of those obtained from static density functional theory (DFT) calculations and measured in X-ray reflectivity experiments (as well as bulk crystal values), give surface protonation constants that result in a calculated zero net proton charge pH value (pHznpc) at 25 degrees C that agrees quantitatively with the experimentally determined value (5.4+/-0.2) for a specific rutile powder dominated by the (110) crystal face. Moreover, the predicted pHznpc values agree to within 0.1 pH unit with those measured at all temperatures between 10 and 250 degrees C. A slightly smaller manual adjustment of the DFT-derived Ti-O surface bond lengths was sufficient to bring the predicted pHznpcvalue of the rutile (110) surface at 25 degrees C into quantitative agreement with the experimental value (4.8+/-0.3) obtained from a polished and annealed rutile (110) single crystal surface in contact with dilute sodium nitrate solutions using second harmonic generation (SHG) intensity measurements as a function of ionic strength

  16. An explicitly solvated full atomistic model of the cardiac thin filament and application on the calcium binding affinity effects from familial hypertrophic cardiomyopathy linked mutations

    Science.gov (United States)

    Williams, Michael; Schwartz, Steven

    2015-03-01

    The previous version of our cardiac thin filament (CTF) model consisted of the troponin complex (cTn), two coiled-coil dimers of tropomyosin (Tm), and 29 actin units. We now present the newest revision of the model to include explicit solvation. The model was developed to continue our study of genetic mutations in the CTF proteins which are linked to familial hypertrophic cardiomyopathies. Binding of calcium to the cTnC subunit causes subtle conformational changes to propagate through the cTnC to the cTnI subunit which then detaches from actin. Conformational changes propagate through to the cTnT subunit, which allows Tm to move into the open position along actin, leading to muscle contraction. Calcium disassociation allows for the reverse to occur, which results in muscle relaxation. The inclusion of explicit TIP3 water solvation allows for the model to get better individual local solvent to protein interactions; which are important when observing the N-lobe calcium binding pocket of the cTnC. We are able to compare in silica and in vitro experimental results to better understand the physiological effects from mutants, such as the R92L/W and F110V/I of the cTnT, on the calcium binding affinity compared to the wild type.

  17. Structure and Dynamics of the Solvation of Bovine Pancreatic Trypsin Inhibitor in Explicit Water: A Comparative Study of the Effects of Solvent and Protein Polarizability

    Science.gov (United States)

    Kim, Byungchan; Young, Tom; Harder, Edward; Friesner, Richard A.; Berne, B. J.

    2009-01-01

    To isolate the effects of the inclusion of polarizability in the force field model on the structure and dynamics of the solvating water in differing electrostatic environments of proteins, we present the results of molecular dynamics simulations of the bovine pancreatic trypsin inhibitor (BPTI) in water with force fields that explicitly include polarization for both the protein and the water. We use three model potentials for water and two model potentials for the protein. Two of the water models and one of the protein models are polarizable. A total of six systems were simulated representing all combinations of these polarizable and nonpolarizable protein and water force fields. We find that all six systems behave in a similar manner in regions of the protein that are weakly electrostatic (either hydrophobic or weakly hydrophilic). However, in the vicinity of regions of the protein with relatively strong electrostatic fields (near positively or negatively charged residues), we observe that the water structure and dynamics are dependent on both the model of the protein and the model of the water. We find that a large part of the dynamical dependence can be described by small changes in the local environments of each region that limit the local density of non-hydrogen-bonded waters, precisely the water molecules that facilitate the dynamical relaxation of the water–water hydrogen bonds. We introduce a simple method for rescaling for this effect. When this is done, we are able to effectively isolate the influence of polarizability on the dynamics. We find that the solvating water’s relaxation is most affected when both the protein and the water models are polarizable. However, when only one model (or neither) is polarizable, the relaxation is similar regardless of the models used. PMID:16853101

  18. Solvation thermodynamics

    CERN Document Server

    Ben-Naim, Arieh

    1987-01-01

    This book deals with a subject that has been studied since the beginning of physical chemistry. Despite the thousands of articles and scores of books devoted to solvation thermodynamics, I feel that some fundamen­ tal and well-established concepts underlying the traditional approach to this subject are not satisfactory and need revision. The main reason for this need is that solvation thermodynamics has traditionally been treated in the context of classical (macroscopic) ther­ modynamics alone. However, solvation is inherently a molecular pro­ cess, dependent upon local rather than macroscopic properties of the system. Therefore, the starting point should be based on statistical mechanical methods. For many years it has been believed that certain thermodynamic quantities, such as the standard free energy (or enthalpy or entropy) of solution, may be used as measures of the corresponding functions of solvation of a given solute in a given solvent. I first challenged this notion in a paper published in 1978 b...

  19. More powerful biomolecular computers

    OpenAIRE

    Blasiak, Janusz; Krasinski, Tadeusz; Poplawski, Tomasz; Sakowski, Sebastian

    2011-01-01

    Biomolecular computers, along with quantum computers, may be a future alternative for traditional, silicon-based computers. Main advantages of biomolecular computers are massive parallel processing of data, expanded capacity of storing information and compatibility with living organisms (first attempts of using biomolecular computers in cancer therapy through blocking of improper genetic information are described in Benenson et al.(2004). However, biomolecular computers have several drawbacks...

  20. Biomolecular Science (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2012-04-01

    A brief fact sheet about NREL Photobiology and Biomolecular Science. The research goal of NREL's Biomolecular Science is to enable cost-competitive advanced lignocellulosic biofuels production by understanding the science critical for overcoming biomass recalcitrance and developing new product and product intermediate pathways. NREL's Photobiology focuses on understanding the capture of solar energy in photosynthetic systems and its use in converting carbon dioxide and water directly into hydrogen and advanced biofuels.

  1. Prediction of Biomolecular Complexes

    KAUST Repository

    Vangone, Anna

    2017-04-12

    Almost all processes in living organisms occur through specific interactions between biomolecules. Any dysfunction of those interactions can lead to pathological events. Understanding such interactions is therefore a crucial step in the investigation of biological systems and a starting point for drug design. In recent years, experimental studies have been devoted to unravel the principles of biomolecular interactions; however, due to experimental difficulties in solving the three-dimensional (3D) structure of biomolecular complexes, the number of available, high-resolution experimental 3D structures does not fulfill the current needs. Therefore, complementary computational approaches to model such interactions are necessary to assist experimentalists since a full understanding of how biomolecules interact (and consequently how they perform their function) only comes from 3D structures which provide crucial atomic details about binding and recognition processes. In this chapter we review approaches to predict biomolecular complexesBiomolecular complexes, introducing the concept of molecular dockingDocking, a technique which uses a combination of geometric, steric and energetics considerations to predict the 3D structure of a biological complex starting from the individual structures of its constituent parts. We provide a mini-guide about docking concepts, its potential and challenges, along with post-docking analysis and a list of related software.

  2. Differential geometry based solvation model II: Lagrangian formulation.

    Science.gov (United States)

    Chen, Zhan; Baker, Nathan A; Wei, G W

    2011-12-01

    Solvation is an elementary process in nature and is of paramount importance to more sophisticated chemical, biological and biomolecular processes. The understanding of solvation is an essential prerequisite for the quantitative description and analysis of biomolecular systems. This work presents a Lagrangian formulation of our differential geometry based solvation models. The Lagrangian representation of biomolecular surfaces has a few utilities/advantages. First, it provides an essential basis for biomolecular visualization, surface electrostatic potential map and visual perception of biomolecules. Additionally, it is consistent with the conventional setting of implicit solvent theories and thus, many existing theoretical algorithms and computational software packages can be directly employed. Finally, the Lagrangian representation does not need to resort to artificially enlarged van der Waals radii as often required by the Eulerian representation in solvation analysis. The main goal of the present work is to analyze the connection, similarity and difference between the Eulerian and Lagrangian formalisms of the solvation model. Such analysis is important to the understanding of the differential geometry based solvation model. The present model extends the scaled particle theory of nonpolar solvation model with a solvent-solute interaction potential. The nonpolar solvation model is completed with a Poisson-Boltzmann (PB) theory based polar solvation model. The differential geometry theory of surfaces is employed to provide a natural description of solvent-solute interfaces. The optimization of the total free energy functional, which encompasses the polar and nonpolar contributions, leads to coupled potential driven geometric flow and PB equations. Due to the development of singularities and nonsmooth manifolds in the Lagrangian representation, the resulting potential-driven geometric flow equation is embedded into the Eulerian representation for the purpose of

  3. Readily Made Solvated Electrons

    Science.gov (United States)

    Ibanez, Jorge G.; Guerra-Millan, Francisco J.; Hugerat, Muhamad; Vazquez-Olavarrieta, Jorge L.; Basheer, Ahmad; Abu-Much, Riam

    2011-01-01

    The existence of solvated electrons has been known for a long time. Key methods for their production (i.e., photoionization of reducing ions, water radiolysis, and the reaction between H[middle dot] and OH[superscript -]) are unsuitable for most school laboratories. We describe a simple experiment to produce liquid ammonia and solvated electrons…

  4. Grid inhomogeneous solvation theory: Hydration structure and thermodynamics of the miniature receptor cucurbit[7]uril

    Science.gov (United States)

    Nguyen, Crystal N.; Kurtzman Young, Tom; Gilson, Michael K.

    2012-01-01

    The displacement of perturbed water upon binding is believed to play a critical role in the thermodynamics of biomolecular recognition, but it is nontrivial to unambiguously define and answer questions about this process. We address this issue by introducing grid inhomogeneous solvation theory (GIST), which discretizes the equations of inhomogeneous solvation theory (IST) onto a three-dimensional grid situated in the region of interest around a solute molecule or complex. Snapshots from explicit solvent simulations are used to estimate localized solvation entropies, energies, and free energies associated with the grid boxes, or voxels, and properly summing these thermodynamic quantities over voxels yields information about hydration thermodynamics. GIST thus provides a smoothly varying representation of water properties as a function of position, rather than focusing on hydration sites where solvent is present at high density. It therefore accounts for full or partial displacement of water from sites that are highly occupied by water, as well as for partly occupied and water-depleted regions around the solute. GIST can also provide a well-defined estimate of the solvation free energy and therefore enables a rigorous end-states analysis of binding. For example, one may not only use a first GIST calculation to project the thermodynamic consequences of displacing water from the surface of a receptor by a ligand, but also account, in a second GIST calculation, for the thermodynamics of subsequent solvent reorganization around the bound complex. In the present study, a first GIST analysis of the molecular host cucurbit[7]uril is found to yield a rich picture of hydration structure and thermodynamics in and around this miniature receptor. One of the most striking results is the observation of a toroidal region of high water density at the center of the host's nonpolar cavity. Despite its high density, the water in this toroidal region is disfavored energetically and

  5. Grid inhomogeneous solvation theory: hydration structure and thermodynamics of the miniature receptor cucurbit[7]uril.

    Science.gov (United States)

    Nguyen, Crystal N; Young, Tom Kurtzman; Gilson, Michael K

    2012-07-28

    The displacement of perturbed water upon binding is believed to play a critical role in the thermodynamics of biomolecular recognition, but it is nontrivial to unambiguously define and answer questions about this process. We address this issue by introducing grid inhomogeneous solvation theory (GIST), which discretizes the equations of inhomogeneous solvation theory (IST) onto a three-dimensional grid situated in the region of interest around a solute molecule or complex. Snapshots from explicit solvent simulations are used to estimate localized solvation entropies, energies, and free energies associated with the grid boxes, or voxels, and properly summing these thermodynamic quantities over voxels yields information about hydration thermodynamics. GIST thus provides a smoothly varying representation of water properties as a function of position, rather than focusing on hydration sites where solvent is present at high density. It therefore accounts for full or partial displacement of water from sites that are highly occupied by water, as well as for partly occupied and water-depleted regions around the solute. GIST can also provide a well-defined estimate of the solvation free energy and therefore enables a rigorous end-states analysis of binding. For example, one may not only use a first GIST calculation to project the thermodynamic consequences of displacing water from the surface of a receptor by a ligand, but also account, in a second GIST calculation, for the thermodynamics of subsequent solvent reorganization around the bound complex. In the present study, a first GIST analysis of the molecular host cucurbit[7]uril is found to yield a rich picture of hydration structure and thermodynamics in and around this miniature receptor. One of the most striking results is the observation of a toroidal region of high water density at the center of the host's nonpolar cavity. Despite its high density, the water in this toroidal region is disfavored energetically and

  6. Programming in biomolecular computation

    DEFF Research Database (Denmark)

    Hartmann, Lars Røeboe; Jones, Neil; Simonsen, Jakob Grue

    2011-01-01

    Our goal is to provide a top-down approach to biomolecular computation. In spite of widespread discussion about connections between biology and computation, one question seems notable by its absence: Where are the programs? We identify a number of common features in programming that seem...... conspicuously absent from the literature on biomolecular computing; to partially redress this absence, we introduce a model of computation that is evidently programmable, by programs reminiscent of low-level computer machine code; and at the same time biologically plausible: its functioning is defined...... by a single and relatively small set of chemical-like reaction rules. Further properties: the model is stored-program: programs are the same as data, so programs are not only executable, but are also compilable and interpretable. It is universal: all computable functions can be computed (in natural ways...

  7. Biomolecular Sciences: uniting Biology and Chemistry

    NARCIS (Netherlands)

    Vrieling, Engel

    2017-01-01

    Biomolecular Sciences: uniting Biology and Chemistry www.rug.nl/research/gbb The scientific discoveries in biomolecular sciences have benefitted enormously from technological innovations. At the Groningen Biomolecular Science and Biotechnology Institute (GBB) we now sequence a genome in days,

  8. Biomolecular EPR spectroscopy

    CERN Document Server

    Hagen, Wilfred Raymond

    2008-01-01

    Comprehensive, Up-to-Date Coverage of Spectroscopy Theory and its Applications to Biological SystemsAlthough a multitude of books have been published about spectroscopy, most of them only occasionally refer to biological systems and the specific problems of biomolecular EPR (bioEPR). Biomolecular EPR Spectroscopy provides a practical introduction to bioEPR and demonstrates how this remarkable tool allows researchers to delve into the structural, functional, and analytical analysis of paramagnetic molecules found in the biochemistry of all species on the planet. A Must-Have Reference in an Intrinsically Multidisciplinary FieldThis authoritative reference seamlessly covers all important bioEPR applications, including low-spin and high-spin metalloproteins, spin traps and spin lables, interaction between active sites, and redox systems. It is loaded with practical tricks as well as do's and don'ts that are based on the author's 30 years of experience in the field. The book also comes with an unprecedented set of...

  9. Exploring biomolecular energy landscapes.

    Science.gov (United States)

    Joseph, Jerelle A; Röder, Konstantin; Chakraborty, Debayan; Mantell, Rosemary G; Wales, David J

    2017-06-27

    The potential energy landscape perspective provides both a conceptual and a computational framework for predicting, understanding and designing molecular properties. In this Feature Article, we highlight some recent advances that greatly facilitate structure prediction and analysis of global thermodynamics and kinetics in proteins and nucleic acids. The geometry optimisation procedures, on which these calculations are based, can be accelerated significantly using local rigidification of selected degrees of freedom, and through implementations on graphics processing units. Results of progressive local rigidification are first summarised for trpzip1, including a systematic analysis of the heat capacity and rearrangement rates. Benchmarks for all the essential optimisation procedures are then provided for a variety of proteins. Applications are then illustrated from a study of how mutation affects the energy landscape for a coiled-coil protein, and for transitions in helix morphology for a DNA duplex. Both systems exhibit an intrinsically multifunnel landscape, with the potential to act as biomolecular switches.

  10. Programming in biomolecular computation

    DEFF Research Database (Denmark)

    Hartmann, Lars Røeboe; Jones, Neil; Simonsen, Jakob Grue

    2010-01-01

    Our goal is to provide a top-down approach to biomolecular computation. In spite of widespread discussion about connections between biology and computation, one question seems notable by its absence: Where are the programs? We introduce a model of computation that is evidently programmable......, by programs reminiscent of low-level computer machine code; and at the same time biologically plausible: its functioning is defined by a single and relatively small set of chemical-like reaction rules. Further properties: the model is stored-program: programs are the same as data, so programs are not only...... in a strong sense: a universal algorithm exists, that is able to execute any program, and is not asymptotically inefficient. A prototype model has been implemented (for now in silico on a conventional computer). This work opens new perspectives on just how computation may be specified at the biological level....

  11. Adaptive resolution simulations of biomolecular systems.

    Science.gov (United States)

    Zavadlav, Julija; Bevc, Staš; Praprotnik, Matej

    2017-12-01

    In this review article, we discuss and analyze some recently developed hybrid atomistic-mesoscopic solvent models for multiscale biomolecular simulations. We focus on the biomolecular applications of the adaptive resolution scheme (AdResS), which allows solvent molecules to change their resolution back and forth between atomistic and coarse-grained representations according to their positions in the system. First, we discuss coupling of atomistic and coarse-grained models of salt solution using a 1-to-1 molecular mapping-i.e., one coarse-grained bead represents one water molecule-for development of a multiscale salt solution model. In order to make use of coarse-grained molecular models that are compatible with the MARTINI force field, one has to resort to a supramolecular mapping, in particular to a 4-to-1 mapping, where four water molecules are represented with one coarse-grained bead. To this end, bundled atomistic water models are employed, i.e., the relative movement of water molecules that are mapped to the same coarse-grained bead is restricted by employing harmonic springs. Supramolecular coupling has recently also been extended to polarizable coarse-grained water models with explicit charges. Since these coarse-grained models consist of several interaction sites, orientational degrees of freedom of the atomistic and coarse-grained representations are coupled via a harmonic energy penalty term. The latter aligns the dipole moments of both representations. The reviewed multiscale solvent models are ready to be used in biomolecular simulations, as illustrated in a few examples.

  12. Explicit Interaction

    DEFF Research Database (Denmark)

    Löwgren, Jonas; Eriksen, Mette Agger; Linde, Per

    2006-01-01

    as an interpretation of palpability, comprising usability as well as patient empowerment and socially performative issues. We present a prototype environment for video recording during physiotherapeutical consultation which illustrates our current thoughts on explicit interaction and serves as material for further...

  13. Recent progress in biomolecular engineering.

    Science.gov (United States)

    Ryu, D D; Nam, D H

    2000-01-01

    During the next decade or so, there will be significant and impressive advances in biomolecular engineering, especially in our understanding of the biological roles of various biomolecules inside the cell. The advances in high throughput screening technology for discovery of target molecules and the accumulation of functional genomics and proteomics data at accelerating rates will enable us to design and discover novel biomolecules and proteins on a rational basis in diverse areas of pharmaceutical, agricultural, industrial, and environmental applications. As an applied molecular evolution technology, DNA shuffling will play a key role in biomolecular engineering. In contrast to the point mutation techniques, DNA shuffling exchanges large functional domains of sequences to search for the best candidate molecule, thus mimicking and accelerating the process of sexual recombination in the evolution of life. The phage-display system of combinatorial peptide libraries will be extensively exploited to design and create many novel proteins, as a result of the relative ease of screening and identifying desirable proteins. Even though this system has so far been employed mainly in screening the combinatorial antibody libraries, its application will be extended further into the science of protein-receptor or protein-ligand interactions. The bioinformatics for genome and proteome analyses will contribute substantially toward ever more accelerated advances in the pharmaceutical industry. Biomolecular engineering will no doubt become one of the most important scientific disciplines, because it will enable systematic and comprehensive analyses of gene expression patterns in both normal and diseased cells, as well as the discovery of many new high-value molecules. When the functional genomics database, EST and SAGE techniques, microarray technique, and proteome analysis by 2-dimensional gel electrophoresis or capillary electrophoresis in combination with mass spectrometer are all

  14. Determination of solvation kinetics in supercritical fluids

    Energy Technology Data Exchange (ETDEWEB)

    Bright, F.V.

    1993-01-01

    Objective was to study solvation processes in pure and entrainer-modified supercritical fluids. Specific topics were: Kinetics for solvation in supercritical media, influence on entrainers on solvation, reversibility of solvation, effects of solvation on intramolecular solute-solute interaction kinetics, and impact of fluid density on these processes. Time-resolved fluorescence spectroscopy was used as the main analytical tool. A summary is given of the 2.5 years' research.

  15. Energy-based analysis of biomolecular pathways.

    Science.gov (United States)

    Gawthrop, Peter J; Crampin, Edmund J

    2017-06-01

    Decomposition of biomolecular reaction networks into pathways is a powerful approach to the analysis of metabolic and signalling networks. Current approaches based on analysis of the stoichiometric matrix reveal information about steady-state mass flows (reaction rates) through the network. In this work, we show how pathway analysis of biomolecular networks can be extended using an energy-based approach to provide information about energy flows through the network. This energy-based approach is developed using the engineering-inspired bond graph methodology to represent biomolecular reaction networks. The approach is introduced using glycolysis as an exemplar; and is then applied to analyse the efficiency of free energy transduction in a biomolecular cycle model of a transporter protein [sodium-glucose transport protein 1 (SGLT1)]. The overall aim of our work is to present a framework for modelling and analysis of biomolecular reactions and processes which considers energy flows and losses as well as mass transport.

  16. CHARMM-GUI 10 years for biomolecular modeling and simulation.

    Science.gov (United States)

    Jo, Sunhwan; Cheng, Xi; Lee, Jumin; Kim, Seonghoon; Park, Sang-Jun; Patel, Dhilon S; Beaven, Andrew H; Lee, Kyu Il; Rui, Huan; Park, Soohyung; Lee, Hui Sun; Roux, Benoît; MacKerell, Alexander D; Klauda, Jeffrey B; Qi, Yifei; Im, Wonpil

    2017-06-05

    CHARMM-GUI, http://www.charmm-gui.org, is a web-based graphical user interface that prepares complex biomolecular systems for molecular simulations. CHARMM-GUI creates input files for a number of programs including CHARMM, NAMD, GROMACS, AMBER, GENESIS, LAMMPS, Desmond, OpenMM, and CHARMM/OpenMM. Since its original development in 2006, CHARMM-GUI has been widely adopted for various purposes and now contains a number of different modules designed to set up a broad range of simulations: (1) PDB Reader & Manipulator, Glycan Reader, and Ligand Reader & Modeler for reading and modifying molecules; (2) Quick MD Simulator, Membrane Builder, Nanodisc Builder, HMMM Builder, Monolayer Builder, Micelle Builder, and Hex Phase Builder for building all-atom simulation systems in various environments; (3) PACE CG Builder and Martini Maker for building coarse-grained simulation systems; (4) DEER Facilitator and MDFF/xMDFF Utilizer for experimentally guided simulations; (5) Implicit Solvent Modeler, PBEQ-Solver, and GCMC/BD Ion Simulator for implicit solvent related calculations; (6) Ligand Binder for ligand solvation and binding free energy simulations; and (7) Drude Prepper for preparation of simulations with the CHARMM Drude polarizable force field. Recently, new modules have been integrated into CHARMM-GUI, such as Glycolipid Modeler for generation of various glycolipid structures, and LPS Modeler for generation of lipopolysaccharide structures from various Gram-negative bacteria. These new features together with existing modules are expected to facilitate advanced molecular modeling and simulation thereby leading to an improved understanding of the structure and dynamics of complex biomolecular systems. Here, we briefly review these capabilities and discuss potential future directions in the CHARMM-GUI development project. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Biomolecular NMR: Past and future.

    Science.gov (United States)

    Markley, John L; Westler, William Milo

    2017-08-15

    The editors of this special volume suggested this topic, presumably because of the perspective lent by our combined >90-year association with biomolecular NMR. What follows is our personal experience with the evolution of the field, which we hope will illustrate the trajectory of change over the years. As for the future, one can confidently predict that it will involve unexpected advances. Our narrative is colored by our experience in using the NMR Facility for Biomedical Studies at Carnegie-Mellon University (Pittsburgh) and in developing similar facilities at Purdue (1977-1984) and the University of Wisconsin-Madison (1984-). We have enjoyed developing NMR technology and making it available to collaborators and users of these facilities. Our group's association with the Biological Magnetic Resonance data Bank (BMRB) and with the Worldwide Protein Data Bank (wwPDB) has also been rewarding. Of course, many groups contributed to the early growth and development of biomolecular NMR, and our brief personal account certainly omits many important milestones. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Communication: Counter-ion solvation and anomalous low-angle scattering in salt-free polyelectrolyte solutions

    Science.gov (United States)

    Chremos, Alexandros; Douglas, Jack F.

    2017-12-01

    We investigate the influence of counter-ion solvation on the homogeneity of salt-free polyelectrolyte solutions based on a coarse-grained model that includes an explicit solvent. We show that the solvation of the counter-ions can cause a transformation between a nearly homogeneous to a non-uniform polymer solution, in which there is both a chain clustering and the formation of large charge-free domains, i.e., "voids." The emergence of these heterogeneous structures induced by counter-ion solvation is accompanied by the localization and formation of counter-ion rich domains that are symptomatic of emergent effective long-range attractive interchain interactions.

  19. Communication: Counter-ion solvation and anomalous low-angle scattering in salt-free polyelectrolyte solutions.

    Science.gov (United States)

    Chremos, Alexandros; Douglas, Jack F

    2017-12-28

    We investigate the influence of counter-ion solvation on the homogeneity of salt-free polyelectrolyte solutions based on a coarse-grained model that includes an explicit solvent. We show that the solvation of the counter-ions can cause a transformation between a nearly homogeneous to a non-uniform polymer solution, in which there is both a chain clustering and the formation of large charge-free domains, i.e., "voids." The emergence of these heterogeneous structures induced by counter-ion solvation is accompanied by the localization and formation of counter-ion rich domains that are symptomatic of emergent effective long-range attractive interchain interactions.

  20. Biomolecular

    Directory of Open Access Journals (Sweden)

    K. Sampath

    2017-05-01

    Full Text Available In our search for new anticancer and DNA interacting agents, ruthenium(III thiosemicarbazone complexes of the type [RuCl2(EPh3L] (where E = P/As; L = monobasic tridentate thiosemicarbazone ligand were synthesized and characterized by physico-chemical and spectroscopic methods. All the ligands and complexes exhibit noticeable growth inhibition against fungal species and bacterial species. The interactions of these complexes with biomolecule, CT-DNA were investigated by absorbance measurement and gel electrophoresis. Absorption spectral study indicates that the ruthenium(III complexes have an intrinsic binding constant in the range of 1.0–3.6 × 104 M−1. The complexes exhibit a remarkable DNA cleavage activity with CT-DNA in the presence of hydroxyl radical. The cleavage activity was carried out with the variation of the concentration of complexes and incubation time. Further, an in vitro cytotoxicity study of the complexes exhibited antitumor activity against the HeLa tumor cell line. This research may provide valuable insight into the interactions of metal complexes with DNA and cytotoxicity, knowledge that is an excellent back drop for the rational design of promising drugs.

  1. Force Field Model of Periodic Trends in Biomolecular Halogen Bonds.

    Science.gov (United States)

    Scholfield, Matthew R; Ford, Melissa Coates; Vander Zanden, Crystal M; Billman, M Marie; Ho, P Shing; Rappé, Anthony K

    2015-07-23

    The study of the noncovalent interaction now defined as a halogen bond (X-bond) has become one of the fastest growing areas in experimental and theoretical chemistry--its applications as a design tool are highly extensive. The significance of the interaction in biology has only recently been recognized, but has now become important in medicinal chemistry. We had previously derived a set of empirical potential energy functions to model the structure-energy relationships for bromines in biomolecular X-bonds (BXBs). Here, we have extended this force field for BXBs (ffBXB) to the halogens (Cl, Br, and I) that are commonly seen to form stable X-bonds. The ffBXB calculated energies show a remarkable one-to-one linear relationship to explicit BXB energies determined from an experimental DNA junction system, thereby validating the approach and the model. The resulting parameters allow us to interpret the stabilizing effects of BXBs in terms of well-defined physical properties of the halogen atoms, including their size, shape, and charge, showing periodic trends that are predictable along the Group VII column of elements. Consequently, we have established the ffBXB as an accurate computational tool that can be applied, for example, for the design of new therapeutic compounds against clinically important targets and new biomolecular-based materials.

  2. Isotachophoresis applied to biomolecular reactions.

    Science.gov (United States)

    Eid, C; Santiago, J G

    2017-12-19

    This review discusses research developments and applications of isotachophoresis (ITP) to the initiation, control, and acceleration of chemical reactions, emphasizing reactions involving biomolecular reactants such as nucleic acids, proteins, and live cells. ITP is a versatile technique which requires no specific geometric design or material, and is compatible with a wide range of microfluidic and automated platforms. Though ITP has traditionally been used as a purification and separation technique, recent years have seen its emergence as a method to automate and speed up chemical reactions. ITP has been used to demonstrate up to 14 000-fold acceleration of nucleic acid assays, and has been used to enhance lateral flow and other immunoassays, and even whole bacterial cell detection assays. We here classify these studies into two categories: homogeneous (all reactants in solution) and heterogeneous (at least one reactant immobilized on a solid surface) assay configurations. For each category, we review and describe physical modeling and scaling of ITP-aided reaction assays, and elucidate key principles in ITP assay design. We summarize experimental advances, and identify common threads and approaches which researchers have used to optimize assay performance. Lastly, we propose unaddressed challenges and opportunities that could further improve these applications of ITP.

  3. A Structural Investigation of the D O Solvated, Acetone Solvated and ...

    African Journals Online (AJOL)

    NICO

    DABCO = 1,4-diazabicyclo[2.2.2]octane); 1 (D2O solvate) and2(acetone solvate), and the mononuclear salt [(η5-C5H5)(CO)2Fe(DABCO)]BF4,3, have been synthesized and structur- ally characterized. The D2O solvate, 1 forms crystals in the ...

  4. Thiolated gold nanoparticle solvation in near-critical fluids: The role of density, temperature, and topology

    Science.gov (United States)

    Yadav, Hari O. S.; Chakravarty, Charusita

    2017-05-01

    We employ molecular dynamics simulations to study the structure and solvation thermodynamics of thiolated gold nanoparticles of size 1.2 and 1.6 nm with ligand of chain length 8-16 carbons in ethane and propane over a wide range of densities close to the critical isotherm. The Helmholtz free energy is estimated by explicitly calculating the change in entropy and internal energy of solvation, and the effect of density and temperature on fluctuation-driven inherent anisotropy in the ligand corona is characterized. Since the topological variation further accentuates this instantaneous asymmetry in the ligand cloud, the anisotropy with varying surface coverage and chain length is also studied including the solvent contributions to the entropic and energetic metrics. Our results are consistent with the experiment, suggesting a route of obtaining structural insights into solvation thermodynamics that could be useful for understanding the stability of nanoparticle dispersions.

  5. MTS-MD of Biomolecules Steered with 3D-RISM-KH Mean Solvation Forces Accelerated with Generalized Solvation Force Extrapolation.

    Science.gov (United States)

    Omelyan, Igor; Kovalenko, Andriy

    2015-04-14

    with explicit solvent. We have been able to fold the miniprotein from a fully denatured, extended state in about 60 ns of quasidynamics steered with 3D-RISM-KH mean solvation forces, compared to the average physical folding time of 4-9 μs observed in experiment.

  6. Variational Implicit Solvation with Solute Molecular Mechanics: From Diffuse-Interface to Sharp-Interface Models.

    Science.gov (United States)

    Li, Bo; Zhao, Yanxiang

    2013-01-01

    Central in a variational implicit-solvent description of biomolecular solvation is an effective free-energy functional of the solute atomic positions and the solute-solvent interface (i.e., the dielectric boundary). The free-energy functional couples together the solute molecular mechanical interaction energy, the solute-solvent interfacial energy, the solute-solvent van der Waals interaction energy, and the electrostatic energy. In recent years, the sharp-interface version of the variational implicit-solvent model has been developed and used for numerical computations of molecular solvation. In this work, we propose a diffuse-interface version of the variational implicit-solvent model with solute molecular mechanics. We also analyze both the sharp-interface and diffuse-interface models. We prove the existence of free-energy minimizers and obtain their bounds. We also prove the convergence of the diffuse-interface model to the sharp-interface model in the sense of Γ-convergence. We further discuss properties of sharp-interface free-energy minimizers, the boundary conditions and the coupling of the Poisson-Boltzmann equation in the diffuse-interface model, and the convergence of forces from diffuse-interface to sharp-interface descriptions. Our analysis relies on the previous works on the problem of minimizing surface areas and on our observations on the coupling between solute molecular mechanical interactions with the continuum solvent. Our studies justify rigorously the self consistency of the proposed diffuse-interface variational models of implicit solvation.

  7. Explicit proton transfer in classical molecular dynamics simulations

    OpenAIRE

    Wolf, Maarten G.; Groenhof, Gerrit

    2014-01-01

    We present Hydrogen Dynamics (HYDYN), a method that allows explicit proton transfer in classical force field molecular dynamics simulations at thermodynamic equilibrium. HYDYN reproduces the characteristic properties of the excess proton in water, from the special pair dance, to the continuous fluctuation between the limiting Eigen and Zundel complexes, and the water reorientation beyond the first solvation layer. Advantages of HYDYN with respect to existing methods are computational efficien...

  8. Explicit-ion Effects in the Coil-Globule Transition of Weak Polyelectrolytes

    Science.gov (United States)

    Sikora, Benjamin J.; Whitmer, Jonathan K.

    The first-order coil-globule transition in weak (annealed) polyelectrolytes involves a subtle balance of pH, charge strength, and solvation forces. In this work, we utilize a coarse-grain hybrid grand-canonical Monte Carlo and Molecular Dynamics approach to explore the free energetic topography of a model hydrophobic polybase [representing poly(2-vinylpyridine) (P2VP)] and explore the role of salt concentration/valency in influencing polyelectrolyte conformations using both an implicit Debye-Hückel and explicit salt approach. Our simulations reproduce the experimentally measured behavior for dilute annealed polyelectrolytes, and present a solid foundation for understanding pH responsive polyelectrolyte materials.

  9. Calculation of relative free energies for ligand-protein binding, solvation, and conformational transitions using the GROMOS software.

    Science.gov (United States)

    Riniker, Sereina; Christ, Clara D; Hansen, Halvor S; Hünenberger, Philippe H; Oostenbrink, Chris; Steiner, Denise; van Gunsteren, Wilfred F

    2011-11-24

    The calculation of the relative free energies of ligand-protein binding, of solvation for different compounds, and of different conformational states of a polypeptide is of considerable interest in the design or selection of potential enzyme inhibitors. Since such processes in aqueous solution generally comprise energetic and entropic contributions from many molecular configurations, adequate sampling of the relevant parts of configurational space is required and can be achieved through molecular dynamics simulations. Various techniques to obtain converged ensemble averages and their implementation in the GROMOS software for biomolecular simulation are discussed, and examples of their application to biomolecules in aqueous solution are given. © 2011 American Chemical Society

  10. Solvated Electrons in Organic Chemistry Laboratory

    Science.gov (United States)

    Ilich, Predrag-Peter; McCormick, Kathleen R.; Atkins, Adam D.; Mell, Geoffrey J.; Flaherty, Timothy J.; Bruck, Martin J.; Goodrich, Heather A.; Hefel, Aaron L.; Juranic, Nenad; Seleem, Suzanne

    2010-01-01

    A novel experiment is described in which solvated electrons in liquid ammonia reduce a benzyl alcohol carbon without affecting the aromatic ring. The reductive activity of solvated electrons can be partially or completely quenched through the addition of electron scavengers to the reaction mixture. The effectiveness of these scavengers was found…

  11. Updated Abraham solvation parameters for polychlorinated biphenyls

    NARCIS (Netherlands)

    Noort, van P.C.M.; Haftka, J.J.H.; Parsons, J.R.

    2010-01-01

    This study shows that the recently published polychlorinated biphenyl (PCB) Abraham solvation parameters predict PCB air-n-hexadecane and n-octanol-water partition coefficients very poorly, especially for highly ortho-chlorinated congeners. Therefore, an updated set of PCB solvation parameters was

  12. Updated Abraham solvation parameters for polychlorinated biphenyls

    NARCIS (Netherlands)

    van Noort, P.C.M.; Haftka, J.J.H.; Parsons, J.R.

    2010-01-01

    This study shows that the recently published polychlorinated biphenyl (PCB) Abraham solvation parameters predict PCB air−n-hexadecane and n-octanol−water partition coefficients very poorly, especially for highly ortho-chlorinated congeners. Therefore, an updated set of PCB solvation parameters was

  13. Biomolecular crystals for material applications and a mechanistic study of an iron oxide nanoparticle synthesis

    Science.gov (United States)

    Falkner, Joshua Charles

    The three projects within this work address the difficulties of controlling biomolecular crystal formats (i.e. size and shape), producing 3-D ordered composite materials from biomolecular crystal templates, and understanding the mechanism of a practical iron oxide synthesis. The unifying thread consistent throughout these three topics is the development of methods to manipulate nanomaterials using a bottom-up approach. Biomolecular crystals are nanometer to millimeter sized crystals that have well ordered mesoporous solvent channels. The overall physical dimensions of these crystals are highly dependent on crystallization conditions. The controlled growth of micro- and nanoprotein crystals was studied to provide new pathways for creating smaller crystalline protein materials. This method produced tetragonal hen egg-white lysozyme crystals (250--100,000 nm) with near monodisperse size distributions (membranes or templates. In this work, the porous structure of larger cowpea mosaic virus crystals was used to template metal nanoparticle growth within the body centered cubic crystalline network. The final composite material was found to have long range ordering of palladium and platinum nonocrystal aggregates (10nm) with symmetry consistent to the virus template. Nanoparticle synthesis itself is an immense field of study with an array of diverse applications. The final piece of this work investigates the mechanism behind a previously developed iron oxide synthesis to gain more understanding and direction to future synthesis strategies. The particle growth mechanism was found to proceed by the formation of a solvated iron(III)oleate complex followed by a reduction of iron (III) to iron (II). This unstable iron(II) nucleates to form a wustite (FeO) core which serves as an epitaxial surface for the magnetite (Fe3O4) shell growth. This method produces spherical particles (6-60nm) with relative size distributions of less than 15%.

  14. Biomolecular computers with multiple restriction enzymes

    Directory of Open Access Journals (Sweden)

    Sebastian Sakowski

    2017-10-01

    Full Text Available Abstract The development of conventional, silicon-based computers has several limitations, including some related to the Heisenberg uncertainty principle and the von Neumann “bottleneck”. Biomolecular computers based on DNA and proteins are largely free of these disadvantages and, along with quantum computers, are reasonable alternatives to their conventional counterparts in some applications. The idea of a DNA computer proposed by Ehud Shapiro’s group at the Weizmann Institute of Science was developed using one restriction enzyme as hardware and DNA fragments (the transition molecules as software and input/output signals. This computer represented a two-state two-symbol finite automaton that was subsequently extended by using two restriction enzymes. In this paper, we propose the idea of a multistate biomolecular computer with multiple commercially available restriction enzymes as hardware. Additionally, an algorithmic method for the construction of transition molecules in the DNA computer based on the use of multiple restriction enzymes is presented. We use this method to construct multistate, biomolecular, nondeterministic finite automata with four commercially available restriction enzymes as hardware. We also describe an experimental applicaton of this theoretical model to a biomolecular finite automaton made of four endonucleases.

  15. Biomolecular computers with multiple restriction enzymes.

    Science.gov (United States)

    Sakowski, Sebastian; Krasinski, Tadeusz; Waldmajer, Jacek; Sarnik, Joanna; Blasiak, Janusz; Poplawski, Tomasz

    2017-01-01

    The development of conventional, silicon-based computers has several limitations, including some related to the Heisenberg uncertainty principle and the von Neumann "bottleneck". Biomolecular computers based on DNA and proteins are largely free of these disadvantages and, along with quantum computers, are reasonable alternatives to their conventional counterparts in some applications. The idea of a DNA computer proposed by Ehud Shapiro's group at the Weizmann Institute of Science was developed using one restriction enzyme as hardware and DNA fragments (the transition molecules) as software and input/output signals. This computer represented a two-state two-symbol finite automaton that was subsequently extended by using two restriction enzymes. In this paper, we propose the idea of a multistate biomolecular computer with multiple commercially available restriction enzymes as hardware. Additionally, an algorithmic method for the construction of transition molecules in the DNA computer based on the use of multiple restriction enzymes is presented. We use this method to construct multistate, biomolecular, nondeterministic finite automata with four commercially available restriction enzymes as hardware. We also describe an experimental applicaton of this theoretical model to a biomolecular finite automaton made of four endonucleases.

  16. Biomolecular engineering for nanobio/bionanotechnology.

    Science.gov (United States)

    Nagamune, Teruyuki

    2017-01-01

    Biomolecular engineering can be used to purposefully manipulate biomolecules, such as peptides, proteins, nucleic acids and lipids, within the framework of the relations among their structures, functions and properties, as well as their applicability to such areas as developing novel biomaterials, biosensing, bioimaging, and clinical diagnostics and therapeutics. Nanotechnology can also be used to design and tune the sizes, shapes, properties and functionality of nanomaterials. As such, there are considerable overlaps between nanotechnology and biomolecular engineering, in that both are concerned with the structure and behavior of materials on the nanometer scale or smaller. Therefore, in combination with nanotechnology, biomolecular engineering is expected to open up new fields of nanobio/bionanotechnology and to contribute to the development of novel nanobiomaterials, nanobiodevices and nanobiosystems. This review highlights recent studies using engineered biological molecules (e.g., oligonucleotides, peptides, proteins, enzymes, polysaccharides, lipids, biological cofactors and ligands) combined with functional nanomaterials in nanobio/bionanotechnology applications, including therapeutics, diagnostics, biosensing, bioanalysis and biocatalysts. Furthermore, this review focuses on five areas of recent advances in biomolecular engineering: (a) nucleic acid engineering, (b) gene engineering, (c) protein engineering, (d) chemical and enzymatic conjugation technologies, and (e) linker engineering. Precisely engineered nanobiomaterials, nanobiodevices and nanobiosystems are anticipated to emerge as next-generation platforms for bioelectronics, biosensors, biocatalysts, molecular imaging modalities, biological actuators, and biomedical applications.

  17. Origin of organic molecules and biomolecular homochirality.

    Science.gov (United States)

    Podlech, J

    2001-01-01

    Theories about the origin of biomolecular homochirality, which seems to be a prerequisite for the creation of life, are discussed. First, possible terrestrial and extraterrestrial sources of organic molecules are outlined. Then, mechanisms for the formation of enantiomerically enriched compounds and for the amplification of their chirality are described.

  18. Conducting polymer based biomolecular electronic devices

    Indian Academy of Sciences (India)

    Our group has been actively working towards the application of conducting polymers to Schottky diodes, metal–insulator–semiconductor (MIS) devices and biosensors for the past 10 years. This paper is a review of some of the results obtained at our laboratory in the area of conducting polymer biomolecular electronics.

  19. Conducting polymer based biomolecular electronic devices

    Indian Academy of Sciences (India)

    Our group has been actively working towards the application of conducting polymers to Schottky diodes, metal– insulator–semiconductor (MIS) devices and biosensors for the past 10 years. This paper is a review of some of the results obtained at our laboratory in the area of conducting polymer biomolecular electronics.

  20. Biomolecular engineering for nanobio/bionanotechnology

    Science.gov (United States)

    Nagamune, Teruyuki

    2017-04-01

    Biomolecular engineering can be used to purposefully manipulate biomolecules, such as peptides, proteins, nucleic acids and lipids, within the framework of the relations among their structures, functions and properties, as well as their applicability to such areas as developing novel biomaterials, biosensing, bioimaging, and clinical diagnostics and therapeutics. Nanotechnology can also be used to design and tune the sizes, shapes, properties and functionality of nanomaterials. As such, there are considerable overlaps between nanotechnology and biomolecular engineering, in that both are concerned with the structure and behavior of materials on the nanometer scale or smaller. Therefore, in combination with nanotechnology, biomolecular engineering is expected to open up new fields of nanobio/bionanotechnology and to contribute to the development of novel nanobiomaterials, nanobiodevices and nanobiosystems. This review highlights recent studies using engineered biological molecules (e.g., oligonucleotides, peptides, proteins, enzymes, polysaccharides, lipids, biological cofactors and ligands) combined with functional nanomaterials in nanobio/bionanotechnology applications, including therapeutics, diagnostics, biosensing, bioanalysis and biocatalysts. Furthermore, this review focuses on five areas of recent advances in biomolecular engineering: (a) nucleic acid engineering, (b) gene engineering, (c) protein engineering, (d) chemical and enzymatic conjugation technologies, and (e) linker engineering. Precisely engineered nanobiomaterials, nanobiodevices and nanobiosystems are anticipated to emerge as next-generation platforms for bioelectronics, biosensors, biocatalysts, molecular imaging modalities, biological actuators, and biomedical applications.

  1. Solvation of fullerene and fulleride ion in liquid ammonia: structure and dynamics of the solvation shells.

    Science.gov (United States)

    Rana, Malay Kumar; Chandra, Amalendu

    2012-10-07

    Molecular dynamics simulations have been performed to investigate the solvation characteristics of neutral fullerene (C(60)) and charged fulleride anion (C(60)(5-)) in liquid ammonia. Potassium ions are present as counterions in the system containing fulleride ion. In addition to solvation characteristics, dynamical properties of solvation shells are also found out for both the neutral and anionic solutes. Our results reveal the presence of a rather large solvation shell of ammonia molecules around the C(60)(5-) ion. It is found that the ammonia molecules are more closely packed in the first solvation shell of C(60)(5-) than that of C(60). The distributions of ammonia molecules in the solvation shells of C(60) and C(60)(5-) solutes together with hydrogen bonding characteristics of the solvent in different solvation shells are investigated. It is found that the solvation of the small counterions (K(+)) in liquid ammonia is affected very little by the presence of the large C(60)(5-) anion. Regarding the dynamics of ammonia in solvation shells, it is found that the residence, translational and rotational dynamics of ammonia molecules differ significantly between the solvation shells of the neutral and charged fullerene solutes, especially in the first solvation shells. The average lifetimes of ammonia-ammonia hydrogen bonds are calculated from both continuous and intermittent hydrogen bond correlation functions. The calculations of binding energies reveal that the hydrogen bonds are weaker, hence short lived in the solvation shell of C(60)(5-) compared to those in the solvation shell of neutral C(60) and also in bulk liquid ammonia.

  2. Converting biomolecular modelling data based on an XML representation.

    Science.gov (United States)

    Sun, Yudong; McKeever, Steve

    2008-08-25

    Biomolecular modelling has provided computational simulation based methods for investigating biological processes from quantum chemical to cellular levels. Modelling such microscopic processes requires atomic description of a biological system and conducts in fine timesteps. Consequently the simulations are extremely computationally demanding. To tackle this limitation, different biomolecular models have to be integrated in order to achieve high-performance simulations. The integration of diverse biomolecular models needs to convert molecular data between different data representations of different models. This data conversion is often non-trivial, requires extensive human input and is inevitably error prone. In this paper we present an automated data conversion method for biomolecular simulations between molecular dynamics and quantum mechanics/molecular mechanics models. Our approach is developed around an XML data representation called BioSimML (Biomolecular Simulation Markup Language). BioSimML provides a domain specific data representation for biomolecular modelling which can effciently support data interoperability between different biomolecular simulation models and data formats.

  3. Energy dissipation in biomolecular machines

    Energy Technology Data Exchange (ETDEWEB)

    Lervik, Anders

    2012-07-01

    The operation of a molecular pump, the calcium pump of sarcoplasmic reticulum is studied using mesoscopic non-equilibrium thermodynamics and molecular dynamics. The mesoscopic non-equilibrium thermodynamic description of the pump is compared to the description obtained in the framework of Hill for kinetic enzyme cycles. By comparing these two descriptions at isothermal conditions, they are found to be equivalent. This supports the validity of the mesoscopic approach. An extension of the mesoscopic non-equilibrium framework to also include a heat flux and the corresponding temperature difference is proposed. This can be used to model phenomena such as non-shivering thermogenesis, a process which lack a theoretical description in the kinetic cycle picture. Further, the heat transfer in the calcium pump is studied using molecular dynamics. This is done in order to obtain phenomenological parameters that can be used for the modeling of thermogenesis. A non-stationary non-equilibrium molecular dynamics approach is developed, which may be used to study heat transfer between a small object and the surrounding solvent. This methodology is applied to the calcium pump solvated in water. It is found that the thermal conductivity of the protein is low (0.2 W K-1 m-1) compared to water (0.6 WK-1 m-1). This means that the protein may sustain a large temperature gradient across its structure. The simulations also show that the protein-water surface is important for the heat transfer. The time scale for vibrational energy relaxation is found to be of order 10/100 ps which strengthens the local equilibrium assumption of mesoscopic non-equilibrium thermodynamics. Mesoscopic non-equilibrium thermodynamics is also applied to calculate the thermodynamic efficiency of the calcium pump embedded in lipid bilayers of varying length and from different tissues. This is done in order to show the applicability of mesoscopic non-equilibrium thermodynamics to interpret experimental data. The

  4. Determination of solvation kinetics in supercritical fluids. Summary report

    Energy Technology Data Exchange (ETDEWEB)

    Bright, F.V.

    1993-01-01

    Objective was to study solvation processes in pure and entrainer-modified supercritical fluids. Specific topics were: Kinetics for solvation in supercritical media, influence on entrainers on solvation, reversibility of solvation, effects of solvation on intramolecular solute-solute interaction kinetics, and impact of fluid density on these processes. Time-resolved fluorescence spectroscopy was used as the main analytical tool. A summary is given of the 2.5 years` research.

  5. Molecular modeling of nucleic Acid structure: electrostatics and solvation.

    Science.gov (United States)

    Bergonzo, Christina; Galindo-Murillo, Rodrigo; Cheatham, Thomas E

    2014-12-19

    This unit presents an overview of computer simulation techniques as applied to nucleic acid systems, ranging from simple in vacuo molecular modeling techniques to more complete all-atom molecular dynamics treatments that include an explicit representation of the environment. The third in a series of four units, this unit focuses on critical issues in solvation and the treatment of electrostatics. UNITS 7.5 & 7.8 introduced the modeling of nucleic acid structure at the molecular level. This included a discussion of how to generate an initial model, how to evaluate the utility or reliability of a given model, and ultimately how to manipulate this model to better understand its structure, dynamics, and interactions. Subject to an appropriate representation of the energy, such as a specifically parameterized empirical force field, the techniques of minimization and Monte Carlo simulation, as well as molecular dynamics (MD) methods, were introduced as a way of sampling conformational space for a better understanding of the relevance of a given model. This discussion highlighted the major limitations with modeling in general. When sampling conformational space effectively, difficult issues are encountered, such as multiple minima or conformational sampling problems, and accurately representing the underlying energy of interaction. In order to provide a realistic model of the underlying energetics for nucleic acids in their native environments, it is crucial to include some representation of solvation (by water) and also to properly treat the electrostatic interactions. These subjects are discussed in detail in this unit. Copyright © 2014 John Wiley & Sons, Inc.

  6. Solvation dynamics in N-methylamides

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, C.F.; Fee, R.S.; Maroncelli, M. (Pennsylvania State Univ., University Park (USA))

    1990-06-14

    Solvation times in three homologous amides, N-methylformamide, N-methylacetamide, and N-methylpropionamide, have been detd. from measurements of the dynamic Stokes shift of the fluorescence spectra of two-probe solutes, prodan and coumarin 102. Single-particle reorientation times have also been measured in one of these solvents, N-methylformamide, by using NMR methods. The solvation dynamics are compared to two theoretical models, the simple continuum model and the dynamic MSA model. Although neither model predicts the time dependence of the response satisfactorily, the average solvation times observed are close to the solvent longitudinal relaxation time ({tau}{sub L}) predicted by the simple continuum model. In contrast, the predictions of the dynamical MSA model are approximately 4 times slower than the observed solvation response.

  7. Process algebra modelling styles for biomolecular processes

    OpenAIRE

    Calder, M.; Hillston, J.

    2009-01-01

    We investigate how biomolecular processes are modelled in process algebras, focussing on chemical reactions. We consider various modelling styles and how design decisions made in the definition of the process algebra have an impact on how a modelling style can be applied. Our goal is to highlight the often implicit choices that modellers make in choosing a formalism, and illustrate, through the use of examples, how this can affect expressability as well as the type and complexity of the analy...

  8. NMRbox: A Resource for Biomolecular NMR Computation.

    Science.gov (United States)

    Maciejewski, Mark W; Schuyler, Adam D; Gryk, Michael R; Moraru, Ion I; Romero, Pedro R; Ulrich, Eldon L; Eghbalnia, Hamid R; Livny, Miron; Delaglio, Frank; Hoch, Jeffrey C

    2017-04-25

    Advances in computation have been enabling many recent advances in biomolecular applications of NMR. Due to the wide diversity of applications of NMR, the number and variety of software packages for processing and analyzing NMR data is quite large, with labs relying on dozens, if not hundreds of software packages. Discovery, acquisition, installation, and maintenance of all these packages is a burdensome task. Because the majority of software packages originate in academic labs, persistence of the software is compromised when developers graduate, funding ceases, or investigators turn to other projects. To simplify access to and use of biomolecular NMR software, foster persistence, and enhance reproducibility of computational workflows, we have developed NMRbox, a shared resource for NMR software and computation. NMRbox employs virtualization to provide a comprehensive software environment preconfigured with hundreds of software packages, available as a downloadable virtual machine or as a Platform-as-a-Service supported by a dedicated compute cloud. Ongoing development includes a metadata harvester to regularize, annotate, and preserve workflows and facilitate and enhance data depositions to BioMagResBank, and tools for Bayesian inference to enhance the robustness and extensibility of computational analyses. In addition to facilitating use and preservation of the rich and dynamic software environment for biomolecular NMR, NMRbox fosters the development and deployment of a new class of metasoftware packages. NMRbox is freely available to not-for-profit users. Copyright © 2017 Biophysical Society. All rights reserved.

  9. Ion-Induced Radiation Damage in Biomolecular Systems

    Science.gov (United States)

    Schlathölter, Thomas

    The interaction of keV ions with building blocks of DNA and proteins is of fundamental interest to proton and heavy ion therapy. During the last decade, ion-induced ionization and fragmentation was studied for isolated biomolecules, biomolecular clusters, nanosolvated isolated biomolecules and solid thin biomolecular films. This article gives a brief overview over the research on biomolecular mechanisms underlying ion-induced radiation damage with a focus on the different target systems.

  10. Molecular Reaction Dynamics and Solvation.

    Science.gov (United States)

    Kim, Seong Keun

    A potential energy surface was constructed for the triatomic molecule Li_2H using a semiempirical method akin to the diatomics-in-molecules theory. Valence bond configurations were chosen to include the major ionic contributions in the ground state potential energy. Quasiclassical trajectories were run on this potential energy surface. The results of these calculations are shown to be generally in accord with the experimental investigations of analogous reactions of H atoms with bigger alkali dimer molecules. Certain aspects of chemical reaction dynamics which have been largely overlooked were examined. These involve correlations of vector properties in chemical reactions. Specifically, the strong correlation between orbital and rotational angular momenta in the product channel of this reaction was shown to be the reason for a seemingly contradictory set of distributions of different angles. Gas phase solvation of nucleic acid base molecules was studied using clusters produced by supersonic expansion. Relative stabilities of the species with different numbers of solvent molecules were studied by varying the expansion conditions. The ionization potentials were measured as a function of the number of solvent molecules. Rather distinct effects of hydration were observed for the ionization potentials of adenine and thymine.

  11. Probing volumetric properties of biomolecular systems by pressure perturbation calorimetry (PPC)--the effects of hydration, cosolvents and crowding.

    Science.gov (United States)

    Suladze, Saba; Kahse, Marie; Erwin, Nelli; Tomazic, Daniel; Winter, Roland

    2015-04-01

    Pressure perturbation calorimetry (PPC) is an efficient technique to study the volumetric properties of biomolecules in solution. In PPC, the coefficient of thermal expansion of the partial volume of the biomolecule is deduced from the heat consumed or produced after small isothermal pressure-jumps. The expansion coefficient strongly depends on the interaction of the biomolecule with the solvent or cosolvent as well as on its packing and internal dynamic properties. This technique, complemented with molecular acoustics and densimetry, provides valuable insights into the basic thermodynamic properties of solvation and volume effects accompanying interactions, reactions and phase transitions of biomolecular systems. After outlining the principles of the technique, we present representative examples on protein folding, including effects of cosolvents and crowding, together with a discussion of the interpretation, and further applications. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Scalable Molecular Dynamics for Large Biomolecular Systems

    Directory of Open Access Journals (Sweden)

    Robert K. Brunner

    2000-01-01

    Full Text Available We present an optimized parallelization scheme for molecular dynamics simulations of large biomolecular systems, implemented in the production-quality molecular dynamics program NAMD. With an object-based hybrid force and spatial decomposition scheme, and an aggressive measurement-based predictive load balancing framework, we have attained speeds and speedups that are much higher than any reported in literature so far. The paper first summarizes the broad methodology we are pursuing, and the basic parallelization scheme we used. It then describes the optimizations that were instrumental in increasing performance, and presents performance results on benchmark simulations.

  13. Micro and Nanotechnologies Enhanced Biomolecular Sensing

    Directory of Open Access Journals (Sweden)

    Tza-Huei Wang

    2013-07-01

    Full Text Available This editorial summarizes some of the recent advances of micro and nanotechnology-based tools and devices for biomolecular detection. These include the incorporation of nanomaterials into a sensor surface or directly interfacing with molecular probes to enhance target detection via more rapid and sensitive responses, and the use of self-assembled organic/inorganic nanocomposites that inhibit exceptional spectroscopic properties to enable facile homogenous assays with efficient binding kinetics. Discussions also include some insight into microfluidic principles behind the development of an integrated sample preparation and biosensor platform toward a miniaturized and fully functional system for point of care applications.

  14. Nanoarchitectonics of biomolecular assemblies for functional applications

    Science.gov (United States)

    Avinash, M. B.; Govindaraju, T.

    2014-10-01

    The stringent processes of natural selection and evolution have enabled extraordinary structure-function properties of biomolecules. Specifically, the archetypal designs of biomolecules, such as amino acids, nucleobases, carbohydrates and lipids amongst others, encode unparalleled information, selectivity and specificity. The integration of biomolecules either with functional molecules or with an embodied functionality ensures an eclectic approach for novel and advanced nanotechnological applications ranging from electronics to biomedicine, besides bright prospects in systems chemistry and synthetic biology. Given this intriguing scenario, our feature article intends to shed light on the emerging field of functional biomolecular engineering.

  15. Fundamentos biomoleculares de la diabetes mellitus

    OpenAIRE

    Katiana Mendoza

    2013-01-01

    La diabetes mellitus es una enfermedad endocrina con importantes implicaciones a nivel sistémico, como: angiopatía, neuropatía, retinopatía y nefropatía, entre otras. Estas  complicaciones tienen su origen en eventos biomoleculares desencadenados por la hiperglicemia.  La presente revisión de tema trata sobre la estructura y síntesis de la insulina en las células β del páncreas; los eventos moleculares y bioquímicos que activan su secreción como respuesta a una alta concentración de glucosa e...

  16. Fullerenes in Aromatic Solvents: Correlation between Solvation-Shell Structure, Solvate Formation, and Solubility.

    Science.gov (United States)

    Peerless, James S; Bowers, G Hunter; Kwansa, Albert L; Yingling, Yaroslava G

    2015-12-10

    In this work, an all-atom molecular dynamics simulation technique was employed to gain insight into the dynamic structure of the solvation shell formed around C60 and phenyl-C61-butyric acid methyl ester (PCBM) in nine aromatic solvents. A new method was developed to visualize and quantify the distribution of solvent molecule orientations in the solvation shell. A strong positive correlation was found between the regularity of solvent molecule orientations in the solvation shell and the experimentally obtained solubility limits for both C60 and PCBM. This correlation was extended to predict a solubility of 36 g/L for PCBM in 1,2,4-trimethylbenze. The relationship between solvation-shell structure and solubility provided detailed insight into solvate formation of C60 and solvation in relation to solvent molecular structure and properties. The determined dependence of the solvation-shell structure on the geometric shape of the solvent might allow for enhanced control of fullerene solution-phase behavior during processing by chemically tailoring the solvent molecular structure, potentially diminishing the need for costly and environmentally harmful halogenated solvents and/or additives.

  17. Polymorphs and Versatile Solvates of 7-Hydroxyisoflavone.

    Science.gov (United States)

    Gong, Ningbo; Zhang, Guoshun; Jin, Guimin; Du, Guanhua; Lu, Yang

    2016-04-01

    7-hydroxyisoflavone has been crystallized, identified, and characterized as 2 solvent-free conformational polymorphs and 5 solvates, which differ from each other in the mode of packing and in molecular conformation. All the 7 crystal structures were previously unreported. The conformational polymorphs and solvates were compared by Hirshfeld surface and fingerprint plot analysis and were spectroscopically characterized by powder X-ray diffraction, differential scanning calorimetry, and thermal gravimetric analysis. Hydrogen bond played an important role in the formation of polymorphs. From this study, we can predict that more solvates could be cultivated in other polarity solvents such as isopropanol or 2-butanol at appropriate conditions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. Biomolecular MRI reporters: Evolution of new mechanisms.

    Science.gov (United States)

    Mukherjee, Arnab; Davis, Hunter C; Ramesh, Pradeep; Lu, George J; Shapiro, Mikhail G

    2017-11-01

    Magnetic resonance imaging (MRI) is a powerful technique for observing the function of specific cells and molecules inside living organisms. However, compared to optical microscopy, in which fluorescent protein reporters are available to visualize hundreds of cellular functions ranging from gene expression and chemical signaling to biomechanics, to date relatively few such reporters are available for MRI. Efforts to develop MRI-detectable biomolecules have mainly focused on proteins transporting paramagnetic metals for T1 and T2 relaxation enhancement or containing large numbers of exchangeable protons for chemical exchange saturation transfer. While these pioneering developments established several key uses of biomolecular MRI, such as imaging of gene expression and functional biosensing, they also revealed that low molecular sensitivity poses a major challenge for broader adoption in biology and medicine. Recently, new classes of biomolecular reporters have been developed based on alternative contrast mechanisms, including enhancement of spin diffusivity, interactions with hyperpolarized nuclei, and modulation of blood flow. These novel reporters promise to improve sensitivity and enable new forms of multiplexed and functional imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Solvation dynamics and energetics of intramolecular hydride transfer reactions in biomass conversion.

    Science.gov (United States)

    Mushrif, Samir H; Varghese, Jithin J; Krishnamurthy, Chethana B

    2015-02-21

    Hydride transfer changes the charge structure of the reactant and thus, may induce reorientation/reorganization of solvent molecules. This solvent reorganization may in turn alter the energetics of the reaction. In the present work, we investigate the intramolecular hydride transfer by taking Lewis acid catalyzed glucose to fructose isomerization as an example. The C2-C1 hydride transfer is the rate limiting step in this reaction. Water and methanol are used as solvents and hydride transfer is simulated in the presence of explicit solvent molecules, treated quantum mechanically and at a finite temperature, using Car-Parrinello molecular dynamics (CPMD) and metadynamics. Activation free energy barrier for hydride transfer in methanol is found to be 50 kJ mol(-1) higher than that in water. In contrast, in density functional theory calculations, using an implicit solvent environment, the barriers are almost identical. Analysis of solvent dynamics and electronic polarization along the molecular dynamics trajectory and the results of CPMD-metadynamics simulation of the hydride transfer process in the absence of any solvent suggest that higher barrier in methanol is a result of non-equilibrium solvation. Methanol undergoes electronic polarization during the hydride transfer step. However, its molecular orientational relaxation is a much slower process that takes place after the hydride transfer, over an extended timescale. This results in non-equilibrium solvation. Water, on the other hand, does not undergo significant electronic polarization and thus, has to undergo minimal molecular reorientation to provide near equilibrium solvation to the transition state and an improved equilibrium solvation to the post hydride shift product state. Hence, the hydride transfer step is also observed to be exergonic in water and endergonic in methanol. The aforementioned explanation is juxtaposed to enzyme catalyzed charge transfer reactions, where the enhanced solvation of the

  20. Theory and applications of the generalized Born solvation model in macromolecular simulations.

    Science.gov (United States)

    Tsui, V; Case, D A

    Generalized Born (GB) models provide an attractive way to include some thermodynamic aspects of aqueous solvation into simulations that do not explicitly model the solvent molecules. Here we discuss our recent experience with this model, presenting in detail the way it is implemented and parallelized in the AMBER molecular modeling code. We compare results using the GB model (or GB plus a surface-area based "hydrophobic" term) to explicit solvent simulations for a 10 base-pair DNA oligomer, and for the 108-residue protein thioredoxin. A slight modification of our earlier suggested parameters makes the GB results more like those found in explicit solvent, primarily by slightly increasing the strength of NH [bond] O and NH [bond] N internal hydrogen bonds. Timing and energy stability results are reported, with an eye toward using these model for simulations of larger macromolecular systems and longer time scales. Copyright 2001 John Wiley & Sons, Inc. Biopolymers (Nucleic Acid Sci) 56: 275-291, 2001

  1. Optimal use of data in parallel tempering simulations for the construction of discrete-state Markov models of biomolecular dynamics.

    Science.gov (United States)

    Prinz, Jan-Hendrik; Chodera, John D; Pande, Vijay S; Swope, William C; Smith, Jeremy C; Noé, Frank

    2011-06-28

    Parallel tempering (PT) molecular dynamics simulations have been extensively investigated as a means of efficient sampling of the configurations of biomolecular systems. Recent work has demonstrated how the short physical trajectories generated in PT simulations of biomolecules can be used to construct the Markov models describing biomolecular dynamics at each simulated temperature. While this approach describes the temperature-dependent kinetics, it does not make optimal use of all available PT data, instead estimating the rates at a given temperature using only data from that temperature. This can be problematic, as some relevant transitions or states may not be sufficiently sampled at the temperature of interest, but might be readily sampled at nearby temperatures. Further, the comparison of temperature-dependent properties can suffer from the false assumption that data collected from different temperatures are uncorrelated. We propose here a strategy in which, by a simple modification of the PT protocol, the harvested trajectories can be reweighted, permitting data from all temperatures to contribute to the estimated kinetic model. The method reduces the statistical uncertainty in the kinetic model relative to the single temperature approach and provides estimates of transition probabilities even for transitions not observed at the temperature of interest. Further, the method allows the kinetics to be estimated at temperatures other than those at which simulations were run. We illustrate this method by applying it to the generation of a Markov model of the conformational dynamics of the solvated terminally blocked alanine peptide.

  2. A unified perspective on preferential solvation and adsorption based on inhomogeneous solvation theory

    Science.gov (United States)

    Shimizu, Seishi; Matubayasi, Nobuyuki

    2018-02-01

    How cosolvents affects solvation has been revealed through the independent determination of solute-solvent and solute-cosolvent interactions guaranteed by the phase rule. Based on the first principles of inhomogeneous solvation theory, we present here a general matrix theory encompassing both preferential solvation and surface adsorption. The central role of the stability conditions, that govern how many excess numbers (surface excesses) are independently determinable, have been clarified from the first principles. The advantage of the inhomogeneous approach has been demonstrated to be in its ease in treating solvation and adsorption in a unified manner, while its disadvantage, for example in membrane dialysis experiments, can be overcome by the inhomogeneous-homogeneous conversion.

  3. ULTRAFAST ELECTRONIC FLUCTUATION AND SOLVATION IN LIQUIDS

    NARCIS (Netherlands)

    NIBBERING, ETJ; WIERSMA, DA; DUPPEN, K; Nibbering, Erik T.J.

    1994-01-01

    Solvation and optical dephasing of electronic transitions in molecular liquids are studied over a large range of time scales. It is shown that these optical effects, which are due to coupling of the electronic degrees of freedom with the nuclear motion in the liquid, are closely connected. The

  4. Experimental and computational studies of polar solvation

    Energy Technology Data Exchange (ETDEWEB)

    1991-01-01

    Many articles and papers were published; a few are still in preparation or will be published. The solvation dynamics studies will be extended to ionic solutions. Computer simulations were also performed. A new line of research was begun on excited-state proton-transfer reactions catalyzed by alcohol solvents. (DLC)

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

    Directory of Open Access Journals (Sweden)

    Kari Gaalswyk

    2016-05-01

    Full Text Available 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.

  6. Guanidinium-based "molecular glues" for modulation of biomolecular functions.

    Science.gov (United States)

    Mogaki, Rina; Hashim, P K; Okuro, Kou; Aida, Takuzo

    2017-10-30

    Molecular adhesion based on multivalent interactions plays essential roles in various biological processes. Hence, "molecular glues" that can adhere to biomolecules may modulate biomolecular functions and therefore can be applied to therapeutics. This tutorial review describes design strategies for developing adhesive motifs for biomolecules based on multivalent interactions. We highlight a guanidinium ion-based salt-bridge as a key interaction for adhesion to biomolecules and discuss the application of molecular glues for manipulation of biomolecular assemblies, drug delivery systems, and modulation of biomolecular functions.

  7. Micro- and nanodevices integrated with biomolecular probes.

    Science.gov (United States)

    Alapan, Yunus; Icoz, Kutay; Gurkan, Umut A

    2015-12-01

    Understanding how biomolecules, proteins and cells interact with their surroundings and other biological entities has become the fundamental design criterion for most biomedical micro- and nanodevices. Advances in biology, medicine, and nanofabrication technologies complement each other and allow us to engineer new tools based on biomolecules utilized as probes. Engineered micro/nanosystems and biomolecules in nature have remarkably robust compatibility in terms of function, size, and physical properties. This article presents the state of the art in micro- and nanoscale devices designed and fabricated with biomolecular probes as their vital constituents. General design and fabrication concepts are presented and three major platform technologies are highlighted: microcantilevers, micro/nanopillars, and microfluidics. Overview of each technology, typical fabrication details, and application areas are presented by emphasizing significant achievements, current challenges, and future opportunities. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Semisynthetic and Biomolecular Hydrogen Evolution Catalysts.

    Science.gov (United States)

    Kandemir, Banu; Chakraborty, Saikat; Guo, Yixing; Bren, Kara L

    2016-01-19

    There has been great interest in the development of stable, inexpensive, efficient catalysts capable of reducing aqueous protons to hydrogen (H2), an alternative to fossil fuels. While synthetic H2 evolution catalysts have been in development for decades, recently there has been great progress in engineering biomolecular catalysts and assemblies of synthetic catalysts and biomolecules. In this Forum Article, progress in engineering proteins to catalyze H2 evolution from water is discussed. The artificial enzymes described include assemblies of synthetic catalysts and photosynthetic proteins, proteins with cofactors replaced with synthetic catalysts, and derivatives of electron-transfer proteins. In addition, a new catalyst consisting of a thermophilic cobalt-substituted cytochrome c is reported. As an electrocatalyst, the cobalt cytochrome shows nearly quantitative Faradaic efficiency and excellent longevity with a turnover number of >270000.

  9. Enhanced sampling techniques in biomolecular simulations.

    Science.gov (United States)

    Spiwok, Vojtech; Sucur, Zoran; Hosek, Petr

    2015-11-01

    Biomolecular simulations are routinely used in biochemistry and molecular biology research; however, they often fail to match expectations of their impact on pharmaceutical and biotech industry. This is caused by the fact that a vast amount of computer time is required to simulate short episodes from the life of biomolecules. Several approaches have been developed to overcome this obstacle, including application of massively parallel and special purpose computers or non-conventional hardware. Methodological approaches are represented by coarse-grained models and enhanced sampling techniques. These techniques can show how the studied system behaves in long time-scales on the basis of relatively short simulations. This review presents an overview of new simulation approaches, the theory behind enhanced sampling methods and success stories of their applications with a direct impact on biotechnology or drug design. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Micro- and nanodevices integrated with biomolecular probes

    Science.gov (United States)

    Alapan, Yunus; Icoz, Kutay; Gurkan, Umut A.

    2016-01-01

    Understanding how biomolecules, proteins and cells interact with their surroundings and other biological entities has become the fundamental design criterion for most biomedical micro- and nanodevices. Advances in biology, medicine, and nanofabrication technologies complement each other and allow us to engineer new tools based on biomolecules utilized as probes. Engineered micro/nanosystems and biomolecules in nature have remarkably robust compatibility in terms of function, size, and physical properties. This article presents the state of the art in micro- and nanoscale devices designed and fabricated with biomolecular probes as their vital constituents. General design and fabrication concepts are presented and three major platform technologies are highlighted: microcantilevers, micro/nanopillars, and microfluidics. Overview of each technology, typical fabrication details, and application areas are presented by emphasizing significant achievements, current challenges, and future opportunities. PMID:26363089

  11. Biomolecular Markers in Cancer of the Tongue

    Directory of Open Access Journals (Sweden)

    Daris Ferrari

    2009-01-01

    Full Text Available The incidence of tongue cancer is increasing worldwide, and its aggressiveness remains high regardless of treatment. Genetic changes and the expression of abnormal proteins have been frequently reported in the case of head and neck cancers, but the little information that has been published concerning tongue tumours is often contradictory. This review will concentrate on the immunohistochemical expression of biomolecular markers and their relationships with clinical behaviour and prognosis. Most of these proteins are associated with nodal stage, tumour progression and metastases, but there is still controversy concerning their impact on disease-free and overall survival, and treatment response. More extensive clinical studies are needed to identify the patterns of molecular alterations and the most reliable predictors in order to develop tailored anti-tumour strategies based on the targeting of hypoxia markers, vascular and lymphangiogenic factors, epidermal growth factor receptors, intracytoplasmatic signalling and apoptosis.

  12. Fundamentos biomoleculares de la diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Katiana Mendoza

    2013-12-01

    Full Text Available La diabetes mellitus es una enfermedad endocrina con importantes implicaciones a nivel sistémico, como: angiopatía, neuropatía, retinopatía y nefropatía, entre otras. Estas  complicaciones tienen su origen en eventos biomoleculares desencadenados por la hiperglicemia.  La presente revisión de tema trata sobre la estructura y síntesis de la insulina en las células β del páncreas; los eventos moleculares y bioquímicos que activan su secreción como respuesta a una alta concentración de glucosa en sangre; la cascada de señalización generada por la unión de la insulina a su receptor sobre células diana; y las alteraciones metabólicas que los diferentes tipos de diabetes mellitus producen.

  13. Interacting with the biomolecular solvent accessible surface via a haptic feedback device

    Directory of Open Access Journals (Sweden)

    Hayward Steven

    2009-10-01

    Full Text Available Abstract Background From the 1950s computer based renderings of molecules have been produced to aid researchers in their understanding of biomolecular structure and function. A major consideration for any molecular graphics software is the ability to visualise the three dimensional structure of the molecule. Traditionally, this was accomplished via stereoscopic pairs of images and later realised with three dimensional display technologies. Using a haptic feedback device in combination with molecular graphics has the potential to enhance three dimensional visualisation. Although haptic feedback devices have been used to feel the interaction forces during molecular docking they have not been used explicitly as an aid to visualisation. Results A haptic rendering application for biomolecular visualisation has been developed that allows the user to gain three-dimensional awareness of the shape of a biomolecule. By using a water molecule as the probe, modelled as an oxygen atom having hard-sphere interactions with the biomolecule, the process of exploration has the further benefit of being able to determine regions on the molecular surface that are accessible to the solvent. This gives insight into how awkward it is for a water molecule to gain access to or escape from channels and cavities, indicating possible entropic bottlenecks. In the case of liver alcohol dehydrogenase bound to the inhibitor SAD, it was found that there is a channel just wide enough for a single water molecule to pass through. Placing the probe coincident with crystallographic water molecules suggests that they are sometimes located within small pockets that provide a sterically stable environment irrespective of hydrogen bonding considerations. Conclusion By using the software, named HaptiMol ISAS (available from http://www.haptimol.co.uk, one can explore the accessible surface of biomolecules using a three-dimensional input device to gain insights into the shape and water

  14. The Aqueous Solvation of Water A Comparison of Continuum Methods with Molecular Dynamics

    CERN Document Server

    Rick, S W; Rick, Steven W.

    1994-01-01

    The calculation of the solvation properties of a single water molecule in liquid water is carried out in two ways. In the first, the water molecule is placed in a cavity and the solvent is treated as a dielectric continuum. This model is analyzed by numerically solving the Poisson equation using the DelPhi program. The resulting solvation properties depend sensitively on the shape and size of the cavity. In the second method, the solvent and solute molecules are treated explicitly in molecular dynamics simulations using Ewald boundary conditions. We find a 2 kcal/mole difference in solvation free energies predicted by these two methods when standard cavity radii are used. In addition, dielectric continuum theory assumes that the solvent reacts solely by realigning its electric moments linearly with the strength of the solute's electric field; the results of the molecular simulation show important non-linear effects. Non-linear solvent effects are generally of two types: dielectric saturation, due to solvent-s...

  15. Parameter optimization in differential geometry based solvation models.

    Science.gov (United States)

    Wang, Bao; Wei, G W

    2015-10-07

    Differential geometry (DG) based solvation models are a new class of variational implicit solvent approaches that are able to avoid unphysical solvent-solute boundary definitions and associated geometric singularities, and dynamically couple polar and non-polar interactions in a self-consistent framework. Our earlier study indicates that DG based non-polar solvation model outperforms other methods in non-polar solvation energy predictions. However, the DG based full solvation model has not shown its superiority in solvation analysis, due to its difficulty in parametrization, which must ensure the stability of the solution of strongly coupled nonlinear Laplace-Beltrami and Poisson-Boltzmann equations. In this work, we introduce new parameter learning algorithms based on perturbation and convex optimization theories to stabilize the numerical solution and thus achieve an optimal parametrization of the DG based solvation models. An interesting feature of the present DG based solvation model is that it provides accurate solvation free energy predictions for both polar and non-polar molecules in a unified formulation. Extensive numerical experiment demonstrates that the present DG based solvation model delivers some of the most accurate predictions of the solvation free energies for a large number of molecules.

  16. DNA algorithms of implementing biomolecular databases on a biological computer.

    Science.gov (United States)

    Chang, Weng-Long; Vasilakos, Athanasios V

    2015-01-01

    In this paper, DNA algorithms are proposed to perform eight operations of relational algebra (calculus), which include Cartesian product, union, set difference, selection, projection, intersection, join, and division, on biomolecular relational databases.

  17. Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems

    Energy Technology Data Exchange (ETDEWEB)

    Radak, Brian K. [Leadership; Chipot, Christophe [Laboratoire; Department; Suh, Donghyuk [Department; Jo, Sunhwan [Leadership; Jiang, Wei [Leadership; Phillips, James C. [Theoretical; Schulten, Klaus [Department; Theoretical; Roux, Benoît [Department; Department; Center for

    2017-11-22

    An increasingly important endeavor is to develop computational strategies that enable molecular dynamics (MD) simulations of biomolecular systems with spontaneous changes in protonation states under conditions of constant pH. The present work describes our efforts to implement the powerful constant-pH MD simulation method, based on a hybrid nonequilibrium MD/Monte Carlo (neMD/MC) technique within the highly scalable program NAMD. The constant-pH hybrid neMD/MC method has several appealing features; it samples the correct semigrand canonical ensemble rigorously, the computational cost increases linearly with the number of titratable sites, and it is applicable to explicit solvent simulations. The present implementation of the constant-pH hybrid neMD/MC in NAMD is designed to handle a wide range of biomolecular systems with no constraints on the choice of force field. Furthermore, the sampling efficiency can be adaptively improved on-the-fly by adjusting algorithmic parameters during the simulation. Illustrative examples emphasizing medium- and large-scale applications on next-generation supercomputing architectures are provided.

  18. A new approach to implement absorbing boundary condition in biomolecular electrostatics.

    Science.gov (United States)

    Goni, Md Osman

    2013-01-01

    This paper discusses a novel approach to employ the absorbing boundary condition in conjunction with the finite-element method (FEM) in biomolecular electrostatics. The introduction of Bayliss-Turkel absorbing boundary operators in electromagnetic scattering problem has been incorporated by few researchers. However, in the area of biomolecular electrostatics, this boundary condition has not been investigated yet. The objective of this paper is twofold. First, to solve nonlinear Poisson-Boltzmann equation using Newton's method and second, to find an efficient and acceptable solution with minimum number of unknowns. In this work, a Galerkin finite-element formulation is used along with a Bayliss-Turkel absorbing boundary operator that explicitly accounts for the open field problem by mapping the Sommerfeld radiation condition from the far field to near field. While the Bayliss-Turkel condition works well when the artificial boundary is far from the scatterer, an acceptable tolerance of error can be achieved with the second order operator. Numerical results on test case with simple sphere show that the treatment is able to reach the same level of accuracy achieved by the analytical method while using a lower grid density. Bayliss-Turkel absorbing boundary condition (BTABC) combined with the FEM converges to the exact solution of scattering problems to within discretization error.

  19. Simulated solvation of organic ions: protonated methylamines in water nanodroplets. Convergence toward bulk properties and the absolute proton solvation enthalpy.

    Science.gov (United States)

    Houriez, Céline; Meot-Ner Mautner, Michael; Masella, Michel

    2014-06-12

    We applied an alternative, purely theoretical route to estimate thermodynamical properties of organic ions in bulk solution. The method performs a large ensemble of simulations of ions solvated in water nanodroplets of different sizes, using a polarizable molecular dynamics approach. We consider protonated ammonia and methylamines, and K(+) for comparison, solvated in droplets of 50-1000 water molecules. The parameters of the model are assigned from high level quantum computations of small clusters. All the bulk phase results extrapolated from droplet simulations match, and confirm independently, the relative and absolute experiment-based ion solvation energies. Without using experiment-based parameters or assumptions, the results confirm independently the solvation enthalpy of the proton, as -270.3 ± 1.1 kcal mol(-1). The calculated relative solvation enthalpies of these ions are constant from small water clusters, where only the ionic headgroups are solvated, up to bulk solution. This agrees with experimental thermochemistry, that the relative solvation energies of alkylammonium ions by only four H2O molecules reproduce the relative bulk solvation energies, although the small clusters lack major bulk solvation factors. The droplet results also show a slow convergence of ion solvation properties toward their bulk limit, and predict that the stepwise solvation enthalpies of ion/water droplets are very close to those of pure neutral water droplets already after 50 water molecules. Both the ionic and neutral clusters approach the bulk condensation energy very gradually up to 10,000 water molecules, consistent with the macroscopic liquid drop model for pure water droplets. Compared to standard computational methods based on infinite periodic systems, our protocol represents a new purely theoretical approach to investigate the solvation properties of ions. It is applicable to the solvation of organic ions, which are pivotal in environmental, industrial, and

  20. Preferential Solvation of an Asymmetric Redox Molecule

    Energy Technology Data Exchange (ETDEWEB)

    Han, Kee Sung; Rajput, Nav Nidhi; Vijayakumar, M.; Wei, Xiaoliang; Wang, Wei; Hu, Jian Z.; Persson, Kristin A.; Mueller, Karl T.

    2016-12-15

    The fundamental correlations between inter-molecular interactions, solvation structure and functionality of electrolytes are in many cases unknown, particularly for multi-component liquid systems. In this work, we explore such correlations by investigating the complex interplay between solubility and solvation structure for the electrolyte system comprising N-(ferrocenylmethyl)-N,N-dimethyl-N-ethylammonium bistrifluoromethylsulfonimide (Fc1N112-TFSI) dissolved in a ternary carbonate solvent mixture using combined NMR relaxation and computational analyses. Probing the evolution of the solvent-solvent, ion-solvent and ion-ion interactions with an increase in solute concentration provides a molecular level understanding of the solubility limit of the Fc1N112-TFSI system. An increase in solute con-centration leads to pronounced Fc1N112-TFSI contact-ion pair formation by diminishing solvent-solvent and ion-solvent type interactions. At the solubility limit, the precipitation of solute is initiated through agglomeration of contact-ion pairs due to overlapping solvation shells.

  1. Extension of the FACTS Implicit Solvation Model to Membranes.

    Science.gov (United States)

    Carballo-Pacheco, Martín; Vancea, Ioan; Strodel, Birgit

    2014-08-12

    The generalized Born (GB) formalism can be used to model water as a dielectric continuum. Among the different implicit solvent models using the GB formalism, FACTS is one of the fastest. Here, we extend FACTS so that it can represent a membrane environment. This extension is accomplished by considering a position dependent dielectric constant and empirical surface tension parameter. For the calculation of the effective Born radii in different dielectric environments we present a parameter-free approximation to Kirkwood's equation, which uses the Born radii obtained with FACTS for the water environment as input. This approximation is tested for the calculation of self-free energies, pairwise interaction energies in solution and solvation free energies of complete protein conformations. The results compare well to those from the finite difference Poisson method. The new implicit membrane model is applied to estimate free energy insertion profiles of amino acid analogues and in molecular dynamics simulations of melittin, WALP23 and KALP23, glycophorin A, bacteriorhodopsin, and a Clc channel dimer. In all cases, the results agree qualitatively with experiments and explicit solvent simulations. Moreover, the implicit membrane model is only six times slower than a vacuum simulation.

  2. NMR studies of dynamic biomolecular conformational ensembles.

    Science.gov (United States)

    Torchia, Dennis A

    2015-02-01

    Multidimensional heteronuclear NMR approaches can provide nearly complete sequential signal assignments of isotopically enriched biomolecules. The availability of assignments together with measurements of spin relaxation rates, residual spin interactions, J-couplings and chemical shifts provides information at atomic resolution about internal dynamics on timescales ranging from ps to ms, both in solution and in the solid state. However, due to the complexity of biomolecules, it is not possible to extract a unique atomic-resolution description of biomolecular motions even from extensive NMR data when many conformations are sampled on multiple timescales. For this reason, powerful computational approaches are increasingly applied to large NMR data sets to elucidate conformational ensembles sampled by biomolecules. In the past decade, considerable attention has been directed at an important class of biomolecules that function by binding to a wide variety of target molecules. Questions of current interest are: "Does the free biomolecule sample a conformational ensemble that encompasses the conformations found when it binds to various targets; and if so, on what time scale is the ensemble sampled?" This article reviews recent efforts to answer these questions, with a focus on comparing ensembles obtained for the same biomolecules by different investigators. A detailed comparison of results obtained is provided for three biomolecules: ubiquitin, calmodulin and the HIV-1 trans-activation response RNA. Published by Elsevier B.V.

  3. Epigenetic molecular recognition: a biomolecular modeling perspective.

    Science.gov (United States)

    Vellore, Nadeem A; Baron, Riccardo

    2014-03-01

    The abnormal regulation of epigenetic protein families is associated with the onset and progression of various human diseases. However, epigenetic processes remain relatively obscure at the molecular level, thus preventing the rational design of chemical therapeutics. An array of robust computational and modeling approaches can complement experiments to shed light on the complex mechanisms of epigenetic molecular recognition and can guide medicinal chemists in designing selective and potent drug molecules. Herein we present a review of studies focused on epigenetic molecular recognition from a biomolecular modeling viewpoint. Although the known epigenetic targets are numerous, this review focuses on the more limited protein families on which computational modeling has been successfully applied. Therefore, we review three main topics: 1) histone deacetylases, 2) histone demethylases, and 3) histone tail dynamics. A brief review of the biological background and biomedical relevance is presented for each topic, followed by a detailed discussion of the computational studies and their relevance. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Spectroscopy of mobility-selected biomolecular ions.

    Science.gov (United States)

    Papadopoulos, Georgios; Svendsen, Annette; Boyarkin, Oleg V; Rizzo, Thomas R

    2011-01-01

    We describe here experiments that combine differential ion mobility, which separates conformational isomers of biomolecular ions, with electronic spectroscopy in a cold, radio-frequency ion trap. Although the low temperature attainable in a cold ion trap greatly simplifies the electronic spectra of large molecules, conformational heterogeneity can still be a significant source of congestion, complicating spectroscopic analysis. We demonstrate here that using differential ion mobility to separate gas-phase peptide conformers before injecting them into a cold ion trap allows one to decompose a dense spectrum into contributions from different conformational families. In the inverse sense, cold ion spectroscopy can be used as a conformation-specific detector for ion mobility, allowing one to separate an unresolved peak into contributions from different conformational families. The doubly protonated peptide bradykinin serves as a good test case for the marriage of these two techniques as it exhibits a considerable degree of conformational heterogeneity that results in a highly congested electronic spectrum. Our results demonstrate the feasibility and advantages of directly coupling ion mobility with spectroscopy and provide a diagnostic of conformational isomerization of this peptide after being produced in the gas phase by electrospray.

  5. A multiscale modeling approach for biomolecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Bowling, Alan, E-mail: bowling@uta.edu; Haghshenas-Jaryani, Mahdi, E-mail: mahdi.haghshenasjaryani@mavs.uta.edu [The University of Texas at Arlington, Department of Mechanical and Aerospace Engineering (United States)

    2015-04-15

    This paper presents a new multiscale molecular dynamic model for investigating the effects of external interactions, such as contact and impact, during stepping and docking of motor proteins and other biomolecular systems. The model retains the mass properties ensuring that the result satisfies Newton’s second law. This idea is presented using a simple particle model to facilitate discussion of the rigid body model; however, the particle model does provide insights into particle dynamics at the nanoscale. The resulting three-dimensional model predicts a significant decrease in the effect of the random forces associated with Brownian motion. This conclusion runs contrary to the widely accepted notion that the motor protein’s movements are primarily the result of thermal effects. This work focuses on the mechanical aspects of protein locomotion; the effect ATP hydrolysis is estimated as internal forces acting on the mechanical model. In addition, the proposed model can be numerically integrated in a reasonable amount of time. Herein, the differences between the motion predicted by the old and new modeling approaches are compared using a simplified model of myosin V.

  6. Making the Tacit Explicit

    DEFF Research Database (Denmark)

    Blasco, Maribel

    2015-01-01

    The article proposes an approach, broadly inspired by culturally inclusive pedagogy, to facilitate international student academic adaptation based on rendering tacit aspects of local learning cultures explicit to international full degree students, rather than adapting them. Preliminary findings...... are presented from a focus group-based exploratory study of international student experiences at different stages of their studies at a Danish business school, one of Denmark’s most international universities. The data show how a major source of confusion for these students has to do with the tacit logics...... and expectations that shape how the formal steps of the learning cycle are understood and enacted locally, notably how learning and assessment moments are defined and related to one another. Theoretically, the article draws on tacit knowledge and sense-making theories to analyse student narratives...

  7. Preferential Solvation of Lithium Cations and Impacts on Oxygen Reduction in Lithium-Air Batteries.

    Science.gov (United States)

    Zheng, Dong; Qu, Deyu; Yang, Xiao-Qing; Lee, Hung-Sui; Qu, Deyang

    2015-09-16

    The solvation of Li+ with 11 nonaqueous solvents commonly used as electrolytes for lithium batteries was studied. The solvation preferences of different solvents were compared by means of electrospray mass spectrometry and collision-induced dissociation. The relative strength of the solvent for the solvation of Li+ was determined. The Lewis acidity of the solvated Li+ cations was determined by the preferential solvation of the solvent in the solvation shell. The kinetics of the catalytic disproportionation of the O2•- depends on the relative Lewis acidity of the solvated Li+ ion. The impact of the solvated Li+ cation on the O2 redox reaction was also investigated.

  8. High quality NMR structures: a new force field with implicit water and membrane solvation for Xplor-NIH

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Ye [Sanford-Burnham-Prebys Medical Discovery Institute (United States); Schwieters, Charles D. [National Institutes of Health, Center for Information Technology (United States); Opella, Stanley J. [University of California San Diego, Department of Chemistry and Biochemistry (United States); Marassi, Francesca M., E-mail: fmarassi@sbmri.org [Sanford-Burnham-Prebys Medical Discovery Institute (United States)

    2017-01-15

    Structure determination of proteins by NMR is unique in its ability to measure restraints, very accurately, in environments and under conditions that closely mimic those encountered in vivo. For example, advances in solid-state NMR methods enable structure determination of membrane proteins in detergent-free lipid bilayers, and of large soluble proteins prepared by sedimentation, while parallel advances in solution NMR methods and optimization of detergent-free lipid nanodiscs are rapidly pushing the envelope of the size limit for both soluble and membrane proteins. These experimental advantages, however, are partially squandered during structure calculation, because the commonly used force fields are purely repulsive and neglect solvation, Van der Waals forces and electrostatic energy. Here we describe a new force field, and updated energy functions, for protein structure calculations with EEFx implicit solvation, electrostatics, and Van der Waals Lennard-Jones forces, in the widely used program Xplor-NIH. The new force field is based primarily on CHARMM22, facilitating calculations with a wider range of biomolecules. The new EEFx energy function has been rewritten to enable OpenMP parallelism, and optimized to enhance computation efficiency. It implements solvation, electrostatics, and Van der Waals energy terms together, thus ensuring more consistent and efficient computation of the complete nonbonded energy lists. Updates in the related python module allow detailed analysis of the interaction energies and associated parameters. The new force field and energy function work with both soluble proteins and membrane proteins, including those with cofactors or engineered tags, and are very effective in situations where there are sparse experimental restraints. Results obtained for NMR-restrained calculations with a set of five soluble proteins and five membrane proteins show that structures calculated with EEFx have significant improvements in accuracy, precision

  9. Biomolecular Modification of Inorganic Crystal Growth

    Energy Technology Data Exchange (ETDEWEB)

    De Yoreo, J J

    2007-04-27

    The fascinating shapes and hierarchical designs of biomineralized structures are an inspiration to materials scientists because of the potential they suggest for biomolecular control over materials synthesis. Conversely, the failure to prevent or limit tissue mineralization in the vascular, skeletal, and urinary systems is a common source of disease. Understanding the mechanisms by which organisms direct or limit crystallization has long been a central challenge to the biomineralization community. One prevailing view is that mineral-associated macromolecules are responsible for either inhibiting crystallization or initiating and stabilizing non-equilibrium crystal polymorphs and morphologies through interactions between anionic moieties and cations in solution or at mineralizing surfaces. In particular, biomolecules that present carboxyl groups to the growing crystal have been implicated as primary modulators of growth. Here we review the results from a combination of in situ atomic force microscopy (AFM) and molecular modeling (MM) studies to investigate the effect of specific interactions between carboxylate-rich biomolecules and atomic steps on crystal surfaces during the growth of carbonates, oxalates and phosphates of calcium. Specifically, we how the growth kinetics and morphology depend on the concentration of additives that include citrate, simple amino acids, synthetic Asp-rich polypeptides, and naturally occurring Asp-rich proteins found in both functional and pathological mineral tissues. The results reveal a consistent picture of shape modification in which stereochemical matching of modifiers to specific atomic steps drives shape modification. Inhibition and other changes in growth kinetics are shown to be due to a range of mechanisms that depend on chemistry and molecular size. Some effects are well described by classic crystal growth theories, but others, such as step acceleration due to peptide charge and hydrophylicity, were previously unrealized

  10. A universal approach to solvation modeling.

    Science.gov (United States)

    Cramer, Christopher J; Truhlar, Donald G

    2008-06-01

    Continuum mean-field models that have been carefully designed to address the various electrostatic and nonelectrostatic interactions that develop between a molecule and a surrounding medium are particularly efficient tools for studying the effects of condensed phases on molecular structure, energetics, properties, spectra, interaction potentials, and dynamics. The SM8 model may be combined with density functional theory or Hartree-Fock theory to describe a solute's electronic structure and its self-consistent-field polarization by a solvent. A key feature is the use of class IV charge models to obtain accurate charge distributions (either in the vapor phase or in solution), even when using small basis sets that are affordable for large systems. A second key feature is that nonelectrostatic effects due to cavity formation, dispersion interactions, and changes in solvent structure are included in terms of empirical atomic surface tensions that depend on geometry but do not require atom-type assignments by the user. Use of an analytic surface area algorithm provides very stable energy gradients that allow geometry optimization in solution. The SM8 continuum model, the culmination of a series of SMx models (x = 1-8), permits the modeling of such diverse media as aqueous and organic solvents, soils, lipid bilayers, and air-water interfaces. In addition to predicting accurate transfer free energies between gaseous and condensed phases or between two different condensed phases, SMx models have been useful for predicting the significant influence of condensed phases on processes associated with a change in molecular charge, including acid/base equilibria and oxidation/reduction processes. In this Account, we provide an overview of the algorithms associated with the computation of free energies of solvation in the SM8 model. We also compare the accuracies of the SM8 model with those of other continuum solvation models. Finally, we highlight applications of the SM8 models to

  11. Comparison between implicit and hybrid solvation methods for the ...

    Indian Academy of Sciences (India)

    Both implicit solvation method (dielectric polarizable continuum model, DPCM) and hybrid solvation method (cluster-continuum model) were adopted to calculate the of mono-protonated form of 132-(demethoxycarbonyl) pheophytin (Pheo) in methanol. In the cluster-continuum model calculations, we considered ...

  12. Abacavir methanol 2.5-solvate

    Directory of Open Access Journals (Sweden)

    Phuong-Truc T. Pham

    2009-08-01

    Full Text Available The structure of abacavir (systematic name: {(1S,4R-4-[2-amino-6-(cyclopropylamino-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol, C14H18N6O·2.5CH3OH, consists of hydrogen-bonded ribbons which are further held together by additional hydrogen bonds involving the hydroxyl group and two N atoms on an adjacent purine. The asymmetric unit also contains 2.5 molecules of methanol solvate which were grossly disordered and were excluded using SQUEEZE subroutine in PLATON [Spek, (2009. Acta Cryst. D65, 148–155].

  13. A mechanical Turing machine: blueprint for a biomolecular computer.

    Science.gov (United States)

    Shapiro, Ehud

    2012-08-06

    We describe a working mechanical device that embodies the theoretical computing machine of Alan Turing, and as such is a universal programmable computer. The device operates on three-dimensional building blocks by applying mechanical analogues of polymer elongation, cleavage and ligation, movement along a polymer, and control by molecular recognition unleashing allosteric conformational changes. Logically, the device is not more complicated than biomolecular machines of the living cell, and all its operations are part of the standard repertoire of these machines; hence, a biomolecular embodiment of the device is not infeasible. If implemented, such a biomolecular device may operate in vivo, interacting with its biochemical environment in a program-controlled manner. In particular, it may 'compute' synthetic biopolymers and release them into its environment in response to input from the environment, a capability that may have broad pharmaceutical and biological applications.

  14. Organization and Function of Non-dynamic Biomolecular Condensates.

    Science.gov (United States)

    Woodruff, Jeffrey B; Hyman, Anthony A; Boke, Elvan

    2017-12-16

    Cells compartmentalize biochemical reactions using organelles. Organelles can be either membrane-bound compartments or supramolecular assemblies of protein and ribonucleic acid known as 'biomolecular condensates'. Biomolecular condensates, such as nucleoli and germ granules, have been described as liquid like, as they have the ability to fuse, flow, and undergo fission. Recent experiments have revealed that some liquid-like condensates can mature over time to form stable gels. In other cases, biomolecular condensates solidify into amyloid-like fibers. Here we discuss the assembly, organization, and physiological roles of these more stable condensates in cells, focusing on Balbiani bodies, centrosomes, nuclear pores, and amyloid bodies. We discuss how the material properties of these condensates can be explained by the principles of liquid-liquid phase separation and maturation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. An analytical approach to computing biomolecular electrostatic potential. II. Validation and applications

    Science.gov (United States)

    Gordon, John C.; Fenley, Andrew T.; Onufriev, Alexey

    2008-08-01

    An ability to efficiently compute the electrostatic potential produced by molecular charge distributions under realistic solvation conditions is essential for a variety of applications. Here, the simple closed-form analytical approximation to the Poisson equation rigorously derived in Part I for idealized spherical geometry is tested on realistic shapes. The effects of mobile ions are included at the Debye-Hückel level. The accuracy of the resulting closed-form expressions for electrostatic potential is assessed through comparisons with numerical Poisson-Boltzmann (NPB) reference solutions on a test set of 580 representative biomolecular structures under typical conditions of aqueous solvation. For each structure, the deviation from the reference is computed for a large number of test points placed near the dielectric boundary (molecular surface). The accuracy of the approximation, averaged over all test points in each structure, is within 0.6 kcal/mol/|e|~kT per unit charge for all structures in the test set. For 91.5% of the individual test points, the deviation from the NPB potential is within 0.6 kcal/mol/|e|. The deviations from the reference decrease with increasing distance from the dielectric boundary: The approximation is asymptotically exact far away from the source charges. Deviation of the overall shape of a structure from ideal spherical does not, by itself, appear to necessitate decreased accuracy of the approximation. The largest deviations from the NPB reference are found inside very deep and narrow indentations that occur on the dielectric boundaries of some structures. The dimensions of these pockets of locally highly negative curvature are comparable to the size of a water molecule; the applicability of a continuum dielectric models in these regions is discussed. The maximum deviations from the NPB are reduced substantially when the boundary is smoothed by using a larger probe radius (3 A˚) to generate the molecular surface. A detailed accuracy

  16. Solvation of polymers as mutual association. II. Basic thermodynamic properties.

    Science.gov (United States)

    Dudowicz, Jacek; Freed, Karl F; Douglas, Jack F

    2013-04-28

    The theory of equilibrium solvation of polymers B by a relatively low molar mass solvent A, developed in the simplest form in Paper I, is used to explore some essential trends in basic thermodynamic properties of solvated polymer solutions, such as the equilibrium concentrations of solvated polymers AiB and free solvent molecules A, the mass distribution φ(AiB)(i) of solvated clusters, the extent of solvation of the polymer Φ(solv), the solvation transition lines T(solv)(φB(o)), the specific heat C(V), the osmotic second virial coefficient B2, phase stability boundaries, and the critical temperatures associated with closed loop phase diagrams. We discuss the differences between the basic thermodynamic properties of solvated polymers and those derived previously for hierarchical mutual association processes involving the association of two different species A and B into AB complexes and the subsequent polymerization of these AB complexes into linear polymeric structures. The properties of solvated polymer solutions are also compared to those for solutions of polymers in a self-associating solvent. Closed loop phase diagrams for solvated polymer solutions arise in the theory from the competition between the associative and van der Waals interactions, a behavior also typical for dispersed molecular and nanoparticle species that strongly associate with the host fluid. Our analysis of the temperature dependence of the second osmotic virial coefficient reveals that the theory must be generalized to describe the association of multiple solvent molecules with each chain monomer, and this complex extension of the present model will be developed in subsequent papers aimed at a quantitative rather than qualitative treatment of solvated polymer solutions.

  17. Laser photodissociation and spectroscopy of mass-separated biomolecular ions

    CERN Document Server

    Polfer, Nicolas C

    2014-01-01

    This lecture notes book presents how enhanced structural information of biomolecular ions can be obtained from interaction with photons of specific frequency - laser light. The methods described in the book ""Laser photodissociation and spectroscopy of mass-separated biomolecular ions"" make use of the fact that the discrete energy and fast time scale of photoexcitation can provide more control in ion activation. This activation is the crucial process producing structure-informative product ions that cannot be generated with more conventional heating methods, such as collisional activation. Th

  18. Comparison of structural, thermodynamic, kinetic and mass transport properties of Mg(2+) ion models commonly used in biomolecular simulations.

    Science.gov (United States)

    Panteva, Maria T; Giambaşu, George M; York, Darrin M

    2015-05-15

    The prevalence of Mg(2+) ions in biology and their essential role in nucleic acid structure and function has motivated the development of various Mg(2+) ion models for use in molecular simulations. Currently, the most widely used models in biomolecular simulations represent a nonbonded metal ion as an ion-centered point charge surrounded by a nonelectrostatic pairwise potential that takes into account dispersion interactions and exchange effects that give rise to the ion's excluded volume. One strategy toward developing improved models for biomolecular simulations is to first identify a Mg(2+) model that is consistent with the simulation force fields that closely reproduces a range of properties in aqueous solution, and then, in a second step, balance the ion-water and ion-solute interactions by tuning parameters in a pairwise fashion where necessary. The present work addresses the first step in which we compare 17 different nonbonded single-site Mg(2+) ion models with respect to their ability to simultaneously reproduce structural, thermodynamic, kinetic and mass transport properties in aqueous solution. None of the models based on a 12-6 nonelectrostatic nonbonded potential was able to reproduce the experimental radial distribution function, solvation free energy, exchange barrier and diffusion constant. The models based on a 12-6-4 potential offered improvement, and one model in particular, in conjunction with the SPC/E water model, performed exceptionally well for all properties. The results reported here establish useful benchmark calculations for Mg(2+) ion models that provide insight into the origin of the behavior in aqueous solution, and may aid in the development of next-generation models that target specific binding sites in biomolecules. © 2015 Wiley Periodicals, Inc.

  19. Hybrid Quantum Mechanics/Molecular Mechanics/Coarse Grained Modeling: A Triple-Resolution Approach for Biomolecular Systems.

    Science.gov (United States)

    Sokkar, Pandian; Boulanger, Eliot; Thiel, Walter; Sanchez-Garcia, Elsa

    2015-04-14

    We present a hybrid quantum mechanics/molecular mechanics/coarse-grained (QM/MM/CG) multiresolution approach for solvated biomolecular systems. The chemically important active-site region is treated at the QM level. The biomolecular environment is described by an atomistic MM force field, and the solvent is modeled with the CG Martini force field using standard or polarizable (pol-CG) water. Interactions within the QM, MM, and CG regions, and between the QM and MM regions, are treated in the usual manner, whereas the CG-MM and CG-QM interactions are evaluated using the virtual sites approach. The accuracy and efficiency of our implementation is tested for two enzymes, chorismate mutase (CM) and p-hydroxybenzoate hydroxylase (PHBH). In CM, the QM/MM/CG potential energy scans along the reaction coordinate yield reaction energies that are too large, both for the standard and polarizable Martini CG water models, which can be attributed to adverse effects of using large CG water beads. The inclusion of an atomistic MM water layer (10 Å for uncharged CG water and 5 Å for polarizable CG water) around the QM region improves the energy profiles compared to the reference QM/MM calculations. In analogous QM/MM/CG calculations on PHBH, the use of the pol-CG description for the outer water does not affect the stabilization of the highly charged FADHOOH-pOHB transition state compared to the fully atomistic QM/MM calculations. Detailed performance analysis in a glycine-water model system indicates that computation times for QM energy and gradient evaluations at the density functional level are typically reduced by 40-70% for QM/MM/CG relative to fully atomistic QM/MM calculations.

  20. Scaling analysis of bio-molecular dynamics derived from elastic incoherent neutron scattering experiments

    Energy Technology Data Exchange (ETDEWEB)

    Doster, W. [Physik-Department, Technische Universität München, D-85748 Garching (Germany); Nakagawa, H. [Jülich Centre for Neutron Science, Forschungszentrum Jülich GmbH, Outstation at MLZ, Lichtenbergstraße 1, 85747 Garching (Germany); Japan Atomic Energy Agency, Quantum Beam Science Directorate, Tokai, Ibaraki 319-1195 (Japan); Appavou, M. S. [Jülich Centre for Neutron Science, Forschungszentrum Jülich GmbH, Outstation at MLZ, Lichtenbergstraße 1, 85747 Garching (Germany)

    2013-07-28

    Numerous neutron scattering studies of bio-molecular dynamics employ a qualitative analysis of elastic scattering data and atomic mean square displacements. We provide a new quantitative approach showing that the intensity at zero energy exchange can be a rich source of information of bio-structural fluctuations on a pico- to nano-second time scale. Elastic intensity scans performed either as a function of the temperature (back-scattering) and/or by varying the instrumental resolution (time of flight spectroscopy) yield the activation parameters of molecular motions and the approximate structural correlation function in the time domain. The two methods are unified by a scaling function, which depends on the ratio of correlation time and instrumental resolution time. The elastic scattering concept is illustrated with a dynamic characterization of alanine-dipeptide, protein hydration water, and water-coupled protein motions of lysozyme, per-deuterated c-phycocyanin (CPC) and hydrated myoglobin. The complete elastic scattering function versus temperature, momentum exchange, and instrumental resolution is analyzed instead of focusing on a single cross-over temperature of mean square displacements at the apparent onset temperature of an-harmonic motions. Our method predicts the protein dynamical transition (PDT) at T{sub d} from the collective (α) structural relaxation rates of the solvation shell as input. By contrast, the secondary (β) relaxation enhances the amplitude of fast local motions in the vicinity of the glass temperature T{sub g}. The PDT is specified by step function in the elastic intensity leading from elastic to viscoelastic dynamic behavior at a transition temperature T{sub d}.

  1. Quantum Simulations of Solvated Biomolecules Using Hybrid Methods

    Science.gov (United States)

    Hodak, Miroslav

    2009-03-01

    One of the most important challenges in quantum simulations on biomolecules is efficient and accurate inclusion of the solvent, because the solvent atoms usually outnumber those in the biomolecule of interest. We have developed a hybrid method that allows for explicit quantum-mechanical treatment of the solvent at low computational cost. In this method, Kohn-Sham (KS) density functional theory (DFT) is combined with an orbital-free (OF) DFT. Kohn-Sham (KS) DFT is used to describe the biomolecule and its first solvation shells, while the orbital-free (OF) DFT is employed for the rest of the solvent. The OF part is fully O(N) and capable of handling 10^5 solvent molecules on current parallel supercomputers, while taking only ˜ 10 % of the total time. The compatibility between the KS and OF DFT methods enables seamless integration between the two. In particular, the flow of solvent molecules across the KS/OF interface is allowed and the total energy is conserved. As the first large-scale applications, the hybrid method has been used to investigate the binding of copper ions to proteins involved in prion (PrP) and Parkinson's diseases. Our results for the PrP, which causes mad cow disease when misfolded, resolve a contradiction found in experiments, in which a stronger binding mode is replaced by a weaker one when concentration of copper ions is increased, and show how it can act as a copper buffer. Furthermore, incorporation of copper stabilizes the structure of the full-length PrP, suggesting its protective role in prion diseases. For alpha-synuclein, a Parkinson's disease (PD) protein, we show that Cu binding modifies the protein structurally, making it more susceptible to misfolding -- an initial step in the onset of PD. In collaboration with W. Lu, F. Rose and J. Bernholc.

  2. Symmetrical Parameterization of Rigid Body Transformations for Biomolecular Structures.

    Science.gov (United States)

    Kim, Jin Seob; Chirikjian, Gregory S

    2018-01-01

    Assessing preferred relative rigid body position and orientation is important in the description of biomolecular structures (such as proteins) and their interactions. In this article, we extend and apply the "symmetrical parameterization," which we recently introduced in the kinematics community, to address problems in structural biology. We also review parameterization methods that are widely used in structural biology to describe relative rigid body motions (in particular, orientations) as a basis for comparison. The new symmetrical parameterization is useful in describing the relative biomolecular rigid body motions, where the parameters are symmetrical in the sense that the subunits of a complex biomolecular structure are described in the same way for the corresponding motion and its inverse. The properties of this new parameterization, singularity analysis, and inverse kinematics are also investigated in more detail. Finally, parameterization is applied to real biomolecular structures and a potential application to structure modeling of symmetric macromolecules to show the efficacy of the symmetrical parameterization in the field of computational structural biology.

  3. Transient response characteristics in a biomolecular integral controller.

    Science.gov (United States)

    Sen, Shaunak

    2016-04-01

    The cellular behaviour of perfect adaptation is achieved through the use of an integral control element in the underlying biomolecular circuit. It is generally unclear how integral action affects the important aspect of transient response in these biomolecular systems, especially in light of the fact that it typically deteriorates the transient response in engineering contexts. To address this issue, the authors investigated the transient response in a computational model of a simple biomolecular integral control system involved in bacterial signalling. They find that the transient response can actually speed up as the integral gain parameter increases. On further analysis, they find that the underlying dynamics are composed of slow and fast modes and the speed-up of the transient response is because of the speed-up of the slow-mode dynamics. Finally, they note how an increase in the integral gain parameter also leads to a decrease in the amplitude of the transient response, consistent with the overall improvement in the transient response. These results should be useful in understanding the overall effect of integral action on system dynamics, particularly for biomolecular systems.

  4. Facing and Overcoming Sensitivity Challenges in Biomolecular NMR Spectroscopy

    DEFF Research Database (Denmark)

    Ardenkjær-Larsen, Jan Henrik; Boebinger, Gregory S.; Comment, Arnaud

    2015-01-01

    In the Spring of 2013, NMR spectroscopists convened at the Weizmann Institute in Israel to brainstorm on approaches to improve the sensitivity of NMR experiments, particularly when applied in biomolecular settings. This multi‐author interdisciplinary Review presents a state‐of‐the‐art description...

  5. Quantifying modularity in the evolution of biomolecular systems.

    NARCIS (Netherlands)

    Snel, B.; Huynen, M.A.

    2004-01-01

    Functional modules are considered the primary building blocks of biomolecular systems. Here we study to what extent functional modules behave cohesively across genomes:That is, are functional modules also evolutionary modules? We probe this question by analyzing for a large collection of functional

  6. Biomolecular strategies for cell surface engineering

    Science.gov (United States)

    Wilson, John Tanner

    Islet transplantation has emerged as a promising cell-based therapy for the treatment of diabetes, but its clinical efficacy remains limited by deleterious host responses that underlie islet destruction. In this dissertation, we describe the assembly of ultrathin conformal coatings that confer molecular-level control over the composition and biophysicochemical properties of the islet surface with implications for improving islet engraftment. Significantly, this work provides novel biomolecular strategies for cell surface engineering with broad biomedical and biotechnological applications in cell-based therapeutics and beyond. Encapsulation of cells and tissue offers a rational approach for attenuating deleterious host responses towards transplanted cells, but a need exists to develop cell encapsulation strategies that minimize transplant volume. Towards this end, we endeavored to generate nanothin films of diverse architecture with tunable properties on the extracellular surface of individual pancreatic islets through a process of layer-by-layer (LbL) self assembly. We first describe the formation of poly(ethylene glycol) (PEG)-rich conformal coatings on islets via LbL self assembly of poly(L-lysine)-g-PEG(biotin) and streptavidin. Multilayer thin films conformed to the geometrically and chemically heterogeneous islet surface, and could be assembled without loss of islet viability or function. Significantly, coated islets performed comparably to untreated controls in a murine model of allogenic intraportal islet transplantation, and, to our knowledge, this is the first study to report in vivo survival and function of nanoencapsulated cells or cell aggregates. Based on these findings, we next postulated that structurally similar PLL-g-PEG copolymers comprised of shorter PEG grafts might be used to initiate and propagate the assembly of polyelectrolyte multilayer (PEM) films on pancreatic islets, while simultaneously preserving islet viability. Through control of PLL

  7. A self-regulating biomolecular comparator for processing oscillatory signals.

    Science.gov (United States)

    Agrawal, Deepak K; Franco, Elisa; Schulman, Rebecca

    2015-10-06

    While many cellular processes are driven by biomolecular oscillators, precise control of a downstream on/off process by a biochemical oscillator signal can be difficult: over an oscillator's period, its output signal varies continuously between its amplitude limits and spends a significant fraction of the time at intermediate values between these limits. Further, the oscillator's output is often noisy, with particularly large variations in the amplitude. In electronic systems, an oscillating signal is generally processed by a downstream device such as a comparator that converts a potentially noisy oscillatory input into a square wave output that is predominantly in one of two well-defined on and off states. The comparator's output then controls downstream processes. We describe a method for constructing a synthetic biochemical device that likewise produces a square-wave-type biomolecular output for a variety of oscillatory inputs. The method relies on a separation of time scales between the slow rate of production of an oscillatory signal molecule and the fast rates of intermolecular binding and conformational changes. We show how to control the characteristics of the output by varying the concentrations of the species and the reaction rates. We then use this control to show how our approach could be applied to process different in vitro and in vivo biomolecular oscillators, including the p53-Mdm2 transcriptional oscillator and two types of in vitro transcriptional oscillators. These results demonstrate how modular biomolecular circuits could, in principle, be combined to build complex dynamical systems. The simplicity of our approach also suggests that natural molecular circuits may process some biomolecular oscillator outputs before they are applied downstream. © 2015 The Author(s).

  8. Replica Temperatures for Uniform Exchange and Efficient Roundtrip Times in Explicit Solvent Parallel Tempering Simulations.

    Science.gov (United States)

    Prakash, Meher K; Barducci, Alessandro; Parrinello, Michele

    2011-07-12

    The efficiency of parallel tempering simulations is greatly influenced by the distribution of replica temperatures. In explicit solvent biomolecular simulations, where the total energy is dominated by the solvent, specific heat is usually assumed to be constant. From this, it follows that a geometric distribution of temperatures is optimal. We observe that for commonly used water models (TIP3P, SPC/E) under constant volume conditions and in the range of temperatures normally used, the specific heat is not a constant, consistent with experimental observations. Using this fact, we derive an improved temperature distribution which substantially reduces the round-trip times, especially when working with a small number of replicas.

  9. Redefining solubility parameters: the partial solvation parameters.

    Science.gov (United States)

    Panayiotou, Costas

    2012-03-21

    The present work reconsiders a classical and universally accepted concept of physical chemistry, the solubility parameter. Based on the insight derived from modern quantum chemical calculations, a new definition of solubility parameter is proposed, which overcomes some of the inherent restrictions of the original definition and expands its range of applications. The original single solubility parameter is replaced by four partial solvation parameters reflecting the dispersion, the polar, the acidic and the basic character of the chemical compounds as expressed either in their pure state or in mixtures. Simple rules are adopted for the definition and calculation of these four parameters and their values are tabulated for a variety of common substances. In contrast, however, to the well known Hansen solubility parameters, their design and evaluation does not rely exclusively on the basic rule of "similarity matching" for solubility but it makes also use of the other basic rule of compatibility, namely, the rule of "complementarity matching". This complementarity matching becomes particularly operational with the sound definition of the acidic and basic components of the solvation parameter based on the third σ-moments of the screening charge distributions of the quantum mechanics-based COSMO-RS theory. The new definitions are made in a simple and straightforward manner, thus, preserving the strength and appeal of solubility parameter stemming from its simplicity. The new predictive method has been applied to a variety of solubility data for systems of pharmaceuticals and polymers. The results from quantum mechanics calculations are critically compared with the results from Abraham's acid/base descriptors.

  10. Density functional calculations of {sup 15}N chemical shifts in solvated dipeptides

    Energy Technology Data Exchange (ETDEWEB)

    Cai Ling; Fushman, David, E-mail: fushman@umd.edu; Kosov, Daniel S. [University of Maryland, Department of Chemistry and Biochemistry (United States)], E-mail: dkosov@umd.edu

    2008-06-15

    We performed density functional calculations to examine the effects of solvation, hydrogen bonding, backbone conformation, and the side chain on {sup 15}N chemical shielding in proteins. We used N-methylacetamide (NMA) and N-formyl-alanyl-X (with X being one of the 19 naturally occurring amino acids excluding proline) as model systems. In addition, calculations were performed for selected fragments from protein GB3. The conducting polarizable continuum model was employed to include the effect of solvent in the density functional calculations. Our calculations for NMA show that the augmentation of the polarizable continuum model with the explicit water molecules in the first solvation shell has a significant influence on isotropic {sup 15}N chemical shift but not as much on the chemical shift anisotropy. The difference in the isotropic chemical shift between the standard {beta}-sheet and {alpha}-helical conformations ranges from 0.8 to 6.2 ppm depending on the residue type, with the mean of 2.7 ppm. This is in good agreement with the experimental chemical shifts averaged over a database of 36 proteins containing >6100 amino acid residues. The orientation of the {sup 15}N chemical shielding tensor as well as its anisotropy and asymmetry are also in the range of values experimentally observed for peptides and proteins.

  11. Solvent polarity considerations are unable to describe fullerene solvation behavior.

    Science.gov (United States)

    Chaban, Vitaly V; Maciel, Cleiton; Fileti, Eudes Eterno

    2014-03-27

    Atomistic molecular dynamics simulations were employed to investigate the solvation properties of the fullerene C60 in binary water/dimethyl sulfoxide (DMSO) mixtures. Structural analysis indicates a preferential solvation with the predominance of DMSO molecules in the first solvation shell for the solutions with low concentrations of DMSO. PMF calculations indicate a maximization of the hydrophobic interaction at low concentrations of DMSO. The contact minima indicate a tendency of aggregation of these nanostructures in water/DMSO mixtures and in the both pure solvents. The free energy of solvation suggests that the hydrophobicity of the fullerene increases monotonically with the increase of DMSO concentration. This result is incompatible with the polarity of DMSO, since it was expected that increasing the concentration of DMSO entailed an increase of C60 solubility.

  12. Nonpolar solvation dynamics for a nonpolar solute in room ...

    Indian Academy of Sciences (India)

    Sandipa Indra

    2018-01-30

    7D upon electronic excitation .... of the dipole.62 Nonpolar solvation being dominated by the interaction between the solute and the ...... Trifluoroacetate Ionic Liquid and Its Mixture with Water and Methanol: A Photophysical and ...

  13. Dispersion and Solvation Effects on the Structure and Dynamics of N719 Adsorbed to Anatase Titania (101) Surfaces in Room-Temperature Ionic Liquids: An ab Initio Molecular Simulation Study

    KAUST Repository

    Byrne, Aaron

    2015-12-24

    Ab initio, density functional theory (DFT)-based molecular dynamics (MD) has been carried out to investigate the effect of explicit solvation on the dynamical and structural properties of a [bmim][NTf2] room-temperature ionic liquid (RTIL), solvating a N719 sensitizing dye adsorbed onto an anatase titania (101) surface. The effect of explicit dispersion on the properties of this dye-sensitized solar cell (DSC) interface has also been studied. Upon inclusion of dispersion interactions in simulations of the solvated system, the average separation between the cations and anions decreases by 0.6 Å; the mean distance between the cations and the surface decreases by about 0.5 Å; and the layering of the RTIL is significantly altered in the first layer surrounding the dye, with the cation being on average 1.5 Å further from the center of the dye. Inclusion of dispersion effects when a solvent is not explicitly included (to dampen longer-range interactions) can result in unphysical "kinking" of the adsorbed dye\\'s configuration. The inclusion of solvent shifts the HOMO and LUMO levels of the titania surface by +3 eV. At this interface, the interplay between the effects of dispersion and solvation combines in ways that are often subtle, such as enhancement or inhibition of specific vibrational modes. © 2015 American Chemical Society.

  14. Polymorphism and versatile solvate formation of thiophanate-methyl

    OpenAIRE

    Nauha, Elisa; Saxell, Heidi; Nissinen, Maija; Kolehmainen, Erkki; Schäfer, Ansgar; Schlecker, Rainer

    2009-01-01

    The polymorphism of a fungicide, thiophanate-methyl (TM), was investigated with conventional solvent screening methods. Two polymorphs, the thermodynamically most stable form I and the less stable form II, were found. TM was also found to crystallize as a plethora of different solvates which produced mostly form II upon desolvation. The structures of form I and form II and the fourteen discovered solvates were solved by single crystal X-ray diffraction. The most stable forms were further char...

  15. Estimation of abraham solvation equation coefficients for hydrogen bond formation from abraham solvation parameters for solute activity and basicity

    NARCIS (Netherlands)

    Noort, van P.C.M.

    2013-01-01

    Abraham solvation equations find widespread use in environmental chemistry and pharmaco-chemistry. The coefficients in these equations, which are solvent (system) descriptors, are usually determined by fitting experimental data. To simplify the determination of these coefficients in Abraham

  16. Structure of solvated Fe(CO)5: complex formation during solvation in alcohols.

    Science.gov (United States)

    Lessing, Joshua; Li, Xiaodi; Lee, Taewoo; Rose-Petruck, Christoph G

    2008-03-20

    The equilibrium structure of iron pentacarbonyl, Fe(CO)5, solvated in various alcohols has been investigated by Fourier transform infrared (FTIR) measurements and density functional theory calculations. This system was studied because it is prototypical of a larger class of monometallic systems, which are electronically saturated but not sterically crowded. Upon solvation, the Fe(CO)5 is not just surrounded by a solvation shell. Instead, solute-solvent complexes are formed with the oxygen of the alcohol oriented toward an axial ligand of the Fe(CO)5 giving a formation energy on the order of -5 kJ/mol. This complexation is not a chemical reaction but rather a "preassembly" of the solute molecules with a single solvent molecule. For instance, at room temperature the interaction between Fe(CO)5 and ethanol results in 87% of all Fe(CO)5 molecules being complexated with a single ethanol molecule. This complexation was found in all the alcohol systems studied in this paper. The stability of these complexes was found to depend on the alcohol chain length and branching. The observed complexation mechanism is accompanied by an electron density shift from the complexed alcohol molecule toward Fe(CO)5 where it induces a dipole moment. The finding that Fe(CO)5 forms a complex with the hydroxyl group of a single solvent molecule might have significant implications for ligand substitution reactions. This implies that ligand substitution reactions do not have to proceed via a dissociative mechanism. Instead, the reaction might proceed through a concerted mechanism with the leaving CO simultaneously being replaced by the incoming alcohol that was complexed to Fe(CO)5 prior to the photoexcitation.

  17. Water-enhanced solvation of organics

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jane H. [Univ. of California, Berkeley, CA (United States)

    1993-07-01

    Water-enhanced solvation (WES) was explored for Lewis acid solutes in Lewis base organic solvents, to develop cheap extract regeneration processes. WES for solid solutes was determined from ratios of solubilities of solutes in water-sat. and low-water solvent; both were determined from solid-liquid equilibrium. Vapor-headspace analysis was used to determine solute activity coefficients as function of organic phase water concentration. WES magnitudes of volatile solutes were normalized, set equal to slope of log γs vs xw/xs curve. From graph shape Δ(log γs) represents relative change in solute activity coefficient. Solutes investigated by vapor-headspace analysis were acetic acid, propionic acid, ethanol, 1,2-propylene glycol, 2,3-butylene glycol. Monocarboxylic acids had largest decrease in activity coefficient with water addition followed by glycols and alcohols. Propionic acid in cyclohexanone showed greatest water-enhancement Δ(log γacid)/Δ(xw/xacid) = -0.25. In methylcyclohexanone, the decrease of the activity coefficient of propionic acid was -0.19. Activity coefficient of propionic acid in methylcyclohexanone stopped decreasing once the water reached a 2:1 water to acid mole ratio, implying a stoichiometric relation between water, ketone, and acid. Except for 2,3-butanediol, activity coefficients of the solutes studied decreased monotonically with water content. Activity coefficient curves of ethanol, 1,2-propanediol and 2,3-butanediol did not level off at large water/solute mole ratio. Solutes investigated by solid-liquid equilibrium were citric acid, gallic acid, phenol, xylenols, 2-naphthol. Saturation concentration of citric acid in anhydrous butyl acetate increased from 0.0009 to 0.087 mol/L after 1.3 % (g/g) water co-dissolved into organic phase. Effect of water-enhanced solvation for citric acid is very large but very small for phenol and its derivatives.

  18. Computational studies on intermolecular interactions in solvation

    Science.gov (United States)

    Song, Weiping

    This thesis presents the results of computational studies of intermolecular interactions in various contexts. We first investigated the relation between solute-solvent intermolecular interactions and local density augmentation in supercritical solvation. The phenomenon of interest is the excess density that exists in the neighborhood of an attractive solute in a supercritical solvent in the vicinity of the critical point. In Chapter 2, we examined the ability of various measures of the strength of solute-solvent interactions, calculated from all-atom potential functions, to correlate the extent of local density augmentation in both experimental and model solvents. The Gibbs Ensemble Monte Carlo (GEMC) method enables us to calculate phase equilibrium in pure substances and mixtures. It provides a convenient way to test and develop model potentials. In Chapter 3 we present some methodological aspects of such calculations, the issues related to approach to critical points and finite-size effects and applications to simple fluids. Chapter 4 then describes a simplified 2-site potential model for simulating supercritical fluoroform. The GEMC method was used to simulate the vapor-liquid coexistence curve of the model fluid and the dynamic properties were studied by performing NVT molecular dynamics (MD) simulations. The results show that despite its simplicity, this model is able to reproduce many important properties of supercritical fluoroform, making it useful in molecular simulations of supercritical solvation. In the above two studies, the intermolecular interactions are described by a sum of pair-wise additive Lennard-Jones + Coulomb terms. The standard Lorentz-Berthelot combining rules (geometric mean rule for well depth and arithmetic mean rule for collision diameter) are commonly applied to account for the unlike pair Lennard-Jones parameters. In Chapter 5, we examined the applicability of the combining rules for modeling alkane-perfluoroalkane interactions. It

  19. Inferring biomolecular interaction networks based on convex optimization.

    Science.gov (United States)

    Han, Soohee; Yoon, Yeoin; Cho, Kwang-Hyun

    2007-10-01

    We present an optimization-based inference scheme to unravel the functional interaction structure of biomolecular components within a cell. The regulatory network of a cell is inferred from the data obtained by perturbation of adjustable parameters or initial concentrations of specific components. It turns out that the identification procedure leads to a convex optimization problem with regularization as we have to achieve the sparsity of a network and also reflect any a priori information on the network structure. Since the convex optimization has been well studied for a long time, a variety of efficient algorithms were developed and many numerical solvers are freely available. In order to estimate time derivatives from discrete-time samples, a cubic spline fitting is incorporated into the proposed optimization procedure. Throughout simulation studies on several examples, it is shown that the proposed convex optimization scheme can effectively uncover the functional interaction structure of a biomolecular regulatory network with reasonable accuracy.

  20. Physics at the biomolecular interface fundamentals for molecular targeted therapy

    CERN Document Server

    Fernández, Ariel

    2016-01-01

    This book focuses primarily on the role of interfacial forces in understanding biological phenomena at the molecular scale. By providing a suitable statistical mechanical apparatus to handle the biomolecular interface, the book becomes uniquely positioned to address core problems in molecular biophysics. It highlights the importance of interfacial tension in delineating a solution to the protein folding problem, in unravelling the physico-chemical basis of enzyme catalysis and protein associations, and in rationally designing molecular targeted therapies. Thus grounded in fundamental science, the book develops a powerful technological platform for drug discovery, while it is set to inspire scientists at any level in their careers determined to address the major challenges in molecular biophysics. The acknowledgment of how exquisitely the structure and dynamics of proteins and their aqueous environment are related attests to the overdue recognition that biomolecular phenomena cannot be effectively understood w...

  1. An Assembly Funnel Makes Biomolecular Complex Assembly Efficient

    Science.gov (United States)

    Zenk, John; Schulman, Rebecca

    2014-01-01

    Like protein folding and crystallization, the self-assembly of complexes is a fundamental form of biomolecular organization. While the number of methods for creating synthetic complexes is growing rapidly, most require empirical tuning of assembly conditions and/or produce low yields. We use coarse-grained simulations of the assembly kinetics of complexes to identify generic limitations on yields that arise because of the many simultaneous interactions allowed between the components and intermediates of a complex. Efficient assembly occurs when nucleation is fast and growth pathways are few, i.e. when there is an assembly “funnel”. For typical complexes, an assembly funnel occurs in a narrow window of conditions whose location is highly complex specific. However, by redesigning the components this window can be drastically broadened, so that complexes can form quickly across many conditions. The generality of this approach suggests assembly funnel design as a foundational strategy for robust biomolecular complex synthesis. PMID:25360818

  2. Ultrafast solvation dynamics at internal site of staphylococcal nuclease investigated by site-directed mutagenesis

    CERN Document Server

    Guang-yu, Gao; Wei, Wang; Shu-feng, Wang; Zhong, Dongping; Qi-huang, Gong

    2014-01-01

    Solvation is essential for protein activities. To study internal solvation of protein, site-directed mutagenesis is applied. Intrinsic fluorescent probe, tryptophan, is inserted into desired position inside protein molecule for ultrafast spectroscopic study. Here we review this unique method for protein dynamics researches. We introduce the frontiers of protein solvation, site-directed mutagenesis, protein stability and characteristics, and the spectroscopic methods. Then we present time-resolved spectroscopic dynamics of solvation dynamics inside caves of active sites. The studies are carried out on a globular protein, staphylococcal nuclease. The solvation at internal sites of the caves indicate clear characteristics of local environment. These solvation behaviors correlated to the enzyme activity directly.

  3. Bond Graph Modeling of Chemiosmotic Biomolecular Energy Transduction.

    Science.gov (United States)

    Gawthrop, Peter J

    2017-04-01

    Engineering systems modeling and analysis based on the bond graph approach has been applied to biomolecular systems. In this context, the notion of a Faraday-equivalent chemical potential is introduced which allows chemical potential to be expressed in an analogous manner to electrical volts thus allowing engineering intuition to be applied to biomolecular systems. Redox reactions, and their representation by half-reactions, are key components of biological systems which involve both electrical and chemical domains. A bond graph interpretation of redox reactions is given which combines bond graphs with the Faraday-equivalent chemical potential. This approach is particularly relevant when the biomolecular system implements chemoelectrical transduction - for example chemiosmosis within the key metabolic pathway of mitochondria: oxidative phosphorylation. An alternative way of implementing computational modularity using bond graphs is introduced and used to give a physically based model of the mitochondrial electron transport chain To illustrate the overall approach, this model is analyzed using the Faraday-equivalent chemical potential approach and engineering intuition is used to guide affinity equalisation: a energy based analysis of the mitochondrial electron transport chain.

  4. Modular bond-graph modelling and analysis of biomolecular systems.

    Science.gov (United States)

    Gawthrop, Peter J; Crampin, Edmund J

    2016-10-01

    Bond graphs can be used to build thermodynamically-compliant hierarchical models of biomolecular systems. As bond graphs have been widely used to model, analyse and synthesise engineering systems, this study suggests that they can play the same rôle in the modelling, analysis and synthesis of biomolecular systems. The particular structure of bond graphs arising from biomolecular systems is established and used to elucidate the relation between thermodynamically closed and open systems. Block diagram representations of the dynamics implied by these bond graphs are used to reveal implicit feedback structures and are linearised to allow the application of control-theoretical methods. Two concepts of modularity are examined: computational modularity where physical correctness is retained and behavioural modularity where module behaviour (such as ultrasensitivity) is retained. As well as providing computational modularity, bond graphs provide a natural formulation of behavioural modularity and reveal the sources of retroactivity. A bond graph approach to reducing retroactivity, and thus inter-module interaction, is shown to require a power supply such as that provided by the ATP ⇌ ADP + Pi reaction. The mitogen-activated protein kinase cascade (Raf-MEK-ERK pathway) is used as an illustrative example.

  5. Biomolecular templating of functional hybrid nanostructures using repeat protein scaffolds.

    Science.gov (United States)

    Romera, David; Couleaud, Pierre; Mejias, Sara H; Aires, Antonio; Cortajarena, Aitziber L

    2015-10-01

    The precise synthesis of materials and devices with tailored complex structures and properties is a requisite for the development of the next generation of products based on nanotechnology. Nowadays, the technology for the generation of this type of devices lacks the precision to determine their properties and is accomplished mostly by 'trial and error' experimental approaches. The use of bottom-up approaches that rely on highly specific biomolecular interactions of small and simple components is an attractive approach for the templating of nanoscale elements. In nature, protein assemblies define complex structures and functions. Engineering novel bio-inspired assemblies by exploiting the same rules and interactions that encode the natural diversity is an emerging field that opens the door to create nanostructures with numerous potential applications in synthetic biology and nanotechnology. Self-assembly of biological molecules into defined functional structures has a tremendous potential in nano-patterning and the design of novel materials and functional devices. Molecular self-assembly is a process by which complex 3D structures with specified functions are constructed from simple molecular building blocks. Here we discuss the basis of biomolecular templating, the great potential of repeat proteins as building blocks for biomolecular templating and nano-patterning. In particular, we focus on the designed consensus tetratricopeptide repeats (CTPRs), the control on the assembly of these proteins into higher order structures and their potential as building blocks in order to generate functional nanostructures and materials. © 2015 Authors; published by Portland Press Limited.

  6. Retroactivity in the Context of Modularly Structured Biomolecular Systems.

    Science.gov (United States)

    Pantoja-Hernández, Libertad; Martínez-García, Juan Carlos

    2015-01-01

    Synthetic biology has intensively promoted the technical implementation of modular strategies in the fabrication of biological devices. Modules are considered as networks of reactions. The behavior displayed by biomolecular systems results from the information processes carried out by the interconnection of the involved modules. However, in natural systems, module wiring is not a free-of-charge process; as a consequence of interconnection, a reactive phenomenon called retroactivity emerges. This phenomenon is characterized by signals that propagate from downstream modules (the modules that receive the incoming signals upon interconnection) to upstream ones (the modules that send the signals upon interconnection). Such retroactivity signals, depending of their strength, may change and sometimes even disrupt the behavior of modular biomolecular systems. Thus, analysis of retroactivity effects in natural biological and biosynthetic systems is crucial to achieve a deeper understanding of how this interconnection between functionally characterized modules takes place and how it impacts the overall behavior of the involved cell. By discussing the modules interconnection in natural and synthetic biomolecular systems, we propose that such systems should be considered as quasi-modular.

  7. Solvation of polymers as mutual association. I. General theory

    Science.gov (United States)

    Dudowicz, Jacek; Freed, Karl F.; Douglas, Jack F.

    2013-04-01

    A Flory-Huggins (FH) type lattice theory of self-assembly is generalized to describe the equilibrium solvation of long polymer chains B by small solvent molecules A. Solvation is modeled as a thermally reversible mutual association between the polymer and a relatively low molar mass solvent. The FH Helmholtz free energy F is derived for a mixture composed of the A and B species and the various possible mutual association complexes AiB, and F is then used to generate expressions for basic thermodynamic properties of solvated polymer solutions, including the size distribution of the solvated clusters, the fraction of solvent molecules contained in solvated states (an order parameter for solvation), the specific heat (which exhibits a maximum at the solvation transition), the second and the third osmotic virial coefficients, and the boundaries for phase stability of the mixture. Special attention is devoted to the analysis of the "entropic" contribution χs to the FH interaction parameter χ of polymer solutions, both with and without associative interactions. The entropic χs parameter arises from correlations associated with polymer chain connectivity and disparities in molecular structure between the components of the mixture. Our analysis provides the first explanation of the longstanding enigma of why χs for polymer solutions significantly exceeds χs for binary polymer blends. Our calculations also reveal that χs becomes temperature dependent when interactions are strong, in sharp contrast to models currently being used for fitting thermodynamic data of associating polymer-solvent mixtures, where χs is simply assumed to be an adjustable constant based on experience with solutions of homopolymers in nonassociating solvents.

  8. Biomolecular Programming of Discrete Nanomaterials for Sensors, Templates and Mimics of Natural Nanoscale Assemblies

    Science.gov (United States)

    2016-10-17

    AFRL-AFOSR-VA-TR-2016-0343 BIOMOLECULAR PROGRAMMING OF DISCRETE NANOMATERIALS FOR SENSORS, TEMPLATES AND MIMICS OF NATURAL NANOSCALE ASSEMBLIES...Performance 3. DATES COVERED (From - To) 01 Jun 2011 to 31 May 2016 4. TITLE AND SUBTITLE BIOMOLECULAR PROGRAMMING OF DISCRETE NANOMATERIALS FOR SENSORS...term use are needed; hence our interest in stabilized but responsive biomolecular materials and conjugates between 2011 and 2016. In terms of melanin

  9. Stealth effect of biomolecular corona on nanoparticle uptake by immune cells.

    Science.gov (United States)

    Caracciolo, Giulio; Palchetti, Sara; Colapicchioni, Valentina; Digiacomo, Luca; Pozzi, Daniela; Capriotti, Anna Laura; La Barbera, Giorgia; Laganà, Aldo

    2015-10-06

    When injected in a biological milieu, a nanomaterial rapidly adsorbs biomolecules forming a biomolecular corona. The biomolecular corona changes the interfacial composition of a nanomaterial giving it a biological identity that determines the physiological response. Characterization of the biomolecular structure and composition has received increasing attention mostly due to its detrimental impact on the nanomaterial's metabolism in vivo. It is generally accepted that an opsonin-enriched biomolecular corona promotes immune system recognition and rapid clearance from circulation. Here we applied dynamic light scattering and nanoliquid chromatography tandem mass spectrometry to thoroughly characterize the biomolecular corona formed around lipid and silica nanoparticles (NPs). Incubation with human plasma resulted in the formation of NP-biomolecular coronas enriched with immunoglobulins, complement factors, and coagulation proteins that bind to surface receptors on immune cells and elicit phagocytosis. Conversely, we found that protein-coated NPs were protected from uptake by macrophage RAW 264.7 cells. This implies that the biomolecular corona formation provides a stealth effect on macrophage recognition. Our results suggest that correct prediction of the NP's fate in vivo will require more than just the knowledge of the biomolecular corona composition. Validation of efficient methods for mapping protein binding sites on the biomolecular corona of NPs is an urgent task for future research.

  10. Lithium solvation in dimethyl sulfoxide-acetonitrile mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Semino, Rocío; Zaldívar, Gervasio; Calvo, Ernesto J. [Departamento de Química Inorgánica Analítica y Química-Física e INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, 1428 Buenos Aires (Argentina); Laria, Daniel, E-mail: dhlaria@cnea.gov.ar [Departamento de Química Inorgánica Analítica y Química-Física e INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, 1428 Buenos Aires (Argentina); Departamento de Física de la Materia Condensada, Comisión Nacional de Energía Atómica, Avenida Libertador 8250, 1429 Buenos Aires (Argentina)

    2014-12-07

    We present molecular dynamics simulation results pertaining to the solvation of Li{sup +} in dimethyl sulfoxide-acetonitrile binary mixtures. The results are potentially relevant in the design of Li-air batteries that rely on aprotic mixtures as solvent media. To analyze effects derived from differences in ionic size and charge sign, the solvation of Li{sup +} is compared to the ones observed for infinitely diluted K{sup +} and Cl{sup −} species, in similar solutions. At all compositions, the cations are preferentially solvated by dimethyl sulfoxide. Contrasting, the first solvation shell of Cl{sup −} shows a gradual modification in its composition, which varies linearly with the global concentrations of the two solvents in the mixtures. Moreover, the energetics of the solvation, described in terms of the corresponding solute-solvent coupling, presents a clear non-ideal concentration dependence. Similar nonlinear trends were found for the stabilization of different ionic species in solution, compared to the ones exhibited by their electrically neutral counterparts. These tendencies account for the characteristics of the free energy associated to the stabilization of Li{sup +}Cl{sup −}, contact-ion-pairs in these solutions. Ionic transport is also analyzed. Dynamical results show concentration trends similar to those recently obtained from direct experimental measurements.

  11. The solvation of electrons by an atmospheric-pressure plasma

    Science.gov (United States)

    Rumbach, Paul; Bartels, David M.; Sankaran, R. Mohan; Go, David B.

    2015-01-01

    Solvated electrons are typically generated by radiolysis or photoionization of solutes. While plasmas containing free electrons have been brought into contact with liquids in studies dating back centuries, there has been little evidence that electrons are solvated by this approach. Here we report direct measurements of solvated electrons generated by an atmospheric-pressure plasma in contact with the surface of an aqueous solution. The electrons are measured by their optical absorbance using a total internal reflection geometry. The measured absorption spectrum is unexpectedly blue shifted, which is potentially due to the intense electric field in the interfacial Debye layer. We estimate an average penetration depth of 2.5±1.0 nm, indicating that the electrons fully solvate before reacting through second-order recombination. Reactions with various electron scavengers including H+, NO2−, NO3− and H2O2 show that the kinetics are similar, but not identical, to those for solvated electrons formed in bulk water by radiolysis. PMID:26088017

  12. An expanded framework for biomolecular visualization in the classroom: Learning goals and competencies.

    Science.gov (United States)

    Dries, Daniel R; Dean, Diane M; Listenberger, Laura L; Novak, Walter R P; Franzen, Margaret A; Craig, Paul A

    2017-01-02

    A thorough understanding of the molecular biosciences requires the ability to visualize and manipulate molecules in order to interpret results or to generate hypotheses. While many instructors in biochemistry and molecular biology use visual representations, few indicate that they explicitly teach visual literacy. One reason is the need for a list of core content and competencies to guide a more deliberate instruction in visual literacy. We offer here the second stage in the development of one such resource for biomolecular three-dimensional visual literacy. We present this work with the goal of building a community for online resource development and use. In the first stage, overarching themes were identified and submitted to the biosciences community for comment: atomic geometry; alternate renderings; construction/annotation; het group recognition; molecular dynamics; molecular interactions; monomer recognition; symmetry/asymmetry recognition; structure-function relationships; structural model skepticism; and topology and connectivity. Herein, the overarching themes have been expanded to include a 12th theme (macromolecular assemblies), 27 learning goals, and more than 200 corresponding objectives, many of which cut across multiple overarching themes. The learning goals and objectives offered here provide educators with a framework on which to map the use of molecular visualization in their classrooms. In addition, the framework may also be used by biochemistry and molecular biology educators to identify gaps in coverage and drive the creation of new activities to improve visual literacy. This work represents the first attempt, to our knowledge, to catalog a comprehensive list of explicit learning goals and objectives in visual literacy. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):69-75, 2017. © 2016 The Authors Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union

  13. Computational Prediction of Solvation Free Energies of Amino Acids with Genetic Algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jung Hum; Park, Hwang Seo [Sejong University, Seoul (Korea, Republic of); Lee, Jin Won [Hanyang University, Seoul (Korea, Republic of)

    2010-05-15

    We propose an improved solvent contact model to estimate the solvation free energies of amino acids from individual atomic contributions. The modification of the solvation model involves the optimization of three kinds of parameters in the solvation free energy function: atomic fragmental volume, maximum atomic occupancy, and atomic solvation parameters. All of these atomic parameters for 17 atom types are developed by the operation of a standard genetic algorithm in such a way to minimize the difference between experimental and calculated solvation free energies. The present solvation model is able to predict the experimental solvation free energies of amino acids with the squared correlation coefficients of 0.94 and 0.93 for the parameterization with Gaussian and screened Coulomb potential as the envelope functions, respectively. This result indicates that the improved solvent contact model with the newly developed atomic parameters would be a useful tool for the estimation of the molecular solvation free energy of a protein in aqueous solution.

  14. Novel analysis of cation solvation using a graph theoretic approach.

    Science.gov (United States)

    Mooney, Barbara Logan; Corrales, L Rene; Clark, Aurora E

    2012-04-12

    A new method for analyzing molecular dynamics simulation data is employed to study the solvent shell structure and exchange processes of mono-, di-, and trivalent metal cations in water. The instantaneous coordination environment is characterized in terms of the coordinating waters' H-bonding network, orientations, mean residence times, and the polyhedral configuration. The graph-theory-based algorithm provides a rapid frame-by-frame identification of polyhedra and reveals fluctuations in the solvation shell shape--previously unexplored dynamic behavior that in many cases can be associated with the exchange reactions of water between the first and second solvation shells. Extended solvation structure is also analyzed graphically, revealing details of the hydrogen bonding network that have practical implications for connecting molecular dynamics data to ab initio cluster calculations. Although the individual analyses of water orientation, residence time, etc., are commonplace in the literature, their combination with graphical algorithms is new and provides added chemical insight.

  15. Prediction of solvation enthalpy of gaseous organic compounds in propanol

    Science.gov (United States)

    Golmohammadi, Hassan; Dashtbozorgi, Zahra

    2016-09-01

    The purpose of this paper is to present a novel way for developing quantitative structure-property relationship (QSPR) models to predict the gas-to-propanol solvation enthalpy (Δ H solv) of 95 organic compounds. Different kinds of descriptors were calculated for each compound using the Dragon software package. The variable selection technique of replacement method (RM) was employed to select the optimal subset of solute descriptors. Our investigation reveals that the dependence of physical chemistry properties of solution on solvation enthalpy is nonlinear and that the RM method is unable to model the solvation enthalpy accurately. The results established that the calculated Δ H solv values by SVM were in good agreement with the experimental ones, and the performances of the SVM models were superior to those obtained by RM model.

  16. SISGR: Linking Ion Solvation and Lithium Battery Electrolyte Properties

    Energy Technology Data Exchange (ETDEWEB)

    Trulove, Paul C. [U.S. Naval Academy, Annapolis, MD (United States); Foley, Matthew P. [U.S. Naval Academy, Annapolis, MD (United States)

    2012-09-30

    The solvation and phase behavior of the model battery electrolyte salt lithium trifluoromethanesulfonate (LiCF3SO3) in commonly used organic solvents; ethylene carbonate (EC), gamma-butyrolactone (GBL), and propylene carbonate (PC) was explored. Data from differential scanning calorimetry (DSC), Raman spectroscopy, and X-ray diffraction were correlated to provide insight into the solvation states present within a sample mixture. Data from DSC analyses allowed the construction of phase diagrams for each solvent system. Raman spectroscopy enabled the determination of specific solvation states present within a solvent-salt mixture, and X-ray diffraction data provided exact information concerning the structure of a solvates that could be isolated Thermal analysis of the various solvent-salt mixtures revealed the phase behavior of the model electrolytes was strongly dependent on solvent symmetry. The point groups of the solvents were (in order from high to low symmetry): C2V for EC, CS for GBL, and C1 for PC(R). The low symmetry solvents exhibited a crystallinity gap that increased as solvent symmetry decreased; no gap was observed for EC-LiTf, while a crystallinity gap was observed spanning 0.15 to 0.3 mole fraction for GBL-LiTf, and 0.1 to 0.33 mole fraction for PC(R)-LiTf mixtures. Raman analysis demonstrated the dominance of aggregated species in almost all solvent compositions. The AGG and CIP solvates represent the majority of the species in solutions for the more concentrated mixtures, and only in very dilute compositions does the SSIP solvate exist in significant amounts. Thus, the poor charge transport characteristics of CIP and AGG account for the low conductivity and transport properties of LiTf and explain why is a poor choice as a source of Li+ ions in a Li-ion battery.

  17. Water Evaporation and Conformational Changes from Partially Solvated Ubiquitin

    Directory of Open Access Journals (Sweden)

    Saravana Prakash Thirumuruganandham

    2010-01-01

    Full Text Available Using molecular dynamics simulation, we study the evaporation of water molecules off partially solvated ubiquitin. The evaporation and cooling rates are determined for a molecule at the initial temperature of 300 K. The cooling rate is found to be around 3 K/ns, and decreases with water temperature in the course of the evaporation. The conformation changes are monitored by studying a variety of intermediate partially solvated ubiquitin structures. We find that ubiquitin shrinks with decreasing hydration shell and exposes more of its hydrophilic surface area to the surrounding.

  18. Studies of cosolvent systems in supercritical ethane using solvated electrons.

    Energy Technology Data Exchange (ETDEWEB)

    Dimitrijevic, N. M.; Bartels, D. M.; Jonah, C. D.; Takahashi, K.

    2000-11-14

    In this paper, pulse-radiolytic studies of the methanol-ethane cosolvent system are carried out. Our results show that at temperatures below approximately 110 C, there are high local concentrations of alcohols (clusters) that are capable of solvating an electron, suggesting a size of approximately 4-5 methanol molecules at approximately 0.15 mole fraction alcohol. Reactions have been carried out between these solvated electrons and silver ions that are (presumably) dissolved in other small clusters of alcohols. These results show that the reaction between species in two different clusters is approximately 2 orders of magnitude slower than diffusion-controlled reactions.

  19. Benchmarking a Fast Proton Titration Scheme in Implicit Solvent for Biomolecular Simulations.

    Science.gov (United States)

    Barroso da Silva, Fernando Luís; MacKernan, Donal

    2017-06-13

    pH is a key parameter for technological and biological processes, intimately related to biomolecular charge. As such, it controls biomolecular conformation and intermolecular interactions, for example, protein/RNA stability and folding, enzyme activity, regulation through conformational switches, protein-polyelectrolyte association, and protein-RNA interactions. pH also plays an important role in technological systems in food, brewing, pharma, bioseparations, and biomaterials in general. Predicting the structure of large proteins and complexes remains a great challenge experimentally, industrially, and theoretically, despite the variety of numerical schemes available ranging from Poisson-Boltzmann approaches to explicit solvent based methods. In this work we benchmark a fast proton titration scheme against experiment and several theoretical methods on the following set of representative proteins: [HP36, BBL, HEWL (triclinic and orthorhombic), RNase, SNASE (V66K/WT, V66K/PHS, V66K/Δ+PHS, L38D/Δ+PHS, L38E/Δ+PHS, L38K/Δ+PHS), ALAC, and OMTKY3]; routinely used in similar tests due to the diversity of their structural features. Our scheme is rooted in the classical Tanford-Kirkwood model of impenetrable spheres, where salt is treated at the Debye-Hückel level. Treating salt implicitly dramatically reduces the computation time, thereby circumventing sampling difficulties faced by other numerical schemes. In comparison with experimental measurements, our calculated pKa values have the average, maximum absolute, and root-mean-square deviations of 0.4-0.9, 1.0-5.2, and 0.5-1.2 pH units, respectively. These values are within the ranges commonly observed in theoretical models. They are also in the large majority of the cases studied here more accurate than the NULL model. For BBL, ALAC, and OMTKY3, the predicted pKa are closer to experimental results than other analyzed theoretical data. Despite the intrinsic approximations of the fast titration scheme, its robustness

  20. Shared solvation of sodium ions in alcohol-water solutions explains the non-ideality of free energy of solvation.

    Science.gov (United States)

    Lange, Kathrin M; Bergmann, Ulf; Hodeck, Kai F; Könnecke, René; Schade, Ulrich; Aziz, Emad F

    2011-09-14

    In order to explain the discrepancies between theories and experiments regarding the non-ideality in the free energy of solvation, here we present a microscopic picture of sodium ions dissolved in water-alcohol mixed solvents. We used X-ray absorption spectroscopy to probe the K-edge of sodium ions in mixed solvents of water and alcohols (methanol, ethanol) and in the respective pure solvents. In the mixed solvents a shared solvation of the sodium ions is observed. We find that specifically the water component plays a key role in stabilizing the solvation shell in mixed solvents, which was revealed by a selective photochemical process occurring only in the pure alcohol solvents. This journal is © the Owner Societies 2011

  1. GPU-Accelerated Exploration of Biomolecular Energy Landscapes.

    Science.gov (United States)

    Mantell, Rosemary G; Pitt, Catherine E; Wales, David J

    2016-12-13

    We present graphics processing unit (GPU)-acceleration of various computational energy landscape methods for biomolecular systems. Basin-hopping global optimization, the doubly nudged elastic band method (DNEB), hybrid eigenvector-following (EF), and a local rigid body framework are described, including details of GPU implementations. We analyze the results for eight different system sizes, and consider the effects of history size for minimization and local rigidification on the overall efficiency. We demonstrate improvement relative to CPU performance of up to 2 orders of magnitude for the largest systems.

  2. Building an explicit de Sitter

    Energy Technology Data Exchange (ETDEWEB)

    Louis, Jan [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Hamburg Univ. (Germany). Zentrum fuer Mathematische Physik; Rummel, Markus; Valandro, Roberto [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Westphal, Alexander [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Gruppe Theorie

    2012-11-15

    We construct an explicit example of a de Sitter vacuum in type IIB string theory that realizes the proposal of Kaehler uplifting. As the large volume limit in this method depends on the rank of the largest condensing gauge group we carry out a scan of gauge group ranks over the Kreuzer-Skarke set of toric Calabi-Yau threefolds. We find large numbers of models with the largest gauge group factor easily exceeding a rank of one hundred. We construct a global model with Kaehler uplifting on a two-parameter model on CP{sup 4}{sub 11169}, by an explicit analysis from both the type IIB and F-theory point of view. The explicitness of the construction lies in the realization of a D7 brane configuration, gauge flux and RR and NS flux choices, such that all known consistency conditions are met and the geometric moduli are stabilized in a metastable de Sitter vacuum with spontaneous GUT scale supersymmetry breaking driven by an F-term of the Kaehler moduli.

  3. Creating biomolecular motors based on dynein and actin-binding proteins.

    Science.gov (United States)

    Furuta, Akane; Amino, Misako; Yoshio, Maki; Oiwa, Kazuhiro; Kojima, Hiroaki; Furuta, Ken'ya

    2017-03-01

    Biomolecular motors such as myosin, kinesin and dynein are protein machines that can drive directional movement along cytoskeletal tracks and have the potential to be used as molecule-sized actuators. Although control of the velocity and directionality of biomolecular motors has been achieved, the design and construction of novel biomolecular motors remains a challenge. Here we show that naturally occurring protein building blocks from different cytoskeletal systems can be combined to create a new series of biomolecular motors. We show that the hybrid motors-combinations of a motor core derived from the microtubule-based dynein motor and non-motor actin-binding proteins-robustly drive the sliding movement of an actin filament. Furthermore, the direction of actin movement can be reversed by simply changing the geometric arrangement of these building blocks. Our synthetic strategy provides an approach to fabricating biomolecular machines that work along artificial tracks at nanoscale dimensions.

  4. Effect of C60 adducts on the dynamic structure of aromatic solvation shells

    Science.gov (United States)

    Peerless, James S.; Bowers, G. Hunter; Kwansa, Albert L.; Yingling, Yaroslava G.

    2017-06-01

    We report herein on the use of all-atom molecular dynamics simulations to investigate the solvation environment of C60 and four C60-derived fullerenes immersed in a variety of aromatic solvents. Utilizing a recently developed solvation shell analysis technique that quantifies the spatial relationships between fullerenes and solvent on a molecular level, we show that the number of fullerene substituents and solvent chemistry are crucial determinants of the solvation shell structure and thus fullerene solvation behavior. Specifically, it is shown for the derivatives investigated that the number of fullerene substituents is more critical to solvation behavior than the substituent chemistry.

  5. Biomolecular interaction analysis for carbon nanotubes and for biocompatibility prediction.

    Science.gov (United States)

    Chen, Xiaoping; Fang, Jinzhang; Cheng, Yun; Zheng, Jianhui; Zhang, Jingjing; Chen, Tao; Ruan, Benfang Helen

    2016-07-15

    The interactions between carbon nanotubes (CNTs) and biologics have been commonly studied by various microscopy and spectroscopy methods. We tried biomolecular interaction analysis to measure the kinetic interactions between proteins and CNTs. The analysis demonstrated that wheat germ agglutinin (WGA) and other proteins have high affinity toward carboxylated CNT (f-MWCNT) but essentially no binding to normal CNT (p-MWCNT). The binding of f-MWCNT-protein showed dose dependence, and the observed kinetic constants were in the range of 10(-9) to 10(-11) M with very small off-rates (10(-3) to 10(-7) s(-1)), indicating a relatively tight and stable f-MWCNT-protein complex formation. Interestingly in hemolysis assay, p-MWCNT showed good biocompatibility, f-MWCNT caused 30% hemolysis, but WGA-coated f-MWCNT did not show hemolysis. Furthermore, the f-MWCNT-WGA complex demonstrated enhanced cytotoxicity toward cancer cells, perhaps through the glycoproteins expressed on the cells' surface. Taken together, biomolecular interaction analysis is a precise method that might be useful in evaluating the binding affinity of biologics to CNTs and in predicting biological actions. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations.

    Science.gov (United States)

    Vergara-Perez, Sandra; Marucho, Marcelo

    2016-01-01

    One of the most used and efficient approaches to compute electrostatic properties of biological systems is to numerically solve the Poisson-Boltzmann (PB) equation. There are several software packages available that solve the PB equation for molecules in aqueous electrolyte solutions. Most of these software packages are useful for scientists with specialized training and expertise in computational biophysics. However, the user is usually required to manually take several important choices, depending on the complexity of the biological system, to successfully obtain the numerical solution of the PB equation. This may become an obstacle for researchers, experimentalists, even students with no special training in computational methodologies. Aiming to overcome this limitation, in this article we present MPBEC, a free, cross-platform, open-source software that provides non-experts in the field an easy and efficient way to perform biomolecular electrostatic calculations on single processor computers. MPBEC is a Matlab script based on the Adaptative Poisson Boltzmann Solver, one of the most popular approaches used to solve the PB equation. MPBEC does not require any user programming, text editing or extensive statistical skills, and comes with detailed user-guide documentation. As a unique feature, MPBEC includes a useful graphical user interface (GUI) application which helps and guides users to configure and setup the optimal parameters and approximations to successfully perform the required biomolecular electrostatic calculations. The GUI also incorporates visualization tools to facilitate users pre- and post- analysis of structural and electrical properties of biomolecules.

  7. Selected topics in solution-phase biomolecular NMR spectroscopy

    Science.gov (United States)

    Kay, Lewis E.; Frydman, Lucio

    2017-05-01

    Solution bio-NMR spectroscopy continues to enjoy a preeminent role as an important tool in elucidating the structure and dynamics of a range of important biomolecules and in relating these to function. Equally impressive is how NMR continues to 'reinvent' itself through the efforts of many brilliant practitioners who ask increasingly demanding and increasingly biologically relevant questions. The ability to manipulate spin Hamiltonians - almost at will - to dissect the information of interest contributes to the success of the endeavor and ensures that the NMR technology will be well poised to contribute to as yet unknown frontiers in the future. As a tribute to the versatility of solution NMR in biomolecular studies and to the continued rapid advances in the field we present a Virtual Special Issue (VSI) that includes over 40 articles on various aspects of solution-state biomolecular NMR that have been published in the Journal of Magnetic Resonance in the past 7 years. These, in total, help celebrate the achievements of this vibrant field.

  8. Analysis of biomolecular interactions using affinity microcolumns: A review

    Science.gov (United States)

    Zheng, Xiwei; Li, Zhao; Beeram, Sandya; Podariu, Maria; Matsuda, Ryan; Pfaunmiller, Erika L.; White, Christopher J.; Carter, NaTasha; Hage, David S.

    2014-01-01

    Affinity chromatography has become an important tool for characterizing biomolecular interactions. The use of affinity microcolumns, which contain immobilized binding agents and have volumes in the mid-to-low microliter range, has received particular attention in recent years. Potential advantages of affinity microcolumns include the many analysis and detection formats that can be used with these columns, as well as the need for only small amounts of supports and immobilized binding agents. This review examines how affinity microcolumns have been used to examine biomolecular interactions. Both capillary-based microcolumns and short microcolumns are considered. The use of affinity microcolumns with zonal elution and frontal analysis methods are discussed. The techniques of peak decay analysis, ultrafast affinity extraction, split-peak analysis, and band-broadening studies are also explored. The principles of these methods are examined and various applications are provided to illustrate the use of these methods with affinity microcolumns. It is shown how these techniques can be utilized to provide information on the binding strength and kinetics of an interaction, as well as on the number and types of binding sites. It is further demonstrated how information on competition or displacement effects can be obtained by these methods. PMID:24572459

  9. MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations

    Science.gov (United States)

    Vergara-Perez, Sandra; Marucho, Marcelo

    2016-01-01

    One of the most used and efficient approaches to compute electrostatic properties of biological systems is to numerically solve the Poisson-Boltzmann (PB) equation. There are several software packages available that solve the PB equation for molecules in aqueous electrolyte solutions. Most of these software packages are useful for scientists with specialized training and expertise in computational biophysics. However, the user is usually required to manually take several important choices, depending on the complexity of the biological system, to successfully obtain the numerical solution of the PB equation. This may become an obstacle for researchers, experimentalists, even students with no special training in computational methodologies. Aiming to overcome this limitation, in this article we present MPBEC, a free, cross-platform, open-source software that provides non-experts in the field an easy and efficient way to perform biomolecular electrostatic calculations on single processor computers. MPBEC is a Matlab script based on the Adaptative Poisson-Boltzmann Solver, one of the most popular approaches used to solve the PB equation. MPBEC does not require any user programming, text editing or extensive statistical skills, and comes with detailed user-guide documentation. As a unique feature, MPBEC includes a useful graphical user interface (GUI) application which helps and guides users to configure and setup the optimal parameters and approximations to successfully perform the required biomolecular electrostatic calculations. The GUI also incorporates visualization tools to facilitate users pre- and post-analysis of structural and electrical properties of biomolecules.

  10. Bayesian Modeling of Biomolecular Assemblies with Cryo-EM Maps.

    Science.gov (United States)

    Habeck, Michael

    2017-01-01

    A growing array of experimental techniques allows us to characterize the three-dimensional structure of large biological assemblies at increasingly higher resolution. In addition to X-ray crystallography and nuclear magnetic resonance in solution, new structure determination methods such cryo-electron microscopy (cryo-EM), crosslinking/mass spectrometry and solid-state NMR have emerged. Often it is not sufficient to use a single experimental method, but complementary data need to be collected by using multiple techniques. The integration of all datasets can only be achieved by computational means. This article describes Inferential structure determination, a Bayesian approach to integrative modeling of biomolecular complexes with hybrid structural data. I will introduce probabilistic models for cryo-EM maps and outline Markov chain Monte Carlo algorithms for sampling model structures from the posterior distribution. I will focus on rigid and flexible modeling with cryo-EM data and discuss some of the computational challenges of Bayesian inference in the context of biomolecular modeling.

  11. Data-driven coarse graining of large biomolecular structures.

    Science.gov (United States)

    Chen, Yi-Ling; Habeck, Michael

    2017-01-01

    Advances in experimental and computational techniques allow us to study the structure and dynamics of large biomolecular assemblies at increasingly higher resolution. However, with increasing structural detail it can be challenging to unravel the mechanism underlying the function of molecular machines. One reason is that atomistic simulations become computationally prohibitive. Moreover it is difficult to rationalize the functional mechanism of systems composed of tens of thousands to millions of atoms by following each atom's movements. Coarse graining (CG) allows us to understand biological structures from a hierarchical perspective and to gradually zoom into the adequate level of structural detail. This article introduces a Bayesian approach for coarse graining biomolecular structures. We develop a probabilistic model that aims to represent the shape of an experimental structure as a cloud of bead particles. The particles interact via a pairwise potential whose parameters are estimated along with the bead positions and the CG mapping between atoms and beads. Our model can also be applied to density maps obtained by cryo-electron microscopy. We illustrate our approach on various test systems.

  12. On the origin of the anomalous ultraslow solvation dynamics in ...

    Indian Academy of Sciences (India)

    TECS

    –1 compared to bulk water. 23. From temperature variation of solvation dynamics in a triton X-100 (TX) micelle has been found to involve an activation energy of 9 kcal mol. –1 and a positive entropy of activation. 23. However, al- though, the dynamic exchange model is adequate to explain the slow component in 30–500 ps ...

  13. Structural Interactions within Lithium Salt Solvates. Acyclic Carbonates and Esters

    Energy Technology Data Exchange (ETDEWEB)

    Afroz, Taliman [North Carolina State Univ., Raleigh, NC (United States); Seo, D. M. [North Carolina State Univ., Raleigh, NC (United States); Han, Sang D. [North Carolina State Univ., Raleigh, NC (United States); Boyle, Paul D. [North Carolina State Univ., Raleigh, NC (United States); Henderson, Wesley A. [North Carolina State Univ., Raleigh, NC (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-03-06

    Solvate crystal structures serve as useful models for the molecular-level interactions within the diverse solvates present in liquid electrolytes. Although acyclic carbonate solvents are widely used for Li-ion battery electrolytes, only three solvate crystal structures with lithium salts are known for these and related solvents. The present work, therefore, reports six lithium salt solvate structures with dimethyl and diethyl carbonate: (DMC)2:LiPF6, (DMC)1:LiCF3SO3, (DMC)1/4:LiBF4, (DEC)2:LiClO4, (DEC)1:LiClO4 and (DEC)1:LiCF3SO3 and four with the structurally related methyl and ethyl acetate: (MA)2:LiClO4, (MA)1:LiBF4, (EA)1:LiClO4 and (EA)1:LiBF4.

  14. Microscopic picture of the aqueous solvation of glutamic acid

    NARCIS (Netherlands)

    Leenders, E.J.M.; Bolhuis, P.G.; Meijer, E.J.

    2008-01-01

    We present molecular dynamics simulations of glutamic acid and glutamate solvated in water, using both density functional theory (DFT) and the Gromos96 force field. We focus on the microscopic aspects of the solvation−particularly on the hydrogen bond structures and dynamics−and investigate the

  15. PREFACE: Radiation Damage in Biomolecular Systems (RADAM07)

    Science.gov (United States)

    McGuigan, Kevin G.

    2008-03-01

    The annual meeting of the COST P9 Action `Radiation damage in biomolecular systems' took place from 19-22 June 2007 in the Royal College of Surgeons in Ireland, in Dublin. The conference was structured into 5 Working Group sessions: Electrons and biomolecular interactions Ions and biomolecular interactions Radiation in physiological environments Theoretical developments for radiation damage Track structure in cells Each of the five working groups presented two sessions of invited talks. Professor Ron Chesser of Texas Tech University, USA gave a riveting plenary talk on `Mechanisms of Adaptive Radiation Responses in Mammals at Chernobyl' and the implications his work has on the Linear-No Threshold model of radiation damage. In addition, this was the first RADAM meeting to take place after the Alexander Litvenenko affair and we were fortunate to have one of the leading scientists involved in the European response Professor Herwig Paretzke of GSF-Institut für Strahlenschutz, Neuherberg, Germany, available to speak. The remaining contributions were presented in the poster session. A total of 72 scientific contributions (32 oral, 40 poster), presented by 97 participants from 22 different countries, gave an overview on the current progress in the 5 different subfields. A 1-day pre-conference `Early Researcher Tutorial Workshop' on the same topic kicked off on 19 June attended by more than 40 postgrads, postdocs and senior researchers. Twenty papers, based on these reports, are included in this volume of Journal of Physics: Conference Series. All the contributions in this volume were fully refereed, and they represent a sample of the courses, invited talks and contributed talks presented during RADAM07. The interdisciplinary RADAM07 conference brought together researchers from a variety of different fields with a common interest in biomolecular radiation damage. This is reflected by the disparate backgrounds of the authors of the papers presented in these proceedings

  16. Multiparametric Atomic Force Microscopy Imaging of Biomolecular and Cellular Systems.

    Science.gov (United States)

    Alsteens, David; Müller, Daniel J; Dufrêne, Yves F

    2017-04-18

    There is a need in biochemical research for new tools that can image and manipulate biomolecular and cellular systems at the nanoscale. During the past decades, there has been tremendous progress in developing atomic force microscopy (AFM) techniques to analyze biosystems, down to the single-molecule level. Force-distance (FD) curve-based AFM in particular has enabled researchers to map and quantify biophysical properties and biomolecular interactions on a wide variety of specimens. Despite its great potential, this AFM method has long been limited by its low spatial and temporal resolutions. Recently, novel FD-based multiparametric imaging modalities have been developed, allowing us to simultaneously image the structure, elasticity and interactions of biological samples at high spatiotemporal resolution. By oscillating the AFM tip, spatially resolved FD curves are obtained at much higher frequency than before, and as a result, samples are mapped at a speed similar to that of conventional topographic imaging. In this Account, we discuss the general principle of multiparametric AFM imaging and we provide a snapshot of recent studies showing how this new technology has been applied to biological specimens, from soluble proteins to membranes and cells. We emphasize novel methodologies that we recently developed, in which multiparametric imaging is combined with probes functionalized with chemical groups, ligands, or even live cells, in order to image and quantify receptor interaction forces and free-energy landscapes in a way not possible before. Key breakthroughs include observing the mechanical and chemical properties of single proteins in purple membranes, measuring the electrostatic potential of transmembrane pore forming proteins, structurally localizing chemical groups of water-soluble proteins, mapping and nanomechanical analysis of single sensors on yeast cells, imaging the sites of assembly and extrusion of single filamentous bacteriophages in living bacteria

  17. Parallel Explicit and Implicit Control of Reaching

    OpenAIRE

    Pietro Mazzoni; Wexler, Nancy S

    2009-01-01

    Background Human movement can be guided automatically (implicit control) or attentively (explicit control). Explicit control may be engaged when learning a new movement, while implicit control enables simultaneous execution of multiple actions. Explicit and implicit control can often be assigned arbitrarily: we can simultaneously drive a car and tune the radio, seamlessly allocating implicit or explicit control to either action. This flexibility suggests that sensorimotor signals, including t...

  18. Solvates of the antifungal drug griseofulvin: structural, thermochemical and conformational analysis.

    Science.gov (United States)

    Aitipamula, Srinivasulu; Chow, Pui Shan; Tan, Reginald B H

    2014-02-01

    Four solvates of an antifungal drug, griseofulvin (GF), were discovered. All the solvates were characterized by differential scanning calorimetry, thermogravimetric analysis, and their crystal structures were determined by single-crystal X-ray diffraction. The solvents that form the solvates are acetonitrile, nitromethane and nitroethane (2:1 and 1:1). It was found that all the solvates lose the solvent molecules from the crystal lattice between 343 and 383 K, and that the melting point of the desolvated materials matched the melting point of the solvent-free GF (493 K). The conformation of the GF molecule in solvent-free form was found to be significantly different from the conformations found in the solvates. Solution stability studies revealed that the GF-acetonitrile solvate transforms to GF and that GF-nitroethane (1:1) solvate transforms to GF-nitroethane (2:1) solvate. On the other hand, GF-nitromethane and GF-nitroethane (2:1) solvates were found to be stable in solution. Our results highlight the importance of the co-crystallization technique in the pharmaceutical drug development; it not only expands the solid form diversity but also creates new avenues for unraveling novel solvates.

  19. Architecture of transcriptional regulatory circuits is knitted over the topology of bio-molecular interaction networks

    DEFF Research Database (Denmark)

    Soberano de Oliveira, Ana Paula; Patil, Kiran Raosaheb; Nielsen, Jens

    2008-01-01

    is to use the topology of bio-molecular interaction networks in order to constrain the solution space. Such approaches systematically integrate the existing biological knowledge with the 'omics' data. Results: Here we introduce a hypothesis-driven method that integrates bio-molecular network topology...... Factors, Reporter Proteins and Reporter Complexes, and use this to decipher the logic of regulatory circuits playing a key role in yeast glucose repression and human diabetes. Conclusion: Reporter Features offer the opportunity to identify regulatory hot-spots in bio-molecular interaction networks...

  20. Managing biological complexity across orthologs with a visual knowledgebase of documented biomolecular interactions.

    Science.gov (United States)

    Vanburen, Vincent; Chen, Hailin

    2012-01-01

    The complexity of biomolecular interactions and influences is a major obstacle to their comprehension and elucidation. Visualizing knowledge of biomolecular interactions increases comprehension and facilitates the development of new hypotheses. The rapidly changing landscape of high-content experimental results also presents a challenge for the maintenance of comprehensive knowledgebases. Distributing the responsibility for maintenance of a knowledgebase to a community of subject matter experts is an effective strategy for large, complex and rapidly changing knowledgebases. Cognoscente serves these needs by building visualizations for queries of biomolecular interactions on demand, by managing the complexity of those visualizations, and by crowdsourcing to promote the incorporation of current knowledge from the literature.

  1. Biomolecular Simulation of Base Excision Repair and Protein Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Straatsma, TP; McCammon, J A; Miller, John H; Smith, Paul E; Vorpagel, Erich R; Wong, Chung F; Zacharias, Martin W

    2006-03-03

    The goal of the Biomolecular Simulation of Base Excision Repair and Protein Signaling project is to enhance our understanding of the mechanism of human polymerase-β, one of the key enzymes in base excision repair (BER) and the cell-signaling enzymes cyclic-AMP-dependent protein kinase. This work used molecular modeling and simulation studies to specifically focus on the • dynamics of DNA and damaged DNA • dynamics and energetics of base flipping in DNA • mechanism and fidelity of nucleotide insertion by BER enzyme human polymerase-β • mechanism and inhibitor design for cyclic-AMP-dependent protein kinase. Molecular dynamics simulations and electronic structure calculations have been performed using the computer resources at the Molecular Science Computing Facility at the Environmental Molecular Sciences Laboratory.

  2. Identification of Receptor Binding to the Biomolecular Corona of Nanoparticles.

    Science.gov (United States)

    Lara, Sandra; Alnasser, Fatima; Polo, Ester; Garry, David; Lo Giudice, Maria Cristina; Hristov, Delyan R; Rocks, Louise; Salvati, Anna; Yan, Yan; Dawson, Kenneth A

    2017-02-28

    Biomolecules adsorbed on nanoparticles are known to confer a biological identity to nanoparticles, mediating the interactions with cells and biological barriers. However, how these molecules are presented on the particle surface in biological milieu remains unclear. The central aim of this study is to identify key protein recognition motifs and link them to specific cell-receptor interactions. Here, we employed an immuno-mapping technique to quantify epitope presentations of two major proteins in the serum corona, low-density lipoprotein and immunoglobulin G. Combining with a purpose-built receptor expression system, we show that both proteins present functional motifs to allow simultaneous recognition by low-density lipoprotein receptor and Fc-gamma receptor I of the corona. Our results suggest that the "labeling" of nanoparticles by biomolecular adsorption processes allows for multiple pathways in biological processes in which they may be "mistaken" for endogenous objects, such as lipoproteins, and exogenous ones, such as viral infections.

  3. Design and implementation of a biomolecular concentration tracker.

    Science.gov (United States)

    Hsiao, Victoria; de los Santos, Emmanuel L C; Whitaker, Weston R; Dueber, John E; Murray, Richard M

    2015-02-20

    As a field, synthetic biology strives to engineer increasingly complex artificial systems in living cells. Active feedback in closed loop systems offers a dynamic and adaptive way to ensure constant relative activity independent of intrinsic and extrinsic noise. In this work, we use synthetic protein scaffolds as a modular and tunable mechanism for concentration tracking through negative feedback. Input to the circuit initiates scaffold production, leading to colocalization of a two-component system and resulting in the production of an inhibitory antiscaffold protein. Using a combination of modeling and experimental work, we show that the biomolecular concentration tracker circuit achieves dynamic protein concentration tracking in Escherichia coli and that steady state outputs can be tuned.

  4. Review of MEMS differential scanning calorimetry for biomolecular study

    Science.gov (United States)

    Yu, Shifeng; Wang, Shuyu; Lu, Ming; Zuo, Lei

    2017-12-01

    Differential scanning calorimetry (DSC) is one of the few techniques that allow direct determination of enthalpy values for binding reactions and conformational transitions in biomolecules. It provides the thermodynamics information of the biomolecules which consists of Gibbs free energy, enthalpy and entropy in a straightforward manner that enables deep understanding of the structure function relationship in biomolecules such as the folding/unfolding of protein and DNA, and ligand bindings. This review provides an up to date overview of the applications of DSC in biomolecular study such as the bovine serum albumin denaturation study, the relationship between the melting point of lysozyme and the scanning rate. We also introduce the recent advances of the development of micro-electro-mechanic-system (MEMS) based DSCs.

  5. Processivity and collectivity of biomolecular motors extracting membrane nanotubes

    Science.gov (United States)

    Fontenele Araujo, Francisco; Storm, Cornelis

    2012-07-01

    Biomolecular motors can pull and viscously drag membranes. The resulting elongations include cell protrusions, tether networks, and sensorial tentacles. Here we focus on the extraction of a single tube from a vesicle. Via a force balance coupled to binding kinetics, we analytically determine the phase diagram of tube formation as function of the motor processivity, the surface viscosity of the membrane ηm', and the density of motors on the vesicle ρ. Three tubulation mechanisms are identified: (i) tip pulling, due to the accumulation of motors at the leading edge of the membrane, (ii) viscous drag, emergent from the translation of motors along the tube, and (iii) hybrid extraction, such that tip pulling and viscous drag are equally important. For experimental values of ηm' and ρ, we find that the growth of bionanotubes tends to be driven by viscous forces, whereas artificial membranes are dominated by tip pulling.

  6. Design rules for biomolecular adhesion: lessons from force measurements.

    Science.gov (United States)

    Leckband, Deborah

    2010-01-01

    Cell adhesion to matrix, other cells, or pathogens plays a pivotal role in many processes in biomolecular engineering. Early macroscopic methods of quantifying adhesion led to the development of quantitative models of cell adhesion and migration. The more recent use of sensitive probes to quantify the forces that alter or manipulate adhesion proteins has revealed much greater functional diversity than was apparent from population average measurements of cell adhesion. This review highlights theoretical and experimental methods that identified force-dependent molecular properties that are central to the biological activity of adhesion proteins. Experimental and theoretical methods emphasized in this review include the surface force apparatus, atomic force microscopy, and vesicle-based probes. Specific examples given illustrate how these tools have revealed unique properties of adhesion proteins and their structural origins.

  7. Review of MEMS differential scanning calorimetry for biomolecular study

    Science.gov (United States)

    Yu, Shifeng; Wang, Shuyu; Lu, Ming; Zuo, Lei

    2017-07-01

    Differential scanning calorimetry (DSC) is one of the few techniques that allow direct determination of enthalpy values for binding reactions and conformational transitions in biomolecules. It provides the thermodynamics information of the biomolecules which consists of Gibbs free energy, enthalpy and entropy in a straightforward manner that enables deep understanding of the structure function relationship in biomolecules such as the folding/unfolding of protein and DNA, and ligand bindings. This review provides an up to date overview of the applications of DSC in biomolecular study such as the bovine serum albumin denaturation study, the relationship between the melting point of lysozyme and the scanning rate. We also introduce the recent advances of the development of micro-electro-mechanic-system (MEMS) based DSCs.

  8. Evolution of a magnetic-based biomolecular detection system.

    Science.gov (United States)

    Tamanaha, Cy R; Mulvaney, Shawn P; Rife, Jack C

    2009-01-01

    Amongst the plethora of affinity biosensor systems based on biomolecular recognition and labeling assays, magnetic labeling and detection has emerged as a promising approach. Magnetic labels can be detected by a wide range of non-invasive methods, are physically and chemically stable, relatively inexpensive to produce, and can be easily made biocompatible. Over a decade ago, the U. S. Naval Research Laboratory pioneered the use of giant magnetoresistive (GMR) sensors to detect biomolecules labeled with paramagnetic microbeads. Since then, our various investigations and engineering efforts have resulted in significant improvements in both the magnetoelectronic instrumentation and the assays associated with these magnetic labels. This paper and subsequent presentation provides a synopsis of the development of our technology which has evolved into a highly sensitive detection method.

  9. Applied Graph-Mining Algorithms to Study Biomolecular Interaction Networks

    Science.gov (United States)

    2014-01-01

    Protein-protein interaction (PPI) networks carry vital information on the organization of molecular interactions in cellular systems. The identification of functionally relevant modules in PPI networks is one of the most important applications of biological network analysis. Computational analysis is becoming an indispensable tool to understand large-scale biomolecular interaction networks. Several types of computational methods have been developed and employed for the analysis of PPI networks. Of these computational methods, graph comparison and module detection are the two most commonly used strategies. This review summarizes current literature on graph kernel and graph alignment methods for graph comparison strategies, as well as module detection approaches including seed-and-extend, hierarchical clustering, optimization-based, probabilistic, and frequent subgraph methods. Herein, we provide a comprehensive review of the major algorithms employed under each theme, including our recently published frequent subgraph method, for detecting functional modules commonly shared across multiple cancer PPI networks. PMID:24800226

  10. Mapping protein binding sites on the biomolecular corona of nanoparticles

    Science.gov (United States)

    Kelly, Philip M.; Åberg, Christoffer; Polo, Ester; O'Connell, Ann; Cookman, Jennifer; Fallon, Jonathan; Krpetić, Željka; Dawson, Kenneth A.

    2015-05-01

    Nanoparticles in a biological milieu are known to form a sufficiently long-lived and well-organized ‘corona’ of biomolecules to confer a biological identity to the particle. Because this nanoparticle-biomolecule complex interacts with cells and biological barriers, potentially engaging with different biological pathways, it is important to clarify the presentation of functional biomolecular motifs at its interface. Here, we demonstrate that by using antibody-labelled gold nanoparticles, differential centrifugal sedimentation and various imaging techniques it is possible to identify the spatial location of proteins, their functional motifs and their binding sites. We show that for transferrin-coated polystyrene nanoparticles only a minority of adsorbed proteins exhibit functional motifs and the spatial organization appears random, which is consistent, overall, with a stochastic and irreversible adsorption process. Our methods are applicable to a wide array of nanoparticles and can offer a microscopic molecular description of the biological identity of nanoparticles.

  11. The biomolecular corona of nanoparticles in circulating biological media

    Science.gov (United States)

    Pozzi, D.; Caracciolo, G.; Digiacomo, L.; Colapicchioni, V.; Palchetti, S.; Capriotti, A. L.; Cavaliere, C.; Zenezini Chiozzi, R.; Puglisi, A.; Laganà, A.

    2015-08-01

    When nanoparticles come into contact with biological media, they are covered by a biomolecular `corona', which confers a new identity to the particles. In all the studies reported so far nanoparticles are incubated with isolated plasma or serum that are used as a model for protein adsorption. Anyway, bodily fluids are dynamic in nature so the question arises on whether the incubation protocol, i.e. dynamic vs. static incubation, could affect the composition and structure of the biomolecular corona. Here we let multicomponent liposomes interact with fetal bovine serum (FBS) both statically and dynamically, i.e. in contact with circulating FBS (~40 cm s-1). The structure and composition of the liposome-protein corona, as determined by dynamic light scattering, electrophoretic light scattering and liquid chromatography tandem mass spectrometry, were found to be dependent on the incubation protocol. Specifically, following dynamic exposure to FBS, multicomponent liposomes were less enriched in complement proteins and appreciably more enriched in apolipoproteins and acute phase proteins (e.g. alpha-1-antitrypsin and inter-alpha-trypsin inhibitor heavy chain H3) that are involved in relevant interactions between nanoparticles and living systems. Supported by our results, we speculate that efficient predictive modeling of nanoparticle behavior in vivo will require accurate knowledge of nanoparticle-specific protein fingerprints in circulating biological media.When nanoparticles come into contact with biological media, they are covered by a biomolecular `corona', which confers a new identity to the particles. In all the studies reported so far nanoparticles are incubated with isolated plasma or serum that are used as a model for protein adsorption. Anyway, bodily fluids are dynamic in nature so the question arises on whether the incubation protocol, i.e. dynamic vs. static incubation, could affect the composition and structure of the biomolecular corona. Here we let

  12. Computational and theoretical aspects of biomolecular structure and dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, A.E.; Berendzen, J.; Catasti, P., Chen, X. [and others

    1996-09-01

    This is the final report for a project that sought to evaluate and develop theoretical, and computational bases for designing, performing, and analyzing experimental studies in structural biology. Simulations of large biomolecular systems in solution, hydrophobic interactions, and quantum chemical calculations for large systems have been performed. We have developed a code that implements the Fast Multipole Algorithm (FMA) that scales linearly in the number of particles simulated in a large system. New methods have been developed for the analysis of multidimensional NMR data in order to obtain high resolution atomic structures. These methods have been applied to the study of DNA sequences in the human centromere, sequences linked to genetic diseases, and the dynamics and structure of myoglobin.

  13. Biomolecular detection with an interferometric microfiber-capillary optofluidic sensor

    Science.gov (United States)

    Liang, Lili; Jin, Long; Guan, Bai-Ou

    2017-04-01

    We have developed a chip-scale optofluidic sensor for biomolecular detection, by tapering laterally aligned silica microfiber and capillary to form a modal interferometer. With the pre-immobilization of DNA probes, the sensor is capable of selectively detecting single-stranded microRNA-let7a (molecular weight: 6.5 k) by measuring the spectral shift of the interferometric spectrum. A log-linear response from 2 nM to 20 μM and a minimum detectable concentration of 212 pM (1.43 ng/mL) have been achieved. The sensor is promising for future diagnosis applications due to its high sensitivity, resistance to environmental perturbations, improved portability, and intrinsic connection to fiber optic measurement.

  14. Integration of biomolecular logic gates with field-effect transducers

    Energy Technology Data Exchange (ETDEWEB)

    Poghossian, A., E-mail: a.poghossian@fz-juelich.de [Institute of Nano- and Biotechnologies, Aachen University of Applied Sciences, Campus Juelich, Heinrich-Mussmann-Str. 1, D-52428 Juelich (Germany); Institute of Bio- and Nanosystems, Research Centre Juelich GmbH, D-52425 Juelich (Germany); Malzahn, K. [Institute of Nano- and Biotechnologies, Aachen University of Applied Sciences, Campus Juelich, Heinrich-Mussmann-Str. 1, D-52428 Juelich (Germany); Abouzar, M.H. [Institute of Nano- and Biotechnologies, Aachen University of Applied Sciences, Campus Juelich, Heinrich-Mussmann-Str. 1, D-52428 Juelich (Germany); Institute of Bio- and Nanosystems, Research Centre Juelich GmbH, D-52425 Juelich (Germany); Mehndiratta, P. [Institute of Nano- and Biotechnologies, Aachen University of Applied Sciences, Campus Juelich, Heinrich-Mussmann-Str. 1, D-52428 Juelich (Germany); Katz, E. [Department of Chemistry and Biomolecular Science, NanoBio Laboratory (NABLAB), Clarkson University, Potsdam, NY 13699-5810 (United States); Schoening, M.J. [Institute of Nano- and Biotechnologies, Aachen University of Applied Sciences, Campus Juelich, Heinrich-Mussmann-Str. 1, D-52428 Juelich (Germany); Institute of Bio- and Nanosystems, Research Centre Juelich GmbH, D-52425 Juelich (Germany)

    2011-11-01

    Highlights: > Enzyme-based AND/OR logic gates are integrated with a capacitive field-effect sensor. > The AND/OR logic gates compose of multi-enzyme system immobilised on sensor surface. > Logic gates were activated by different combinations of chemical inputs (analytes). > The logic output (pH change) produced by the enzymes was read out by the sensor. - Abstract: The integration of biomolecular logic gates with field-effect devices - the basic element of conventional electronic logic gates and computing - is one of the most attractive and promising approaches for the transformation of biomolecular logic principles into macroscopically useable electrical output signals. In this work, capacitive field-effect EIS (electrolyte-insulator-semiconductor) sensors based on a p-Si-SiO{sub 2}-Ta{sub 2}O{sub 5} structure modified with a multi-enzyme membrane have been used for electronic transduction of biochemical signals processed by enzyme-based OR and AND logic gates. The realised OR logic gate composes of two enzymes (glucose oxidase and esterase) and was activated by ethyl butyrate or/and glucose. The AND logic gate composes of three enzymes (invertase, mutarotase and glucose oxidase) and was activated by two chemical input signals: sucrose and dissolved oxygen. The developed integrated enzyme logic gates produce local pH changes at the EIS sensor surface as a result of biochemical reactions activated by different combinations of chemical input signals, while the pH value of the bulk solution remains unchanged. The pH-induced charge changes at the gate-insulator (Ta{sub 2}O{sub 5}) surface of the EIS transducer result in an electronic signal corresponding to the logic output produced by the immobilised enzymes. The logic output signals have been read out by means of a constant-capacitance method.

  15. Electrostatics in Biomolecular Interactions: a Surface Charge Method

    Science.gov (United States)

    Yu, Yi-Kuo

    2005-03-01

    Biomolecular interactions determine how transcription factors recognize their DNA binding sites, how proteins interact with each other, and consequently how a biological system functions. Since both proteins and DNAs are significantly charged, electrostatic interactions are among the most important when studying biomolecular interactions. Although the fundamental equations for electrostatics are known, the solution in low symmetry situations with a high dielectric constant solvent (e.g. water) can be difficult to obtain in an appropriate form and with an acceptable degree of accuracy and amount of computation. In order to compute the electrostatic force, each atom is usually modeled as a dielectric sphere with a point charge at its center. Even the case of two spheres is non-trivial. The energetic calculations of such a system are still very crude and lack systematic control of accuracy. To establish a scheme where accuracy of the computation can be controlled systematically, we have established a new formulation where the surface charge distribution is used as a new variable. The surface charge has the advantage of reducing the number of degrees of freedom (from 3D to 2D), can accommodate the presence of ions, and is applicable to arbitrary geometrical shapes. The Poisson-Boltzmann equation is currently the most popular approach in dealing with ionic effects. This approach, unfortunately, suffers from several drawbacks. In this talk, I will describe these drawbacks in slightly more detail, and describe possible methods to circumvent these problems. The solution for general geometrical shapes can be obtained numerically by choosing a tiling of the surface and solving a corresponding set of linear algebraic equations (the finite-element method). These equations can be efficiently solved numerically for use in molecular dynamics simulations.

  16. SIRAH: a structurally unbiased coarse-grained force field for proteins with aqueous solvation and long-range electrostatics.

    Science.gov (United States)

    Darré, Leonardo; Machado, Matías Rodrigo; Brandner, Astrid Febe; González, Humberto Carlos; Ferreira, Sebastián; Pantano, Sergio

    2015-02-10

    Modeling of macromolecular structures and interactions represents an important challenge for computational biology, involving different time and length scales. However, this task can be facilitated through the use of coarse-grained (CG) models, which reduce the number of degrees of freedom and allow efficient exploration of complex conformational spaces. This article presents a new CG protein model named SIRAH, developed to work with explicit solvent and to capture sequence, temperature, and ionic strength effects in a topologically unbiased manner. SIRAH is implemented in GROMACS, and interactions are calculated using a standard pairwise Hamiltonian for classical molecular dynamics simulations. We present a set of simulations that test the capability of SIRAH to produce a qualitatively correct solvation on different amino acids, hydrophilic/hydrophobic interactions, and long-range electrostatic recognition leading to spontaneous association of unstructured peptides and stable structures of single polypeptides and protein-protein complexes.

  17. Parallel explicit and implicit control of reaching.

    Science.gov (United States)

    Mazzoni, Pietro; Wexler, Nancy S

    2009-10-22

    Human movement can be guided automatically (implicit control) or attentively (explicit control). Explicit control may be engaged when learning a new movement, while implicit control enables simultaneous execution of multiple actions. Explicit and implicit control can often be assigned arbitrarily: we can simultaneously drive a car and tune the radio, seamlessly allocating implicit or explicit control to either action. This flexibility suggests that sensorimotor signals, including those that encode spatially overlapping perception and behavior, can be accurately segregated to explicit and implicit control processes. We tested human subjects' ability to segregate sensorimotor signals to parallel control processes by requiring dual (explicit and implicit) control of the same reaching movement and testing for interference between these processes. Healthy control subjects were able to engage dual explicit and implicit motor control without degradation of performance compared to explicit or implicit control alone. We then asked whether segregation of explicit and implicit motor control can be selectively disrupted by studying dual-control performance in subjects with no clinically manifest neurologic deficits in the presymptomatic stage of Huntington's disease (HD). These subjects performed successfully under either explicit or implicit control alone, but were impaired in the dual-control condition. The human nervous system can exert dual control on a single action, and is therefore able to accurately segregate sensorimotor signals to explicit and implicit control. The impairment observed in the presymptomatic stage of HD points to a possible crucial contribution of the striatum to the segregation of sensorimotor signals to multiple control processes.

  18. Parallel explicit and implicit control of reaching.

    Directory of Open Access Journals (Sweden)

    Pietro Mazzoni

    2009-10-01

    Full Text Available Human movement can be guided automatically (implicit control or attentively (explicit control. Explicit control may be engaged when learning a new movement, while implicit control enables simultaneous execution of multiple actions. Explicit and implicit control can often be assigned arbitrarily: we can simultaneously drive a car and tune the radio, seamlessly allocating implicit or explicit control to either action. This flexibility suggests that sensorimotor signals, including those that encode spatially overlapping perception and behavior, can be accurately segregated to explicit and implicit control processes.We tested human subjects' ability to segregate sensorimotor signals to parallel control processes by requiring dual (explicit and implicit control of the same reaching movement and testing for interference between these processes. Healthy control subjects were able to engage dual explicit and implicit motor control without degradation of performance compared to explicit or implicit control alone. We then asked whether segregation of explicit and implicit motor control can be selectively disrupted by studying dual-control performance in subjects with no clinically manifest neurologic deficits in the presymptomatic stage of Huntington's disease (HD. These subjects performed successfully under either explicit or implicit control alone, but were impaired in the dual-control condition.The human nervous system can exert dual control on a single action, and is therefore able to accurately segregate sensorimotor signals to explicit and implicit control. The impairment observed in the presymptomatic stage of HD points to a possible crucial contribution of the striatum to the segregation of sensorimotor signals to multiple control processes.

  19. A molecular density functional theory to study solvation in water

    CERN Document Server

    Jeanmairet, Guillaume

    2014-01-01

    A classical density functional theory is applied to study solvation of solutes in water. An approx- imate form of the excess functional is proposed for water. This functional requires the knowledge of pure solvent direct correlation functions. Those functions can be computed by using molecular simulations such as molecular dynamic or Monte Carlo. It is also possible to use functions that have been determined experimentally. The functional minimization gives access to the solvation free energy and to the equilibrium solvent density. Some correction to the functional are also proposed to get the proper tetrahedral order of solvent molecules around a charged solute and to reproduce the correct long range hydrophobic behavior of big apolar solutes. To proceed the numerical minimization of the functional, the theory has been discretized on two tridimensional grids, one for the space coordinates, the other for the angular coordinates, in a functional minimization code written in modern Fortran, mdft. This program i...

  20. IONIC LIQUIDS: RADIATION CHEMISTRY, SOLVATION DYNAMICS AND REACTIVITY PATTERNS.

    Energy Technology Data Exchange (ETDEWEB)

    WISHART,J.F.

    2007-10-01

    energy production, nuclear fuel and waste processing, improving the efficiency and safety of industrial chemical processes, and pollution prevention. ILs are generally nonvolatile, noncombustible, highly conductive, recyclable and capable of dissolving a wide variety of materials. They are finding new uses in chemical synthesis, catalysis, separations chemistry, electrochemistry and other areas. Ionic liquids have dramatically different properties compared to conventional molecular solvents, and they provide a new and unusual environment to test our theoretical understanding of charge transfer and other reactions. We are interested in how IL properties influence physical and dynamical processes that determine the stability and lifetimes of reactive intermediates and thereby affect the courses of chemical reactions and product distributions. Successful use of ionic liquids in radiation-filled environments, where their safety advantages could be significant, requires an understanding of ionic liquid radiation chemistry. For example, characterizing the primary steps of IL radiolysis will reveal radiolytic degradation pathways and suggest ways to prevent them or mitigate their effects on the properties of the material. An understanding of ionic liquid radiation chemistry will also facilitate pulse radiolysis studies of general chemical reactivity in ILs, which will aid in the development of applications listed above. Very early in our radiolysis studies it became evident that slow solvation dynamics of the excess electron in ILs (which vary over a wide viscosity range) increases the importance of pre-solvated electron reactivity and consequently alters product distributions. Parallel studies of IL solvation phenomena using coumarin-153 dynamic Stokes shifts and polarization anisotropy decay rates are done to compare with electron solvation studies and to evaluate the influence of ILs on charge transport processes. Methods. Picosecond pulse radiolysis studies at BNL

  1. Ionic Liquids: Radiation Chemistry, Solvation Dynamics and Reactivity Patterns

    Energy Technology Data Exchange (ETDEWEB)

    Wishart,J.F.

    2008-09-29

    Ionic liquids (ILs) are a rapidly expanding family of condensed-phase media with important applications in energy production, nuclear fuel and waste processing, improving the efficiency and safety of industrial chemical processes, and pollution prevention. ILs are generally nonvolatile, noncombustible, highly conductive, recyclable and capable of dissolving a wide variety of materials. They are finding new uses in chemical synthesis, catalysis, separations chemistry, electrochemistry and other areas. Ionic liquids have dramatically different properties compared to conventional molecular solvents, and they provide a new and unusual environment to test our theoretical understanding of charge transfer and other reactions. We are interested in how IL properties influence physical and dynamical processes that determine the stability and lifetimes of reactive intermediates and thereby affect the courses of chemical reactions and product distributions. Successful use of ionic liquids in radiation-filled environments, where their safety advantages could be significant, requires an understanding of ionic liquid radiation chemistry. For example, characterizing the primary steps of IL radiolysis will reveal radiolytic degradation pathways and suggest ways to prevent them or mitigate their effects on the properties of the material. An understanding of ionic liquid radiation chemistry will also facilitate pulse radiolysis studies of general chemical reactivity in ILs, which will aid in the development of applications listed above. Very early in our radiolysis studies it became evident that slow solvation dynamics of the excess electron in ILs (which vary over a wide viscosity range) increases the importance of pre-solvated electron reactivity and consequently alters product distributions. Parallel studies of IL solvation phenomena using coumarin-153 dynamic Stokes shifts and polarization anisotropy decay rates are done to compare with electron solvation studies and to evaluate

  2. Cluster-continuum quasichemical theory calculation of the lithium ion solvation in water, acetonitrile and dimethyl sulfoxide: an absolute single-ion solvation free energy scale.

    Science.gov (United States)

    Carvalho, Nathalia F; Pliego, Josefredo R

    2015-10-28

    Absolute single-ion solvation free energy is a very useful property for understanding solution phase chemistry. The real solvation free energy of an ion depends on its interaction with the solvent molecules and on the net potential inside the solute cavity. The tetraphenyl arsonium-tetraphenyl borate (TATB) assumption as well as the cluster-continuum quasichemical theory (CC-QCT) approach for Li(+) solvation allows access to a solvation scale excluding the net potential. We have determined this free energy scale investigating the solvation of the lithium ion in water (H2O), acetonitrile (CH3CN) and dimethyl sulfoxide (DMSO) solvents via the CC-QCT approach. Our calculations at the MP2 and MP4 levels with basis sets up to the QZVPP+diff quality, and including solvation of the clusters and solvent molecules by the dielectric continuum SMD method, predict the solvation free energy of Li(+) as -116.1, -120.6 and -123.6 kcal mol(-1) in H2O, CH3CN and DMSO solvents, respectively (1 mol L(-1) standard state). These values are compatible with the solvation free energy of the proton of -253.4, -253.2 and -261.1 kcal mol(-1) in H2O, CH3CN and DMSO solvents, respectively. Deviations from the experimental TATB scale are only 1.3 kcal mol(-1) in H2O and 1.8 kcal mol(-1) in DMSO solvents. However, in the case of CH3CN, the deviation reaches a value of 9.2 kcal mol(-1). The present study suggests that the experimental TATB scale is inconsistent for CH3CN. A total of 125 values of the solvation free energy of ions in these three solvents were obtained. These new data should be useful for the development of theoretical solvation models.

  3. Quantum mechanical calculation of aqueuous uranium complexes: carbonate, phosphate, organic and biomolecular species

    Directory of Open Access Journals (Sweden)

    Jha Prashant

    2009-08-01

    Full Text Available Abstract Background Quantum mechanical calculations were performed on a variety of uranium species representing U(VI, U(V, U(IV, U-carbonates, U-phosphates, U-oxalates, U-catecholates, U-phosphodiesters, U-phosphorylated N-acetyl-glucosamine (NAG, and U-2-Keto-3-doxyoctanoate (KDO with explicit solvation by H2O molecules. These models represent major U species in natural waters and complexes on bacterial surfaces. The model results are compared to observed EXAFS, IR, Raman and NMR spectra. Results Agreement between experiment and theory is acceptable in most cases, and the reasons for discrepancies are discussed. Calculated Gibbs free energies are used to constrain which configurations are most likely to be stable under circumneutral pH conditions. Reduction of U(VI to U(IV is examined for the U-carbonate and U-catechol complexes. Conclusion Results on the potential energy differences between U(V- and U(IV-carbonate complexes suggest that the cause of slower disproportionation in this system is electrostatic repulsion between UO2 [CO3]35- ions that must approach one another to form U(VI and U(IV rather than a change in thermodynamic stability. Calculations on U-catechol species are consistent with the observation that UO22+ can oxidize catechol and form quinone-like species. In addition, outer-sphere complexation is predicted to be the most stable for U-catechol interactions based on calculated energies and comparison to 13C NMR spectra. Outer-sphere complexes (i.e., ion pairs bridged by water molecules are predicted to be comparable in Gibbs free energy to inner-sphere complexes for a model carboxylic acid. Complexation of uranyl to phosphorus-containing groups in extracellular polymeric substances is predicted to favor phosphonate groups, such as that found in phosphorylated NAG, rather than phosphodiesters, such as those in nucleic acids.

  4. A Single Stereodynamic Center Modulates the Rate of Self-Assembly in a Biomolecular System.

    Science.gov (United States)

    Zhang, Yitao; Malamakal, Roy M; Chenoweth, David M

    2015-09-07

    Chirality is a property of asymmetry important to both physical and abstract systems. Understanding how molecular systems respond to perturbations in their chiral building blocks can provide insight into diverse areas such as biomolecular self-assembly, protein folding, drug design, materials, and catalysis. Despite the fundamental importance of stereochemical preorganization in nature and designed materials, the ramifications of replacing chiral centers with stereodynamic atomic mimics in the context of biomolecular systems is unknown. Herein, we demonstrate that replacement of a single amino acid stereocenter with a stereodynamic nitrogen atom has profound consequences on the self-assembly of a biomolecular system. Our results provide insight into how the fundamental biopolymers of life would behave if their chiral centers were not configurationally stable, highlighting the vital importance of stereochemistry as a pre-organizing element in biomolecular folding and assembly events. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Computational study of TNT synthesis in solvated nitration reaction systems

    Science.gov (United States)

    Liu, Min-Hsien; Cheng, Ken-Fa; Chen, Cheng; Hong, Yaw-Sun

    Mononitrotoluene (MNT) was incorporated into solvated reaction systems and was subjected to subsequent nitration (electrophilic and free radical substitution) to obtain corresponding dinitrotoluene (DNT) and trinitrotoluene (TNT) products. In the electrophilic nitration system, the energy barrier of the reaction to produce o,p-dinitrotoluene from p-nitrotoluene was found to decrease from 62.7 to 14.7 kJ/mol to 9.2 kJ/mol in solventless, hydrated, and methanol-solvated molecular reaction systems, respectively. Further nitration to produce TNT in related solventless and solvated systems also led to a stepwise decreasing trend in the required energy, from 297.6 to 118.6 kJ/mol to 42.8 kJ/mol. Comparative synthesis using ·NO2 as the nitrating reagent to obtain o,p-DNT or TNT in the hydrated system shows a lower reaction energy barrier than that of the same reaction in the solventless system.

  6. Comparison of solvation dynamics of electrons in four polyols

    Energy Technology Data Exchange (ETDEWEB)

    Lampre, I.; Pernot, P.; Bonin, J. [Laboratoire de Chimie Physique/ELYSE, Universite Paris-Sud 11, UMR 8000, Bat. 349, Orsay F-91405 (France); CNRS, Orsay F-91405 (France); Mostafavi, M. [Laboratoire de Chimie Physique/ELYSE, Universite Paris-Sud 11, UMR 8000, Bat. 349, Orsay F-91405 (France); CNRS, Orsay F-91405 (France)], E-mail: mehran.mostafavi@lcp.u-psud.fr

    2008-10-15

    Using pump-probe transient absorption spectroscopy, we studied the solvation dynamics of the electron in liquid polyalcohols: ethane-1,2-diol, propane-1,2-diol, propane-1,3-diol and propane-1,2,3-triol. Time-resolved absorption spectra ranging from 440 to 720 nm were measured. Our study shows that the excess electron in the diols presents an intense and wide absorption band in the visible and near-IR spectral domain at early time after two-photon ionization of the neat solvent. Then, for the first tens of picoseconds, the electron spectrum shifts toward the blue domain and its bandwidth decreases as the red part of the initial spectrum rapidly drops, while the blue part hardly evolves. In contrast, in the triol, the absorption spectrum of the electron is early situated in the visible range after the pump pulse and then solely evolves in the red part. The Bayesian data analysis of the observed picosecond solvation dynamics with different models is in favor of a heterogeneous continuous relaxation. That is corroborated by the analogy between the change in the absorption band with increasing time or decreasing temperature. That tends to indicate a similar organization disorder of the solvent. Moreover, the electron solvation dynamics is very fast in propane-1,2,3-triol despite its high viscosity and highlight the role of the OH-group in that process.

  7. Enthalpy-entropy compensation: the role of solvation.

    Science.gov (United States)

    Dragan, Anatoliy I; Read, Christopher M; Crane-Robinson, Colyn

    2017-05-01

    Structural modifications to interacting systems frequently lead to changes in both the enthalpy (heat) and entropy of the process that compensate each other, so that the Gibbs free energy is little changed: a major barrier to the development of lead compounds in drug discovery. The conventional explanation for such enthalpy-entropy compensation (EEC) is that tighter contacts lead to a more negative enthalpy but increased molecular constraints, i.e., a compensating conformational entropy reduction. Changes in solvation can also contribute to EEC but this contribution is infrequently discussed. We review long-established and recent cases of EEC and conclude that the large fluctuations in enthalpy and entropy observed are too great to be a result of only conformational changes and must result, to a considerable degree, from variations in the amounts of water immobilized or released on forming complexes. Two systems exhibiting EEC show a correlation between calorimetric entropies and local mobilities, interpreted to mean conformational control of the binding entropy/free energy. However, a substantial contribution from solvation gives the same effect, as a consequence of a structural link between the amount of bound water and the protein flexibility. Only by assuming substantial changes in solvation-an intrinsically compensatory process-can a more complete understanding of EEC be obtained. Faced with such large, and compensating, changes in the enthalpies and entropies of binding, the best approach to engineering elevated affinities must be through the addition of ionic links, as they generate increased entropy without affecting the enthalpy.

  8. Accurate estimation of solvation free energy using polynomial fitting techniques.

    Science.gov (United States)

    Shyu, Conrad; Ytreberg, F Marty

    2011-01-15

    This report details an approach to improve the accuracy of free energy difference estimates using thermodynamic integration data (slope of the free energy with respect to the switching variable λ) and its application to calculating solvation free energy. The central idea is to utilize polynomial fitting schemes to approximate the thermodynamic integration data to improve the accuracy of the free energy difference estimates. Previously, we introduced the use of polynomial regression technique to fit thermodynamic integration data (Shyu and Ytreberg, J Comput Chem, 2009, 30, 2297). In this report we introduce polynomial and spline interpolation techniques. Two systems with analytically solvable relative free energies are used to test the accuracy of the interpolation approach. We also use both interpolation and regression methods to determine a small molecule solvation free energy. Our simulations show that, using such polynomial techniques and nonequidistant λ values, the solvation free energy can be estimated with high accuracy without using soft-core scaling and separate simulations for Lennard-Jones and partial charges. The results from our study suggest that these polynomial techniques, especially with use of nonequidistant λ values, improve the accuracy for ΔF estimates without demanding additional simulations. We also provide general guidelines for use of polynomial fitting to estimate free energy. To allow researchers to immediately utilize these methods, free software and documentation is provided via http://www.phys.uidaho.edu/ytreberg/software. Copyright © 2010 Wiley Periodicals, Inc.

  9. Solvation and hydration characteristics of ibuprofen and acetylsalicylic acid.

    Science.gov (United States)

    Perlovich, German L; Kurkov, Sergey V; Kinchin, Andrey N; Bauer-Brandl, Annette

    2004-01-26

    Ibuprofen and acetylsalicylic acid were studied by thermoanalytical methods: sublimation calorimetry, solution calorimetry, and with respect to solubility. Upon measuring the temperature dependences of the saturated vapor pressure, enthalpies of sublimation, DeltaH(0) (sub), as well as the entropies of sublimation, DeltaS(0) (sub), and their respective relative fractions in the total process were calculated. The Gibbs energy of solvation in aliphatic alcohols as well as the enthalpic and entropic fractions thereof were also studied and compared with the respective properties of model substances and other nonsteroidal antiinflammatory drugs (benzoic acid, diflunisal, flurbiprofen, ketoprofen, and naproxen). In all cases, enthalpy was found to be the driving force of the solvation process. Correlations were derived between Gibbs energy of solvation in octanol, DeltaG(Oct) (solv), and the transfer Gibbs energy from water to octanol, DeltaG(0) (tr). Influence of mutual octanol and water solubilities on the driving force of partitioning is discussed. An enthalpy-entropy-compensation effect in octanol was observed, and consequences of deviation from the general trend are also discussed.

  10. A closure relation to molecular theory of solvation for macromolecules

    Science.gov (United States)

    Kobryn, Alexander E.

    We propose a closure to the integral equations of molecular theory of solvation, particularly suitable for polar and charged macromolecules in electrolyte solution. This includes such systems as oligomeric polyelectrolytes at a finite concentration in aqueous and various non-aqueous solutions, as well as drug-like compounds in solution. The new closure (KGK closure) imposes the mean spherical approximation (MSA) almost everywhere in the solvation shell but levels out the density distribution function to zero inside the repulsive core and in the spatial regions of strong density depletion emerging due to molecular associative interactions. We test the performance of the KGK closure coupled to the reference interaction site model (RISM) on the examples of LJ liquids, polar and nonpolar molecular solvents, including water, and aqueous solutions of simple ions, and use the KGK closure to obtain the solvation structure and thermodynamics of oligomeric polyelectrolytes and drug-like compounds at a finite concentration in electrolyte solution, for which no convergence is obtained with other closures. We further test the 3D-version of the KGK closure with 3D-RISM for molecular mixtures as well as oligomeric polyelectrolytes and drug-like molecules in electrolyte solutions. 11421 Saskatchewan Drive, Edmonton, Alberta, T6G 2M9, Canada.

  11. Hydroxide Solvation and Transport in Anion Exchange Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chen [Univ. of Chicago, IL (United States); Wuhan Univ. (China); Tse, Ying-Lung Steve [Univ. of Chicago, IL (United States); Lindberg, Gerrick E. [Northern Arizona Univ., Flagstaff, AZ (United States); Knight, Chris [Argonne National Lab. (ANL), Argonne, IL (United States); Voth, Gregory A. [Univ. of Chicago, IL (United States)

    2016-01-27

    Understanding hydroxide solvation and transport in anion exchange membranes (AEMs) can provide important insight into the design principles of these new membranes. To accurately model hydroxide solvation and transport, we developed a new multiscale reactive molecular dynamics model for hydroxide in aqueous solution, which was then subsequently modified for an AEM material. With this model, we investigated the hydroxide solvation structure and transport mechanism in the membrane. We found that a relatively even separation of the rigid side chains produces a continuous overlapping region for hydroxide transport that is made up of the first hydration shell of the tethered cationic groups. Our results show that hydroxide has a significant preference for this overlapping region, transporting through it and between the AEM side chains with substantial contributions from both vehicular (standard diffusion) and Grotthuss (proton hopping) mechanisms. Comparison of the AEM with common proton exchange membranes (PEMs) showed that the excess charge is less delocalized in the AEM than the PEMs, which is correlated with a higher free energy barrier for proton transfer reactions. The vehicular mechanism also contributes considerably more than the Grotthuss mechanism for hydroxide transport in the AEM, while our previous studies of PEM systems showed a larger contribution from the Grotthuss mechanism than the vehicular mechanism for proton transport. The activation energy barrier for hydroxide diffusion in the AEM is greater than that for proton diffusion in PEMs, implying a more significant enhancement of ion transport in the AEM at elevated temperatures.

  12. Solvation structure of the halides from x-ray absorption spectroscopy

    Science.gov (United States)

    Antalek, Matthew; Pace, Elisabetta; Hedman, Britt; Hodgson, Keith O.; Chillemi, Giovanni; Benfatto, Maurizio; Sarangi, Ritimukta

    2016-01-01

    Three-dimensional models for the aqueous solvation structures of chloride, bromide, and iodide are reported. K-edge extended X-ray absorption fine structure (EXAFS) and Minuit X-ray absorption near edge (MXAN) analyses found well-defined single shell solvation spheres for bromide and iodide. However, dissolved chloride proved structurally distinct, with two solvation shells needed to explain its strikingly different X-ray absorption near edge structure (XANES) spectrum. Final solvation models were as follows: iodide, 8 water molecules at 3.60 ± 0.13 Å and bromide, 8 water molecules at 3.40 ± 0.14 Å, while chloride solvation included 7 water molecules at 3.15 ± 0.10 Å, and a second shell of 7 water molecules at 4.14 ± 0.30 Å. Each of the three derived solvation shells is approximately uniformly disposed about the halides, with no global asymmetry. Time-dependent density functional theory calculations simulating the chloride XANES spectra following from alternative solvation spheres revealed surprising sensitivity of the electronic state to 6-, 7-, or 8-coordination, implying a strongly bounded phase space for the correct structure during an MXAN fit. MXAN analysis further showed that the asymmetric solvation predicted from molecular dynamics simulations using halide polarization can play no significant part in bulk solvation. Classical molecular dynamics used to explore chloride solvation found a 7-water solvation shell at 3.12 (−0.04/+0.3) Å, supporting the experimental result. These experiments provide the first fully three-dimensional structures presenting to atomic resolution the aqueous solvation spheres of the larger halide ions. PMID:27475372

  13. Competitive solvation of (bis)(trifluoromethanesulfonyl)imide anion by acetonitrile and water

    DEFF Research Database (Denmark)

    Chaban, Vitaly

    2014-01-01

    Competitive solvation of an ion by two or more solvents is one of the key phenomena determining the identity of our world. Solvation in polar solvents frequently originates from non-additive non-covalent interactions. Pre-parametrized potentials poorly capture these interactions, unless the force...... and temperature coupling. Using a competitive solvation of (bis)(trifluoromethanesulfonyl)imide anion in acetonitrile and water, the work demonstrates efficiency and robustness of PM7-MD. (C) 2014 Elsevier B.V. All rights reserved....

  14. Combinatorial Biomolecular Nanopatterning for High-Throughput Screening of Stem-Cell Behavior.

    Science.gov (United States)

    Amin, Yacoub Y I; Runager, Kasper; Simoes, Fabio; Celiz, Adam; Taresco, Vincenzo; Rossi, Roberto; Enghild, Jan J; Abildtrup, Lisbeth A; Kraft, David C E; Sutherland, Duncan S; Alexander, Morgan R; Foss, Morten; Ogaki, Ryosuke

    2016-02-17

    A novel combinatorial biomolecular nanopatterning method is reported, in which multiple biomolecular ligands can be patterned in multiple nanoscale dimensions on a single surface. The applicability of the combinatorial platform toward cell-biology applications is demonstrated by screening the adhesion behavior of a population of human dental pulp stem cell (hDPSC) on 64 combinations of nanopatterned extracellular matrix (ECM) proteins in parallel. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Mathematical model for biomolecular quantification using large-area surface-enhanced Raman spectroscopy mapping

    DEFF Research Database (Denmark)

    Palla, Mirkó; Bosco, Filippo; Yang, Jaeyoung

    2015-01-01

    ) intensity distributions of target molecules on receptor-functionalized nanopillar substrates for biomolecular quantification. We demonstrate that by utilizing only a small set of empirically determined parameters, our general theoretical framework agrees with the experimental data particularly well...... in the picomolar concentration regimes. This developed model may be generally used for biomolecular quantification using Raman mapping on SERS substrates with planar geometries, in which the hotspots are approximated as electromagnetic enhancement fields generated by closely spaced dimers. Lastly, we also show...

  16. Evaluating the solvation properties of functionalized ionic liquids with varied cation/anion composition using the solvation parameter model.

    Science.gov (United States)

    Twu, Pamela; Zhao, Qichao; Pitner, William R; Acree, William E; Baker, Gary A; Anderson, Jared L

    2011-08-05

    Ionic liquids (ILs) are promising gas chromatography (GC) stationary phases due to their high thermal stability, negligible vapor pressure, and ability to solvate a broad range of analytes. The tunability of ILs allows for structure modification in pursuit of enhanced separation selectivity and control of analyte elution order. In this study, the solvation parameter model is used to characterize the solvation interactions of fifteen ILs containing various cationic functional groups (i.e., dimethylamino, hydroxyl, and ether) and cation types paired with various counter anions, namely, tris(pentafluoroethyl)trifluorophosphate (FAP(-)), bis[(trifluoromethyl)sulfonyl]imide (NTf(2)(-)), thiocyanate (SCN(-)), tricyanomethide (C(CN)(3)(-)), tetracyanoborate (B(CN)(4)(-)), and bis[oxalate(2-)]borate (BOB(-)). The presence of functional groups affected the hydrogen bond basicity, hydrogen bond acidity, as well as dispersion interactions of the resulting ILs, while the change of cation type yielded modest influence on the dipolarity. The switch of counter anions in unfunctionalized ILs produced compounds with higher dipolarity and hydrogen bond basicity. The dipolarity and hydrogen bond basicity of ILs possessing cyano-containing anions appeared to be inversely proportional to the cyano content of the anion. The modification of IL structure resulted in a significant effect on the retention behavior as well as separation selectivity for many solutes, including reversed elution orders of some analytes. This study provides one of the most comprehensive examinations up-to-date on the relation between IL structure and the resulting solvation characteristics and gives tremendous insight into choosing suitable ILs as GC stationary phases for solute specific separations. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Excitation Frequencies of the Effects of Selective Drift of Solvated Cations in Moving Salts Solution

    Directory of Open Access Journals (Sweden)

    Shamanin Igor

    2017-01-01

    Full Text Available Interaction of external electric field with free and bound charges in the salt solution volume in polar dielectric fluid was considered and the equation describing ion oscillations relative to solvent molecules was obtained. Fundamental frequencies of the solvation shell relative to the ion in different approximations describing the system: ion - solvation shell were evaluated. The results of comparison with the experiment pointed out that the model, in which the solvated ion is considered as a spherical rotator formed by the solvent molecules layer bordering with the external solvation shell, is the most appropriate. It provides an opportunity of development of new technologies for extraction of rare earth elements.

  18. Lengthscale-Dependent Solvation and Density Fluctuations in n-Octane.

    Science.gov (United States)

    Wu, Eugene; Garde, Shekhar

    2015-07-23

    Much attention has been focused on the solvation and density fluctuations in water over the past decade. These studies have brought to light interesting physical features of solvation in condensed media, especially the dependence of solvation on the solute lengthscale, which may be general to many fluids. Here, we focus on the lengthscale-dependent solvation and density fluctuations in n-octane, a simple organic liquid. Using extensive molecular simulations, we show a crossover in the solvation of solvophobic solutes with increasing size in n-octane, with the specifics of the crossover depending on the shape of the solute. Large lengthscale solvation, which is dominated by interface formation, emerges over subnanoscopic lengthscales. The crossover in n-octane occurs at smaller lengthscales than that in water. We connect the lengthscale of crossover to the range of attractive interactions in the fluid. The onset of the crossover is accompanied by the emergence of non-Gaussian tails in density fluctuations in solute shaped observation volumes. Simulations over a range of temperatures highlight a corresponding thermodynamic crossover in solvation. Qualitative similarities between lengthscale-dependent solvation in water, n-octane, and Lennard-Jones fluids highlight the generality of the underlying physics of solvation.

  19. Electron Solvation in Liquid Ammonia: Lithium, Sodium, Magnesium, and Calcium as Electron Sources.

    Science.gov (United States)

    Chaban, Vitaly V; Prezhdo, Oleg V

    2016-03-10

    A free electron in solution, known as a solvated electron, is the smallest possible anion. Alkali and alkaline earth atoms serve as electron donors in solvents that mediate outer-sphere electron transfer. We report herein ab initio molecular dynamics simulations of lithium, sodium, magnesium, and calcium in liquid ammonia at 250 K. By analyzing the electronic properties and the ionic and solvation structures and dynamics, we systematically characterize these metals as electron donors and ammonia molecules as electron acceptors. We show that the solvated metal strongly modifies the properties of its solvation shells and that the observed effect is metal-specific. Specifically, the radius and charge exhibit major impacts. The single solvated electron present in the alkali metal systems is distributed more uniformly among the solvent molecules of each metal's two solvation shells. In contrast, alkaline earth metals favor a less uniform distribution of the electron density. Alkali and alkaline earth atoms are coordinated by four and six NH3 molecules, respectively. The smaller atoms, Li and Mg, are stronger electron donors than Na and Ca. This result is surprising, as smaller atoms in a column of the periodic table have higher ionization potentials. However, it can be explained by stronger electron donor-acceptor interactions between the smaller atoms and the solvent molecules. The structure of the first solvation shell is sharpest for Mg, which has a large charge and a small radius. Solvation is weakest for Na, which has a small charge and a large radius. Weak solvation leads to rapid dynamics, as reflected in the diffusion coefficients of NH3 molecules of the first two solvation shells and the Na atom. The properties of the solvated electrons established in the present study are important for radiation chemistry, synthetic chemistry, condensed-matter charge transfer, and energy sources.

  20. Characterisation and evaluation of pharmaceutical solvates of Atorvastatin calcium by thermoanalytical and spectroscopic studies

    Directory of Open Access Journals (Sweden)

    Chadha Renu

    2012-10-01

    Full Text Available Abstract Background Atorvastatin calcium (ATC, an anti-lipid biopharmaceutical class II drug, is widely prescribed as a cholesterol-lowering agent and is presently the world’s best-selling medicine. A large number of crystalline forms of ATC have been published in patents. A variety of solid forms may give rise to different physical properties. Therefore, the discovery of new forms of this unusual molecule, ATC, may still provide an opportunity for further improvement of advantageous properties. Results In the present work, eight new solvates (Solvate I-VIII have been discovered by recrystallization method. Thermal behaviour of ATC and its solvates studied by DSC and TGA indicate similar pattern suggesting similar mode of entrapment of solvent molecules. The type of solvent present in the crystal lattice of the solvates is identified by GC-MS analysis and the stoichiometric ratio of the solvents is confirmed by 1HNMR. The high positive value of binding energy determined from thermochemical parameters indicates deep inclusion of the solvent molecules into the host cavity. The XRPD patterns point towards the differences in their crystallanity, however, after desolvation solvate II, III, IV, V and VIII transform to isostructral amorphous desolvated solvates. The order of crystallinity was confirmed by solution calorimetric technique as the enthalpy of solution is an indirect measure of lattice energy. All the solvates behaved endothermically following the order solvate-VIII (1-butanol solvate 13CP/MAS NMR spectral changes. Conclusions Aqueous solubility of solvate-VIII was found to be maximum, however, solvate-I and VIII showed better reduction in total cholesterol and triglyceride levels as compared to atorvastatin against triton-induced dyslipidemia.

  1. NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy.

    Science.gov (United States)

    Lee, Woonghee; Tonelli, Marco; Markley, John L

    2015-04-15

    SPARKY (Goddard and Kneller, SPARKY 3) remains the most popular software program for NMR data analysis, despite the fact that development of the package by its originators ceased in 2001. We have taken over the development of this package and describe NMRFAM-SPARKY, which implements new functions reflecting advances in the biomolecular NMR field. NMRFAM-SPARKY has been repackaged with current versions of Python and Tcl/Tk, which support new tools for NMR peak simulation and graphical assignment determination. These tools, along with chemical shift predictions from the PACSY database, greatly accelerate protein side chain assignments. NMRFAM-SPARKY supports automated data format interconversion for interfacing with a variety of web servers including, PECAN , PINE, TALOS-N, CS-Rosetta, SHIFTX2 and PONDEROSA-C/S. The software package, along with binary and source codes, if desired, can be downloaded freely from http://pine.nmrfam.wisc.edu/download_packages.html. Instruction manuals and video tutorials can be found at http://www.nmrfam.wisc.edu/nmrfam-sparky-distribution.htm. whlee@nmrfam.wisc.edu or markley@nmrfam.wisc.edu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

  2. Self-assembling biomolecular catalysts for hydrogen production.

    Science.gov (United States)

    Jordan, Paul C; Patterson, Dustin P; Saboda, Kendall N; Edwards, Ethan J; Miettinen, Heini M; Basu, Gautam; Thielges, Megan C; Douglas, Trevor

    2016-02-01

    The chemistry of highly evolved protein-based compartments has inspired the design of new catalytically active materials that self-assemble from biological components. A frontier of this biodesign is the potential to contribute new catalytic systems for the production of sustainable fuels, such as hydrogen. Here, we show the encapsulation and protection of an active hydrogen-producing and oxygen-tolerant [NiFe]-hydrogenase, sequestered within the capsid of the bacteriophage P22 through directed self-assembly. We co-opted Escherichia coli for biomolecular synthesis and assembly of this nanomaterial by expressing and maturing the EcHyd-1 hydrogenase prior to expression of the P22 coat protein, which subsequently self assembles. By probing the infrared spectroscopic signatures and catalytic activity of the engineered material, we demonstrate that the capsid provides stability and protection to the hydrogenase cargo. These results illustrate how combining biological function with directed supramolecular self-assembly can be used to create new materials for sustainable catalysis.

  3. The impact of the Biomolecular Era on breast cancer surgery.

    Science.gov (United States)

    McVeigh, T P; Boland, M R; Lowery, A J

    2017-06-01

    Surgery has always played a central role in the management of breast cancer, with local control via complete tumour resection long established as the cornerstone of effective breast cancer therapy. While extensive surgical resection in the form of the Halstead radical mastectomy dominated treatment up until at least the 1970s, the advent of adjuvant loco-regional and systemic therapies has resulted in a decrease in the magnitude of surgical intervention in recent decades. The Biomolecular or "-omics" era initiated with the discovery of the DNA double helix in 1953 and intensified by the completion of the human genome project in 2003 has seen an unprecedented expansion in our understanding of the molecular and genetic heterogeneity of cancer. This review will discuss how the clinical application of this knowledge in the direction of personalised risk assessment and breast cancer treatment has significant implications for modern surgical practice. Copyright © 2016 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  4. Label-free screening of bio-molecular interactions.

    Science.gov (United States)

    Cooper, Matthew A

    2003-11-01

    The majority of techniques currently employed to interrogate a biomolecular interaction require some type of radio- or enzymatic- or fluorescent-labelling to report the binding event. However, there is an increasing awareness of novel techniques that do not require labelling of the ligand or the receptor, and that allow virtually any complex to be screened with minimal assay development. This review focuses on three major label-free screening platforms: surface plasmon resonance biosensors, acoustic biosensors, and calorimetric biosensors. Scientists in both academia and industry are using biosensors in areas that encompass almost all areas drug discovery, diagnostics, and the life sciences. The capabilities and advantages of each technique are compared and key applications involving small molecules, proteins, oligonucleotides, bacteriophage, viruses, bacteria, and cells are reviewed. The role of the interface between the biosensor surface (in the case of SPR and acoustic biosensors) and the chemical or biological systems to be studied is also covered with attention to the covalent and non-covalent coupling chemistries commonly employed.

  5. A fast mollified impulse method for biomolecular atomistic simulations

    Energy Technology Data Exchange (ETDEWEB)

    Fath, L., E-mail: lukas.fath@kit.edu [Institute for App. and Num. Mathematics, Karlsruhe Institute of Technology (Germany); Hochbruck, M., E-mail: marlis.hochbruck@kit.edu [Institute for App. and Num. Mathematics, Karlsruhe Institute of Technology (Germany); Singh, C.V., E-mail: chandraveer.singh@utoronto.ca [Department of Materials Science & Engineering, University of Toronto (Canada)

    2017-03-15

    Classical integration methods for molecular dynamics are inherently limited due to resonance phenomena occurring at certain time-step sizes. The mollified impulse method can partially avoid this problem by using appropriate filters based on averaging or projection techniques. However, existing filters are computationally expensive and tedious in implementation since they require either analytical Hessians or they need to solve nonlinear systems from constraints. In this work we follow a different approach based on corotation for the construction of a new filter for (flexible) biomolecular simulations. The main advantages of the proposed filter are its excellent stability properties and ease of implementation in standard softwares without Hessians or solving constraint systems. By simulating multiple realistic examples such as peptide, protein, ice equilibrium and ice–ice friction, the new filter is shown to speed up the computations of long-range interactions by approximately 20%. The proposed filtered integrators allow step sizes as large as 10 fs while keeping the energy drift less than 1% on a 50 ps simulation.

  6. The fidelity of dynamic signaling by noisy biomolecular networks.

    Directory of Open Access Journals (Sweden)

    Clive G Bowsher

    Full Text Available Cells live in changing, dynamic environments. To understand cellular decision-making, we must therefore understand how fluctuating inputs are processed by noisy biomolecular networks. Here we present a general methodology for analyzing the fidelity with which different statistics of a fluctuating input are represented, or encoded, in the output of a signaling system over time. We identify two orthogonal sources of error that corrupt perfect representation of the signal: dynamical error, which occurs when the network responds on average to other features of the input trajectory as well as to the signal of interest, and mechanistic error, which occurs because biochemical reactions comprising the signaling mechanism are stochastic. Trade-offs between these two errors can determine the system's fidelity. By developing mathematical approaches to derive dynamics conditional on input trajectories we can show, for example, that increased biochemical noise (mechanistic error can improve fidelity and that both negative and positive feedback degrade fidelity, for standard models of genetic autoregulation. For a group of cells, the fidelity of the collective output exceeds that of an individual cell and negative feedback then typically becomes beneficial. We can also predict the dynamic signal for which a given system has highest fidelity and, conversely, how to modify the network design to maximize fidelity for a given dynamic signal. Our approach is general, has applications to both systems and synthetic biology, and will help underpin studies of cellular behavior in natural, dynamic environments.

  7. Stochastic Simulation of Biomolecular Networks in Dynamic Environments.

    Science.gov (United States)

    Voliotis, Margaritis; Thomas, Philipp; Grima, Ramon; Bowsher, Clive G

    2016-06-01

    Simulation of biomolecular networks is now indispensable for studying biological systems, from small reaction networks to large ensembles of cells. Here we present a novel approach for stochastic simulation of networks embedded in the dynamic environment of the cell and its surroundings. We thus sample trajectories of the stochastic process described by the chemical master equation with time-varying propensities. A comparative analysis shows that existing approaches can either fail dramatically, or else can impose impractical computational burdens due to numerical integration of reaction propensities, especially when cell ensembles are studied. Here we introduce the Extrande method which, given a simulated time course of dynamic network inputs, provides a conditionally exact and several orders-of-magnitude faster simulation solution. The new approach makes it feasible to demonstrate-using decision-making by a large population of quorum sensing bacteria-that robustness to fluctuations from upstream signaling places strong constraints on the design of networks determining cell fate. Our approach has the potential to significantly advance both understanding of molecular systems biology and design of synthetic circuits.

  8. Stochastic Simulation of Biomolecular Networks in Dynamic Environments.

    Directory of Open Access Journals (Sweden)

    Margaritis Voliotis

    2016-06-01

    Full Text Available Simulation of biomolecular networks is now indispensable for studying biological systems, from small reaction networks to large ensembles of cells. Here we present a novel approach for stochastic simulation of networks embedded in the dynamic environment of the cell and its surroundings. We thus sample trajectories of the stochastic process described by the chemical master equation with time-varying propensities. A comparative analysis shows that existing approaches can either fail dramatically, or else can impose impractical computational burdens due to numerical integration of reaction propensities, especially when cell ensembles are studied. Here we introduce the Extrande method which, given a simulated time course of dynamic network inputs, provides a conditionally exact and several orders-of-magnitude faster simulation solution. The new approach makes it feasible to demonstrate-using decision-making by a large population of quorum sensing bacteria-that robustness to fluctuations from upstream signaling places strong constraints on the design of networks determining cell fate. Our approach has the potential to significantly advance both understanding of molecular systems biology and design of synthetic circuits.

  9. Development of Implicit and Explicit Category Learning

    Science.gov (United States)

    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…

  10. Implicit and explicit instruction of spelling rules

    NARCIS (Netherlands)

    Kemper, M.J.; Verhoeven, L.T.W.; 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

  11. Implicit and Explicit Instruction of Spelling Rules

    Science.gov (United States)

    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…

  12. Signatures of Solvation Thermodynamics in Spectra of Intermolecular Vibrations

    Science.gov (United States)

    2017-01-01

    This study explores the thermodynamic and vibrational properties of water in the three-dimensional environment of solvated ions and small molecules using molecular simulations. The spectrum of intermolecular vibrations in liquid solvents provides detailed information on the shape of the local potential energy surface, which in turn determines local thermodynamic properties such as the entropy. Here, we extract this information using a spatially resolved extension of the two-phase thermodynamics method to estimate hydration water entropies based on the local vibrational density of states (3D-2PT). Combined with an analysis of solute–water and water–water interaction energies, this allows us to resolve local contributions to the solvation enthalpy, entropy, and free energy. We use this approach to study effects of ions on their surrounding water hydrogen bond network, its spectrum of intermolecular vibrations, and resulting thermodynamic properties. In the three-dimensional environment of polar and nonpolar functional groups of molecular solutes, we identify distinct hydration water species and classify them by their characteristic vibrational density of states and molecular entropies. In each case, we are able to assign variations in local hydration water entropies to specific changes in the spectrum of intermolecular vibrations. This provides an important link for the thermodynamic interpretation of vibrational spectra that are accessible to far-infrared absorption and Raman spectroscopy experiments. Our analysis provides unique microscopic details regarding the hydration of hydrophobic and hydrophilic functional groups, which enable us to identify interactions and molecular degrees of freedom that determine relevant contributions to the solvation entropy and consequently the free energy. PMID:28783431

  13. Signatures of Solvation Thermodynamics in Spectra of Intermolecular Vibrations.

    Science.gov (United States)

    Persson, Rasmus A X; Pattni, Viren; Singh, Anurag; Kast, Stefan M; Heyden, Matthias

    2017-09-12

    This study explores the thermodynamic and vibrational properties of water in the three-dimensional environment of solvated ions and small molecules using molecular simulations. The spectrum of intermolecular vibrations in liquid solvents provides detailed information on the shape of the local potential energy surface, which in turn determines local thermodynamic properties such as the entropy. Here, we extract this information using a spatially resolved extension of the two-phase thermodynamics method to estimate hydration water entropies based on the local vibrational density of states (3D-2PT). Combined with an analysis of solute-water and water-water interaction energies, this allows us to resolve local contributions to the solvation enthalpy, entropy, and free energy. We use this approach to study effects of ions on their surrounding water hydrogen bond network, its spectrum of intermolecular vibrations, and resulting thermodynamic properties. In the three-dimensional environment of polar and nonpolar functional groups of molecular solutes, we identify distinct hydration water species and classify them by their characteristic vibrational density of states and molecular entropies. In each case, we are able to assign variations in local hydration water entropies to specific changes in the spectrum of intermolecular vibrations. This provides an important link for the thermodynamic interpretation of vibrational spectra that are accessible to far-infrared absorption and Raman spectroscopy experiments. Our analysis provides unique microscopic details regarding the hydration of hydrophobic and hydrophilic functional groups, which enable us to identify interactions and molecular degrees of freedom that determine relevant contributions to the solvation entropy and consequently the free energy.

  14. Role of solvation structure in the shuttling of the hydrated excess ...

    Indian Academy of Sciences (India)

    The classic Marcus electron transfer reaction model demonstrated that a barrierless electron transfer reaction can occur when both the reactant and product have almost similar solvation environment. In our recently developed proton model, we have incorporated the pre-solvation concept and showed that it indeed ...

  15. Solvation and squeeze out of hexadecane on graphite

    Science.gov (United States)

    Gosvami, N. N.; Sinha, S. K.; Hofbauer, W.; O'Shea, S. J.

    2007-06-01

    We have performed simultaneous force and conductivity measurement of hexadecane liquid confined between a conducting atomic force microscope tip and a graphite surface. Both the current and the force data reveal discrete solvation layering of the hexadecane near the surface. We typically observe that the current does not vary with load in a simple way as the layer closest to the surface is compressed, but increases markedly prior to the expulsion of material from the tip-sample gap. We infer that even for a nanoscale asperity there is conformation change of the confined hexadecane under the tip apex prior to squeeze out of the molecules.

  16. Translational versus rotational energy flow in water solvation dynamics

    Science.gov (United States)

    Rey, Rossend; Hynes, James T.

    2017-09-01

    Early molecular dynamics simulations discovered an important asymmetry in the speed of water solvation dynamics for charge extinction and charge creation for an immersed solute, a feature representing a first demonstration of the breakdown of linear response theory. The molecular level mechanism of this asymmetry is examined here via a novel energy flux theoretical approach coupled to geometric probes. The results identify the effect as arising from the translational motions of the solute-hydrating water molecules rather than their rotational/librational motions, even though the latter are more rapid and dominate the energy flow.

  17. Solvation dynamics in water confined within layered manganese dioxide

    Science.gov (United States)

    Remsing, Richard C.; Klein, Michael L.

    2017-09-01

    The confined environment presented by layered transition metal oxides is conducive to a variety of chemical reactions. Despite intense interest in these materials, little is known regarding the microscopic details relevant to their catalytic activity. We characterize aspects of the dynamics governing a redox reaction in the interlayer environment between manganese dioxide sheets. The nonequilibrium solvation dynamics surrounding charge transfer between an ion and the surface are highly non-linear and exhibit long-time relaxation that is governed by collective dynamics. These dynamics are rationalized in terms of structural rearrangements, allowing connections to be made to more complex reactions in these materials.

  18. Moving solvated electrons with light: nonadiabatic mixed quantum/classical molecular dynamics simulations of the relocalization of photoexcited solvated electrons in tetrahydrofuran (THF).

    Science.gov (United States)

    Bedard-Hearn, Michael J; Larsen, Ross E; Schwartz, Benjamin J

    2006-11-21

    Motivated by recent ultrafast spectroscopic experiments [Martini et al., Science 293, 462 (2001)], which suggest that photoexcited solvated electrons in tetrahydrofuran (THF) can relocalize (that is, return to equilibrium in solvent cavities far from where they started), we performed a series of nonequilibrium, nonadiabatic, mixed quantum/classical molecular dynamics simulations that mimic one-photon excitation of the THF-solvated electron. We find that as photoexcited THF-solvated electrons relax to their ground states either by continuous mixing from the excited state or via nonadiabatic transitions, approximately 30% of them relocalize into cavities that can be over 1 nm away from where they originated, in close agreement with the experiments. A detailed investigation shows that the ability of excited THF-solvated electrons to undergo photoinduced relocalization stems from the existence of preexisting cavity traps that are an intrinsic part of the structure of liquid THF. This explains why solvated electrons can undergo photoinduced relocalization in solvents like THF but not in solvents like water, which lack the preexisting traps necessary to stabilize the excited electron in other places in the fluid. We also find that even when they do not ultimately relocalize, photoexcited solvated electrons in THF temporarily visit other sites in the fluid, explaining why the photoexcitation of THF-solvated electrons is so efficient at promoting recombination with nearby scavengers. Overall, our study shows that the defining characteristic of a liquid that permits the photoassisted relocalization of solvated electrons is the existence of nascent cavities that are attractive to an excess electron; we propose that other such liquids can be found from classical computer simulations or neutron diffraction experiments.

  19. Effect of Hydrofluoroether Cosolvent Addition on Li Solvation in Acetonitrile-Based Solvate Electrolytes and Its Influence on S Reduction in a Li-S Battery.

    Science.gov (United States)

    See, Kimberly A; Wu, Heng-Liang; Lau, Kah Chun; Shin, Minjeong; Cheng, Lei; Balasubramanian, Mahalingam; Gallagher, Kevin G; Curtiss, Larry A; Gewirth, Andrew A

    2016-12-21

    Li-S batteries are a promising next-generation battery technology. Due to the formation of soluble polysulfides during cell operation, the electrolyte composition of the cell plays an active role in directing the formation and speciation of the soluble lithium polysulfides. Recently, new classes of electrolytes termed "solvates" that contain stoichiometric quantities of salt and solvent and form a liquid at room temperature have been explored due to their sparingly solvating properties with respect to polysulfides. The viscosity of the solvate electrolytes is understandably high limiting their viability; however, hydrofluoroether cosolvents, thought to be inert to the solvate structure itself, can be introduced to reduce viscosity and enhance diffusion. Nazar and co-workers previously reported that addition of 1,1,2,2-tetrafluoroethyl 2,2,3,3-tetrafluoropropyl ether (TTE) to the LiTFSI in acetonitrile solvate, (MeCN)2-LiTFSI, results in enhanced capacity retention compared to the neat solvate. Here, we evaluate the effect of TTE addition on both the electrochemical behavior of the Li-S cell and the solvation structure of the (MeCN)2-LiTFSI electrolyte. Contrary to previous suggestions, Raman and NMR spectroscopy coupled with ab initio molecular dynamics simulations show that TTE coordinates to Li(+) at the expense of MeCN coordination, thereby producing a higher content of free MeCN, a good polysulfide solvent, in the electrolyte. The electrolytes containing a higher free MeCN content facilitate faster polysulfide formation kinetics during the electrochemical reduction of S in a Li-S cell likely as a result of the solvation power of the free MeCN.

  20. Binding energies, lifetimes and implications of bulk and interface solvated electrons in water.

    Science.gov (United States)

    Siefermann, Katrin R; Liu, Yaxing; Lugovoy, Evgeny; Link, Oliver; Faubel, Manfred; Buck, Udo; Winter, Bernd; Abel, Bernd

    2010-04-01

    Solvated electrons in liquid water are one of the seemingly simplest, but most important, transients in chemistry and biology, but they have resisted disclosing important information about their energetics, binding motifs and dynamics. Here we report the first ultrafast liquid-jet photoelectron spectroscopy measurements of solvated electrons in liquid water. The results prove unequivocally the existence of solvated electrons bound at the water surface and of solvated electrons in the bulk solution, with vertical binding energies of 1.6 eV and 3.3 eV, respectively, and with lifetimes longer than 100 ps. The unexpectedly long lifetime of solvated electrons bound at the water surface is attributed to a free-energy barrier that separates surface and interior states. Beyond constituting important energetic and kinetic benchmark and reference data, the results also help to understand the mechanisms of a number of very efficient electron-transfer processes in nature.

  1. Mini-grand canonical ensemble: Chemical potential in the solvation shell

    Science.gov (United States)

    Dixit, Purushottam D.; Bansal, Artee; Chapman, Walter G.; Asthagiri, Dilip

    2017-10-01

    Quantifying the statistics of occupancy of solvent molecules in the vicinity of solutes is central to our understanding of solvation phenomena. Number fluctuations in small solvation shells around solutes cannot be described within the macroscopic grand canonical framework using a single chemical potential that represents the solvent bath. In this communication, we hypothesize that molecular-sized observation volumes such as solvation shells are best described by coupling the solvation shell with a mixture of particle baths each with its own chemical potential. We confirm our hypotheses by studying the enhanced fluctuations in the occupancy statistics of hard sphere solvent particles around a distinguished hard sphere solute particle. Connections with established theories of solvation are also discussed.

  2. Liquid Atomic Force Microscopy: Solvation Forces, Molecular Order, and Squeeze-Out

    Science.gov (United States)

    O'Shea, Sean J.; Gosvami, Nitya N.; Lim, Leonard T. W.; Hofbauer, Wulf

    2010-08-01

    We review the use of atomic force microscopy (AFM) in liquids to measure oscillatory solvation forces. We find solvation layering can occur for all the liquids studied (linear and branched alkanes) but marked variations in the force and dissipation may arise dependent on: a) the temperature, b) the tip shape/radius of curvature, and c) the degree of molecular branching. Several findings (e.g., the strong temperature dependence in measured solvation forces, solvation oscillations using branched molecules) differ from those observed using the Surface Force Apparatus, because of the nanoscale area probed by AFM. Conduction AFM is used to explore how liquid is squeezed out of the tip-sample gap, and enables the change in contact area of the tip-sample junction to be monitored and compared to mechanical models. We find elastic models provide a good description of the deformation of ordered, solid-like solvation layers but not disordered, liquid-like layers.

  3. Evaluating the Effectiveness of Explicit Instruction on Implicit and Explicit L2 Knowledge

    Science.gov (United States)

    Akakura, Motoko

    2012-01-01

    This study examined the effectiveness of explicit instruction on second language (L2) learners' implicit and explicit knowledge of English. Explicit instruction on the generic and non-generic use of English articles was delivered by CALL activities. Four tasks assessed acquisition: elicited imitation, oral production, grammaticality judgement, and…

  4. Development of an informatics infrastructure for data exchange of biomolecular simulations: Architecture, data models and ontology.

    Science.gov (United States)

    Thibault, J C; Roe, D R; Eilbeck, K; Cheatham, T E; Facelli, J C

    2015-01-01

    Biomolecular simulations aim to simulate structure, dynamics, interactions, and energetics of complex biomolecular systems. With the recent advances in hardware, it is now possible to use more complex and accurate models, but also reach time scales that are biologically significant. Molecular simulations have become a standard tool for toxicology and pharmacology research, but organizing and sharing data - both within the same organization and among different ones - remains a substantial challenge. In this paper we review our recent work leading to the development of a comprehensive informatics infrastructure to facilitate the organization and exchange of biomolecular simulations data. Our efforts include the design of data models and dictionary tools that allow the standardization of the metadata used to describe the biomedical simulations, the development of a thesaurus and ontology for computational reasoning when searching for biomolecular simulations in distributed environments, and the development of systems based on these models to manage and share the data at a large scale (iBIOMES), and within smaller groups of researchers at laboratory scale (iBIOMES Lite), that take advantage of the standardization of the meta data used to describe biomolecular simulations.

  5. Evolution of biomolecular loadings along a major river system

    Science.gov (United States)

    Freymond, Chantal V.; Kündig, Nicole; Stark, Courcelle; Peterse, Francien; Buggle, Björn; Lupker, Maarten; Plötze, Michael; Blattmann, Thomas M.; Filip, Florin; Giosan, Liviu; Eglinton, Timothy I.

    2018-02-01

    Understanding the transport history and fate of organic carbon (OC) within river systems is crucial in order to constrain the dynamics and significance of land-ocean interactions as a component of the global carbon cycle. Fluvial export and burial of terrestrial OC in marine sediments influences atmospheric CO2 over a range of timescales, while river-dominated sedimentary sequences can provide valuable archives of paleoenvironmental information. While there is abundant evidence that the association of organic matter (OM) with minerals exerts an important influence on its stability as well as hydrodynamic behavior in aquatic systems, there is a paucity of information on where such associations form and how they evolve during fluvial transport. Here, we track total organic carbon (TOC) and terrestrial biomarker concentrations (plant wax-derived long-chain fatty acids (FA), branched glycerol dialkyl glycerol tetraethers (brGDGTs) and lignin-derived phenols) in sediments collected along the entire course of the Danube River system in the context of sedimentological parameters. Mineral-specific surface area-normalized biomarker and TOC concentrations show a systematic decrease from the upper to the lower Danube basin. Changes in OM loading of the available mineral phase correspond to a net decrease of 70-80% of different biomolecular components. Ranges for biomarker loadings on Danube River sediments, corresponding to 0.4-1.5 μgFA/m2 for long-chain (n-C24-32) fatty acids and 17-71 ngbrGDGT/m2 for brGDGTs, are proposed as a benchmark for comparison with other systems. We propose that normalizing TOC as well as biomarker concentrations to mineral surface area provides valuable quantitative constraints on OM dynamics and organo-mineral interactions during fluvial transport from terrigenous source to oceanic sink.

  6. Tuning structure and mobility of solvation shells surrounding tracer additives.

    Science.gov (United States)

    Carmer, James; Jain, Avni; Bollinger, Jonathan A; van Swol, Frank; Truskett, Thomas M

    2015-03-28

    Molecular dynamics simulations and a stochastic Fokker-Planck equation based approach are used to illuminate how position-dependent solvent mobility near one or more tracer particle(s) is affected when tracer-solvent interactions are rationally modified to affect corresponding solvation structure. For tracers in a dense hard-sphere fluid, we compare two types of tracer-solvent interactions: (1) a hard-sphere-like interaction, and (2) a soft repulsion extending beyond the hard core designed via statistical mechanical theory to enhance tracer mobility at infinite dilution by suppressing coordination-shell structure [Carmer et al., Soft Matter 8, 4083-4089 (2012)]. For the latter case, we show that the mobility of surrounding solvent particles is also increased by addition of the soft repulsive interaction, which helps to rationalize the mechanism underlying the tracer's enhanced diffusivity. However, if multiple tracer surfaces are in closer proximity (as at higher tracer concentrations), similar interactions that disrupt local solvation structure instead suppress the position-dependent solvent dynamics.

  7. Rotational spectrum of cyanoacetylene solvated with helium atoms.

    Science.gov (United States)

    Topic, W; Jäger, W; Blinov, N; Roy, P-N; Botti, M; Moroni, S

    2006-10-14

    The high resolution microwave spectra of He(N)-HCCCN clusters were studied in the size ranges of 1-18 and 25-31. In the absence of an accompanying infrared study, rotational excitation energies were computed by the reptation quantum Monte Carlo method and used to facilitate the search and assignment of R(0) transitions from N > 6, as well as R(1) transitions with N > 1. The assignments in the range of 25-31 are accurate to +/-2 cluster size units, with an essentially certain relative ordering. The rotational transition frequencies decrease with N = 1-6 and then show oscillatory behavior for larger cluster sizes, which is now recognized to be a manifestation of the onset and microscopic evolution of superfluidity. For cluster sizes beyond completion of the first solvation shell the rotational frequencies increase significantly above the large-droplet limit. This behavior, common to other linear molecules whose interaction with He features a strong nearly equatorial minimum, is analyzed using path integral Monte Carlo simulations. The He density in the incipient second solvation shell is shown to open a new channel for long permutation cycles, thus increasing the decoupling of the quantum solvent from the rotation of the dopant molecule.

  8. Explicit free‐floating beam element

    DEFF Research Database (Denmark)

    Nielsen, Martin Bjerre; Krenk, Steen

    2014-01-01

    A two‐node free‐floating beam element capable of undergoing arbitrary large displacements and finite rotations is presented in explicit form. The configuration of the beam in three‐dimensional space is represented by the global components of the position of the beam nodes and an associated set of...... interpolation of kinematic variables, resulting in a locking‐free formulation in terms of three explicit matrices. A set of classic benchmark examples illustrates excellent performance of the explicit beam element. Copyright © 2014 John Wiley & Sons, Ltd....

  9. Nonadiabatic dynamics of photoinduced proton-coupled electron transfer: comparison of explicit and implicit solvent simulations.

    Science.gov (United States)

    Auer, Benjamin; Soudackov, Alexander V; Hammes-Schiffer, Sharon

    2012-07-05

    Theoretical approaches for simulating the ultrafast dynamics of photoinduced proton-coupled electron transfer (PCET) reactions in solution are developed and applied to a series of model systems. These processes are simulated by propagating nonadiabatic surface hopping trajectories on electron-proton vibronic surfaces that depend on the solute and solvent nuclear coordinates. The PCET system is represented by a four-state empirical valence bond model, and the solvent is treated either as explicit solvent molecules or as a dielectric continuum, in which case the solvent dynamics is described in terms of two collective solvent coordinates corresponding to the energy gaps associated with electron and proton transfer. The explicit solvent simulations reveal two distinct solvent relaxation time scales, where the faster time scale relaxation corresponds to librational motions of solvent molecules in the first solvation shell, and the slower time scale relaxation corresponds to the bulk solvent dielectric response. The charge transfer dynamics is strongly coupled to both the fast and slow time scale solvent dynamics. The dynamical multistate continuum theory is extended to include the effects of two solvent relaxation time scales, and the resulting coupled generalized Langevin equations depend on parameters that can be extracted from equilibrium molecular dynamics simulations. The implicit and explicit solvent approaches lead to qualitatively similar charge transfer and solvent dynamics for model PCET systems, suggesting that the implicit solvent treatment captures the essential elements of the nonequilibrium solvent dynamics for many systems. A combination of implicit and explicit solvent approaches will enable the investigation of photoinduced PCET processes in a variety of condensed phase systems.

  10. Recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices.

    Science.gov (United States)

    Sasaki, Naoki

    2012-01-01

    AC electrokinetics is a generic term that refers to an induced motion of particles and fluids under nonuniform AC electric fields. The AC electric fields are formed by application of AC voltages to microelectrodes, which can be easily integrated into microfluidic devices by standard microfabrication techniques. Moreover, the magnitude of the motion is large enough to control the mass transfer on the devices. These advantages are attractive for biomolecular analysis on the microfluidic devices, in which the characteristics of small space and microfluidics have been mainly employed. In this review, I describe recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices. The applications include fluid pumping and mixing by AC electrokinetic flow, and manipulation of biomolecules such as DNA and proteins by various AC electrokinetic techniques. Future prospects for highly functional biomolecular analysis on microfluidic devices with the aid of AC electrokinetics are also discussed.

  11. Explicit equations of some elliptic modular surfaces

    NARCIS (Netherlands)

    Top, Jaap; Yui, Noriko

    2007-01-01

    We present explicit equations of semi-stable elliptic surfaces (i.e., having only type In singular fibers) which are associated to the torsion-free genus zero congruence subgroups of a modular group as previously classified.

  12. Explicit Instruction Elements in Core Reading Programs

    OpenAIRE

    Child, Angela R.

    2012-01-01

    Classroom teachers are provided instructional recommendations for teaching reading from their adopted core reading programs (CRPs). Explicit instruction elements or what is also called instructional moves, including direct explanation, modeling, guided practice, independent practice, discussion, feedback, and monitoring, were examined within CRP reading lessons. This study sought to answer the question: What elements of explicit instruction or instructional moves are included in the five most...

  13. Topology Optimization using an Explicit Interface Representation

    DEFF Research Database (Denmark)

    Christiansen, Asger Nyman; Nobel-Jørgensen, Morten; Bærentzen, J. Andreas

    Current methods for topology optimization primarily represent the interface between solid and void implicitly on fixed grids. In contrast, shape optimization methods represent the interface explicitly, but do not allow for any topological changes to the structure. Using an explicit interface repr...... seconds on an ordinary laptop utilizing a single thread. In addition, a coarse solution to the same problem has been obtained in approximately 10 seconds....

  14. Engineering intracellular active transport systems as in vivo biomolecular tools.

    Energy Technology Data Exchange (ETDEWEB)

    Bachand, George David; Carroll-Portillo, Amanda

    2006-11-01

    Active transport systems provide essential functions in terms of cell physiology and metastasis. These systems, however, are also co-opted by invading viruses, enabling directed transport of the virus to and from the cell's nucleus (i.e., the site of virus replication). Based on this concept, fundamentally new approaches for interrogating and manipulating the inner workings of living cells may be achievable by co-opting Nature's active transport systems as an in vivo biomolecular tool. The overall goal of this project was to investigate the ability to engineer kinesin-based transport systems for in vivo applications, specifically the collection of effector proteins (e.g., transcriptional regulators) within single cells. In the first part of this project, a chimeric fusion protein consisting of kinesin and a single chain variable fragment (scFv) of an antibody was successfully produced through a recombinant expression system. The kinesin-scFv retained both catalytic and antigenic functionality, enabling selective capture and transport of target antigens. The incorporation of a rabbit IgG-specific scFv into the kinesin established a generalized system for functionalizing kinesin with a wide range of target-selective antibodies raised in rabbits. The second objective was to develop methods of isolating the intact microtubule network from live cells as a platform for evaluating kinesin-based transport within the cytoskeletal architecture of a cell. Successful isolation of intact microtubule networks from two distinct cell types was demonstrated using glutaraldehyde and methanol fixation methods. This work provides a platform for inferring the ability of kinesin-scFv to function in vivo, and may also serve as a three-dimensional scaffold for evaluating and exploiting kinesin-based transport for nanotechnological applications. Overall, the technology developed in this project represents a first-step in engineering active transport system for in vivo

  15. Reproducing the Ensemble Average Polar Solvation Energy of a Protein from a Single Structure: Gaussian-Based Smooth Dielectric Function for Macromolecular Modeling.

    Science.gov (United States)

    Chakravorty, Arghya; Jia, Zhe; Li, Lin; Zhao, Shan; Alexov, Emil

    2018-01-19

    Typically, the ensemble average polar component of solvation energy (∆G_polar^solv) of a macromolecule is computed using molecular dynamics (MD) or Monte Carlo (MC) simulations to generate conformational ensemble and then single/rigid conformation solvation energy calculation is performed on each of snapshots. The primary objective of this work is to demonstrate that Poisson-Boltzmann (PB) based approach using a Gaussian-based smooth dielectric function for macromolecular modeling previously developed by us (Li et al. J Chem Theory Comput 2013, 9 (4), 2126-2136) can reproduce the ensemble average (∆G_polar^solv) of a protein from a single structure. We show that the Gaussian-based dielectric model reproduces the ensemble average ∆G_polar^solv (〈∆G_polar^solv 〉) from an energy minimized structure regardless minimization environment (structure minimized in vacuo, implicit or explicit waters or crystal structure). The best case, however, is when it is paired with in vacuo minimized structure. In contrast, the traditional 2-dielectric model is successful in reproducing the ensemble average (∆G_polar^solv) only if the crystal structure or a structure minimized in solvent is used, the best being the case of implicit solvent minimized structure. Moreover, the traditional 2-dielectric model tends to underestimate the ensemble average 〈∆G_polar^solv 〉 even when the internal dielectric constant of macromolecule takes the lowest physically reasonable value of 1. Our observations from this work reflect how the ability to appropriately mimic the motion of residues, especially the salt-bridges residues, influences a dielectric model's ability to reproduce the ensemble average value of polar solvation free energy from a single structure.

  16. Selective nonspecific solvation under dielectric saturation and fluorescence spectra of dye solutions in binary solvents.

    Science.gov (United States)

    Bakhshiev, N G; Kiselev, M B

    1991-09-01

    The influence of selective nonspecific solvation on the fluorescence spectra of three substitutedN-methylphthalimides in a binary solvent system consisting of a nonpolar (n-heptane) and a polar (pyridine) component has been studied under conditions close to dielectric saturation. The substantially nonlinearity of the effect is confirmation that the spectral shifts of fluorescence bands depend on the number of polar solvent molecules involved in solvating the dye molecule. The measured fluorescence spectral shifts determined by substituting one nonpolar solvent molecula with a polar one in the proximity of the dye molecule agree quantitatively with the forecasts of the previously proposed semiempirical theory which describes this nonlinear solvation phenomenon.

  17. An ESR Saturation Treatment for Solvated-Electron Systems

    Science.gov (United States)

    Hiromitsu, Ichiro; Hase, Hirotomo; Higashimura, Takenobu

    1985-06-01

    ESR saturation measurements of solvated electrons (esol-) in alkaline ices were carried out at 73 K and 4 K. When there was no cross-relaxation for esol-, the observed line widths of esol- did not agree with those calculated by Zhidkov’s treatment. The larger spin-packet width found at 73 K than that at 4 K was interpreted in terms of spectral diffusion. When cross-relaxation occurred between esol- and neighbouring radicals, the line widths of esol- were interpreted as being due to both the spectral diffusion and the cross-relaxation. A more comprehensive treatment including a cross-relaxation time is presented; this treatment succeeds in fitting the observed line widths to the theoretical ones.

  18. Improved Dielectric Solvation Model for Electronic Structure Calculations

    Energy Technology Data Exchange (ETDEWEB)

    Chipman, Daniel M. [Univ. of Notre Dame, IN (United States)

    2015-12-16

    This project was originally funded for the three year period from 09/01/2009 to 08/31/2012. Subsequently a No-Cost Extension was approved for a revised end date of 11/30/2013. The primary goals of the project were to develop continuum solvation models for nondielectric short-range interactions between solvent and solute that arise from dispersion, exchange, and hydrogen bonding. These goals were accomplished and are reported in the five peer-reviewed journal publications listed in the bibliography below. The secondary goals of the project included derivation of analytic gradients for the models, improvement of the cavity integration scheme, application of the models to the core-level spectroscopy of water, and several other miscellaneous items. These goals were not accomplished because they depended on completion of the primary goals, after which there was a lack of time for any additional effort.

  19. Solvation Free Energies of Alanine Peptides: The Effect of Flexibility

    Energy Technology Data Exchange (ETDEWEB)

    Kokubo, Hironori; Harris, Robert C.; Asthagiri, Dilip; Pettitt, Bernard M.

    2013-12-03

    The electrostatic (?Gel), cavity-formation (?Gvdw), and total (?G) solvation free energies for 10 alanine peptides ranging in length (n) from 1 to 10 monomers were calculated. The free energies were computed both with xed, extended conformations of the peptides and again for some of the peptides without constraints. The solvation free energies, ?Gel, ?Gvdw, and ?G, were found to be linear in n, with the slopes of the best-fit lines being gamma_el, gamma_vdw, and gamma, respectively. Both gamma_el and gamma were negative for fixed and flexible peptides, and gamma_vdw was negative for fixed peptides. That gamma_vdw was negative was surprising, as experimental data on alkanes, theoretical models, and MD computations on small molecules and model systems generally suggest that gamma_vdw should be positive. A negative gamma_vdw seemingly contradicts the notion that ?Gvdw drives the initial collapse of the protein when it folds by favoring conformations with small surface areas, but when we computed ?Gvdw for the flexible peptides, thereby allowing the peptides to assume natural ensembles of more compact conformations, gamma-vdw was positive. Because most proteins do not assume extended conformations, a ?Gvdw that increases with increasing surface area may be typical for globular proteins. An alternative hypothesis is that the collapse is driven by intramolecular interactions. We show that the intramolecular van der Waal's interaction energy is more favorable for the flexible than for the extended peptides, seemingly favoring this hypothesis, but the large fluctuations in this energy may make attributing the collapse of the peptide to this intramolecular energy difficult.

  20. Effect of the Hydrofluoroether Cosolvent Structure in Acetonitrile-Based Solvate Electrolytes on the Li+ Solvation Structure and Li-S Battery Performance.

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Minjeong; Wu, Heng-Liang; Narayanan, Badri; See, Kimberly A.; Assary, Rajeev S.; Zhu, Lingyang; Haasch, Richard T.; Zhang, Shuo; Zhang, Zhengcheng; Curtiss, Larry A.; Gewirth, Andrew A.

    2017-11-15

    We evaluate hydrofluoroether (HFE) cosolvents with varying degrees of fluorination in the acetonitrile-based solvate electrolyte to determine the effect of the HFE structure on the electrochemical performance of the Li-S battery. Solvates or sparingly solvating electrolytes are an interesting electrolyte choice for the Li-S battery due to their low polysulfide solubility. The solvate electrolyte with a stoichiometric ratio of LiTFSI salt in acetonitrile, (MeCN)(2)-LiTFSI, exhibits limited polysulfide solubility due to the high concentration of LiTFSI. We demonstrate that the addition of highly fluorinated HFEs to the solvate yields better capacity retention compared to that of less fluorinated HFE cosolvents. Raman and NMR spectroscopy coupled with ab initio molecular dynamics simulations show that HFEs exhibiting a higher degree of fluorination coordinate to Li+ at the expense of MeCN coordination, resulting in higher free MeCN content in solution. However, the polysulfide solubility remains low, and no crossover of polysulfides from the S cathode to the Li anode is observed.

  1. The interaction of implicit learning, explicit hypothesis testing learning and implicit-to-explicit knowledge extraction.

    Science.gov (United States)

    Sun, Ron; Zhang, Xi; Slusarz, Paul; Mathews, Robert

    2007-01-01

    To further explore the interaction between the implicit and explicit learning processes in skill acquisition (which have been tackled before, e.g. in [Sun, R., Merrill, E., & Peterson, T. (2001). From implicit skill to explicit knowledge: A bottom-up model of skill learning. Cognitive Science, 25(2), 203-244; Sun, R., Slusarz, P., & Terry, C. (2005). The interaction of the explicit and the implicit in skill learning: A dual-process approach. Psychological Review, 112(1), 159-192]), this paper explores details of the interaction of different learning modes: implicit learning, explicit hypothesis testing learning, and implicit-to-explicit knowledge extraction. Contrary to the common tendency in the literature to study each type of learning in isolation, this paper highlights the interaction among them and various effects of the interaction on learning, including the synergy effect. This work advocates an integrated model of skill learning that takes into account both implicit and explicit learning processes; moreover, it also uniquely embodies a bottom-up (implicit-to-explicit) learning approach in addition to other types of learning. The paper shows that this model accounts for various effects in the human behavioural data from the psychological experiments with the process control task, in addition to accounting for other data in other psychological experiments (which has been reported elsewhere). The paper shows that to account for these effects, implicit learning, bottom-up implicit-to-explicit extraction and explicit hypothesis testing learning are all needed.

  2. Reference interaction site model with hydrophobicity induced density inhomogeneity: An analytical theory to compute solvation properties of large hydrophobic solutes in the mixture of polyatomic solvent molecules

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Siqin [The HKUST Shenzhen Research Institute, Shenzhen (China); Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong); Sheong, Fu Kit [Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong); Huang, Xuhui, E-mail: xuhuihuang@ust.hk [The HKUST Shenzhen Research Institute, Shenzhen (China); Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong); Division of Biomedical Engineering, Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong)

    2015-08-07

    Reference interaction site model (RISM) has recently become a popular approach in the study of thermodynamical and structural properties of the solvent around macromolecules. On the other hand, it was widely suggested that there exists water density depletion around large hydrophobic solutes (>1 nm), and this may pose a great challenge to the RISM theory. In this paper, we develop a new analytical theory, the Reference Interaction Site Model with Hydrophobicity induced density Inhomogeneity (RISM-HI), to compute solvent radial distribution function (RDF) around large hydrophobic solute in water as well as its mixture with other polyatomic organic solvents. To achieve this, we have explicitly considered the density inhomogeneity at the solute-solvent interface using the framework of the Yvon-Born-Green hierarchy, and the RISM theory is used to obtain the solute-solvent pair correlation. In order to efficiently solve the relevant equations while maintaining reasonable accuracy, we have also developed a new closure called the D2 closure. With this new theory, the solvent RDFs around a large hydrophobic particle in water and different water-acetonitrile mixtures could be computed, which agree well with the results of the molecular dynamics simulations. Furthermore, we show that our RISM-HI theory can also efficiently compute the solvation free energy of solute with a wide range of hydrophobicity in various water-acetonitrile solvent mixtures with a reasonable accuracy. We anticipate that our theory could be widely applied to compute the thermodynamic and structural properties for the solvation of hydrophobic solute.

  3. Accurate prediction of explicit solvent atom distribution in HIV-1 protease and F-ATP synthase by statistical theory of liquids

    Science.gov (United States)

    Sindhikara, Daniel; Yoshida, Norio; Hirata, Fumio

    2012-02-01

    We have created a simple algorithm for automatically predicting the explicit solvent atom distribution of biomolecules. The explicit distribution is coerced from the 3D continuous distribution resulting from a 3D-RISM calculation. This procedure predicts optimal location of solvent molecules and ions given a rigid biomolecular structure. We show examples of predicting water molecules near KNI-275 bound form of HIV-1 protease and predicting both sodium ions and water molecules near the rotor ring of F-ATP synthase. Our results give excellent agreement with experimental structure with an average prediction error of 0.45-0.65 angstroms. Further, unlike experimental methods, this method does not suffer from the partial occupancy limit. Our method can be performed directly on 3D-RISM output within minutes. It is useful not only as a location predictor but also as a convenient method for generating initial structures for MD calculations.

  4. Student Learning about Biomolecular Self-Assembly Using Two Different External Representations

    Science.gov (United States)

    Host, Gunnar E.; Larsson, Caroline; Olson, Arthur; Tibell, Lena A. E.

    2013-01-01

    Self-assembly is the fundamental but counterintuitive principle that explains how ordered biomolecular complexes form spontaneously in the cell. This study investigated the impact of using two external representations of virus self-assembly, an interactive tangible three-dimensional model and a static two-dimensional image, on student learning…

  5. CytoCtrlAnalyser: a Cytoscape app for biomolecular network controllability analysis.

    Science.gov (United States)

    Wu, Lin; Min, Li; Wang, Jianxin; Wu, Fang-Xiang

    2017-11-23

    Studying the controllability of biomolecular networks can result in profound knowledge about molecular biological systems. However, there is no comprehensive and easy-to-use platform for analyzing controllability of biomolecular networks although various algorithms for analyzing complex network controllability have been proposed recently. In this application note, we develop the CytoCtrlAnalyser which is a Cytoscape app to provide a comprehensive platform for analyzing controllability of biomolecular networks. Nine algorithms have been integrated in CytoCtrlAnalyser. With network topologies and customized control settings imported into CytoCtrlAnalyser, users can identify the steering nodes which should be actuated by input control signals for achieving different control objectives as well as investigate the importance of nodes from different perspectives in the controllability of networks. CytoCtrlAnalyser offers a tool for many promising applications, such as identification of potential drug targets or biologically important nodes in biomolecular networks. Freely available for downloading at http://apps.cytoscape.org/apps/cytoctrlanalyser. faw341@mail.usask.ca. Supplementary data are available at Bioinformatics online.

  6. Optical Coherence Tomography and Biomolecular Imaging with Coherent Raman Scattering Microscopy

    DEFF Research Database (Denmark)

    Andersson-Engels, Stefan; Andersen, Peter E.

    2014-01-01

    The Special Section on Selected Topics in Biophotonics: Optical Coherence Tomography and Biomolecular Imaging with Coherent Raman Scattering Microscopy comprises two invited review papers and several contributed papers from the summer school Biophotonics ’13, as well as contributed papers within...

  7. The HADDOCK2.2 Web Server : User-Friendly Integrative Modeling of Biomolecular Complexes

    NARCIS (Netherlands)

    Van Zundert, G. C P; Rodrigues, J. P G L M; Trellet, M.; Schmitz, C.; Kastritis, P. L.; Karaca, E.; Melquiond, A. S J; Van Dijk, M.; De Vries, S. J.; Bonvin, A. M J J

    2016-01-01

    The prediction of the quaternary structure of biomolecular macromolecules is of paramount importance for fundamental understanding of cellular processes and drug design. In the era of integrative structural biology, one way of increasing the accuracy of modeling methods used to predict the structure

  8. Computer Programming and Biomolecular Structure Studies: A Step beyond Internet Bioinformatics

    Science.gov (United States)

    Likic, Vladimir A.

    2006-01-01

    This article describes the experience of teaching structural bioinformatics to third year undergraduate students in a subject titled "Biomolecular Structure and Bioinformatics." Students were introduced to computer programming and used this knowledge in a practical application as an alternative to the well established Internet bioinformatics…

  9. Global analysis of time-resolved fluorescence microspectroscopy and applications in biomolecular studies

    NARCIS (Netherlands)

    Laptenok, S.

    2009-01-01

    Understanding the properties of biomolecular networks is of central importance in life sciences. Optical microscopy has been very useful to determine the sub-cellular localisation of proteins but it cannot reveal whether proteins interact with one another. Micro-spectroscopic techniques (combining

  10. Conformation of bovine submaxillary mucin layers on hydrophobic surface as studied by biomolecular probes

    DEFF Research Database (Denmark)

    Pakkanen, Kirsi I.; Madsen, Jan Busk; Lee, Seunghwan

    2015-01-01

    non-linear responses with increasing surface concentration. The results from this study support the conventional amphiphilic, triblock model of BSM in the adsorption onto hydrophobic surface from aqueous solution.The biomolecular probe-based approaches employed in this study, however, provided further...

  11. DESTRUCTION OF HALOGENATED HYDROCARBONS WITH SOLVATED ELECTRONS IN THE PRESENCE OF WATER. (R826180)

    Science.gov (United States)

    Model halogenated aromatic and aliphatic hydrocarbons and halogenated phenols were dehalogenated in seconds by solvated electrons generated from sodium in both anhydrous liquid ammonia and ammonia/water solutions. The minimum sodium required to completely dehalogenate these mo...

  12. Entropic solvation force between surfaces modified by grafted chains: a density functional approach

    Directory of Open Access Journals (Sweden)

    O. Pizio

    2010-01-01

    Full Text Available The behavior of a hard sphere fluid in slit-like pores with walls modified by grafted chain molecules composed of hard sphere segments is studied using density functional theory. The chains are grafted to opposite walls via terminating segments forming pillars. The effects of confinement and of "chemical" modification of pore walls on the entropic solvation force are investigated in detail. We observe that in the absence of adsorbed fluid the solvation force is strongly repulsive for narrow pores and attractive for wide pores. In the presence of adsorbed fluid both parts of the curve of the solvation force may develop oscillatory behavior dependent on the density of pillars, the number of segments and adsorption conditions. Also, the size ratio between adsorbed fluid species and chain segments is of importance for the development of oscillations. The choice of these parameters is crucial for efficient manipulation of the solvation force as desired for pores of different width.

  13. Polar solvation dynamics of coumarin 153 by ultrafast time-resolved fluorescence

    Science.gov (United States)

    Eom, Intae; Joo, Taiha

    2009-12-01

    Polar solvation dynamics of coumarin 153 in acetonitrile, methanol, and butanol are investigated by dynamic Stokes shift function, S(t ). In small protic solvents, it is known that an initial ultrafast component below 50 fs constitutes more than half of the total solvation process. We use fluorescence up-conversion technique via two-photon absorption process, which can provide 40 fs time resolution for the whole emission wavelength range. Moreover, time-resolved fluorescence spectra are recorded directly without the spectral reconstruction. We observe a temporal oscillation in frequency of whole emission spectrum in the solvation curve. In the obtained S(t ), initial solvation time scale is 120 fs, invariant to solvents used in this experiment, although its amplitude varies in different solvents.

  14. Brain Networks of Explicit and Implicit Learning

    Science.gov (United States)

    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

  15. Effect of phosphatidylcholine on explicit memory.

    Science.gov (United States)

    Ladd, S L; Sommer, S A; LaBerge, S; Toscano, W

    1993-12-01

    Previous studies have not demonstrated a consistent relationship between precursors to acetylcholine (ACh) and memory function in normal human subjects. This experiment (N = 80, college students) employed a double-blind mixed design to test the effect of phosphatidylcholine (PCh) on explicit memory. Dose of placebo and PCh was compared at two levels (10 and 25 g) as was time of testing postingestion (60 and 90 min). With 25 g of PCh, which supplies 3.75 g of choline, significant improvement in explicit memory, as measured by a serial learning task, was observed at 90 min postingestion and slight improvement was observed at 60 min postigestion. Further analyses indicated that this improvement may have been due to the responses of slow learners. This is the first study to test the relationship between a single dose of PCh and explicit memory on normal human subjects.

  16. Implicit and explicit processes in social cognition

    DEFF Research Database (Denmark)

    Frith, Christopher; Frith, Uta

    2008-01-01

    In this review we consider research on social cognition in which implicit processes can be compared and contrasted with explicit, conscious processes. In each case, their function is distinct, sometimes complementary and sometimes oppositional. We argue that implicit processes in social interaction...... are automatic and are often opposed to conscious strategies. While we are aware of explicit processes in social interaction, we cannot always use them to override implicit processes. Many studies show that implicit processes facilitate the sharing of knowledge, feelings, and actions, and hence, perhaps...

  17. New explicit expressions for Dirac bilinears

    Science.gov (United States)

    Lorcé, Cédric

    2018-01-01

    We derive new explicit expressions for the Dirac bilinears based on a generic representation of the massive Dirac spinors with canonical polarization. These bilinears depend on a direction n in Minkowski space which specifies the form of dynamics. We argue that such a dependence is unavoidable in a relativistic theory with spin, since it originates from Wigner rotation effects. Contrary to most of the expressions found in the literature, ours are valid for all momenta and canonical polarizations of the spinors. As a byproduct, we also obtain a generic explicit expression for the covariant spin vector.

  18. Electromagnetic radiation under explicit symmetry breaking.

    Science.gov (United States)

    Sinha, Dhiraj; Amaratunga, Gehan A J

    2015-04-10

    We report our observation that radiation from a system of accelerating charges is possible only when there is explicit breaking of symmetry in the electric field in space within the spatial configuration of the radiating system. Under symmetry breaking, current within an enclosed area around the radiating structure is not conserved at a certain instant of time resulting in radiation in free space. Electromagnetic radiation from dielectric and piezoelectric material based resonators are discussed in this context. Finally, it is argued that symmetry of a resonator of any form can be explicitly broken to create a radiating antenna.

  19. Solvation thermodynamics and heat capacity of polar and charged solutes in water.

    Science.gov (United States)

    Sedlmeier, Felix; Netz, Roland R

    2013-03-21

    The solvation thermodynamics and in particular the solvation heat capacity of polar and charged solutes in water is studied using atomistic molecular dynamics simulations. As ionic solutes we consider a F(-) and a Na(+) ion, as an example for a polar molecule with vanishing net charge we take a SPC/E water molecule. The partial charges of all three solutes are varied in a wide range by a scaling factor. Using a recently introduced method for the accurate determination of the solvation free energy of polar solutes, we determine the free energy, entropy, enthalpy, and heat capacity of the three different solutes as a function of temperature and partial solute charge. We find that the sum of the solvation heat capacities of the Na(+) and F(-) ions is negative, in agreement with experimental observations, but our results uncover a pronounced difference in the heat capacity between positively and negatively charged groups. While the solvation heat capacity ΔC(p) stays positive and even increases slightly upon charging the Na(+) ion, it decreases upon charging the F(-) ion and becomes negative beyond an ion charge of q = -0.3e. On the other hand, the heat capacity of the overall charge-neutral polar solute derived from a SPC/E water molecule is positive for all charge scaling factors considered by us. This means that the heat capacity of a wide class of polar solutes with vanishing net charge is positive. The common ascription of negative heat capacities to polar chemical groups might arise from the neglect of non-additive interaction effects between polar and apolar groups. The reason behind this non-additivity is suggested to be related to the second solvation shell that significantly affects the solvation thermodynamics and due to its large spatial extent induces quite long-ranged interactions between solvated molecular parts and groups.

  20. Implementation and testing of stable, fast implicit solvation in molecular dynamics using the smooth-permittivity finite difference Poisson-Boltzmann method.

    Science.gov (United States)

    Prabhu, Ninad V; Zhu, Peijuan; Sharp, Kim A

    2004-12-01

    A fast stable finite difference Poisson-Boltzmann (FDPB) model for implicit solvation in molecular dynamics simulations was developed using the smooth permittivity FDPB method implemented in the OpenEye ZAP libraries. This was interfaced with two widely used molecular dynamics packages, AMBER and CHARMM. Using the CHARMM-ZAP software combination, the implicit solvent model was tested on eight proteins differing in size, structure, and cofactors: calmodulin, horseradish peroxidase (with and without substrate analogue bound), lipid carrier protein, flavodoxin, ubiquitin, cytochrome c, and a de novo designed 3-helix bundle. The stability and accuracy of the implicit solvent simulations was assessed by examining root-mean-squared deviations from crystal structure. This measure was compared with that of a standard explicit water solvent model. In addition we compared experimental and calculated NMR order parameters to obtain a residue level assessment of the accuracy of MD-ZAP for simulating dynamic quantities. Overall, the agreement of the implicit solvent model with experiment was as good as that of explicit water simulations. The implicit solvent method was up to eight times faster than the explicit water simulations, and approximately four times slower than a vacuum simulation (i.e., with no solvent treatment). (c) 2004 Wiley Periodicals, Inc.

  1. GLYCAM06: A Generalizable Biomolecular Force Field. Carbohydrates

    Science.gov (United States)

    KIRSCHNER, KARL N.; YONGYE, AUSTIN B.; TSCHAMPEL, SARAH M.; GONZÁLEZ-OUTEIRIÑO, JORGE; DANIELS, CHARLISA R.; FOLEY, B. LACHELE; WOODS, ROBERT J.

    2015-01-01

    A new derivation of the GLYCAM06 force field, which removes its previous specificity for carbohydrates, and its dependency on the AMBER force field and parameters, is presented. All pertinent force field terms have been explicitly specified and so no default or generic parameters are employed. The new GLYCAM is no longer limited to any particular class of biomolecules, but is extendible to all molecular classes in the spirit of a small-molecule force field. The torsion terms in the present work were all derived from quantum mechanical data from a collection of minimal molecular fragments and related small molecules. For carbohydrates, there is now a single parameter set applicable to both α- and β-anomers and to all monosaccharide ring sizes and conformations. We demonstrate that deriving dihedral parameters by fitting to QM data for internal rotational energy curves for representative small molecules generally leads to correct rotamer populations in molecular dynamics simulations, and that this approach removes the need for phase corrections in the dihedral terms. However, we note that there are cases where this approach is inadequate. Reported here are the basic components of the new force field as well as an illustration of its extension to carbohydrates. In addition to reproducing the gas-phase properties of an array of small test molecules, condensed-phase simulations employing GLYCAM06 are shown to reproduce rotamer populations for key small molecules and representative biopolymer building blocks in explicit water, as well as crystalline lattice properties, such as unit cell dimensions, and vibrational frequencies. PMID:17849372

  2. Studies of synthetic protein models designed for biomolecular materials applications and model ion channels via molecular dynamics simulations

    Science.gov (United States)

    Zou, Hongling

    MD simulation has become an established and powerful tool to study large macromolecular systems including proteins in explicit solvent. Here simulation is applied to two types of synthetic protein models developed for biomolecular materials applications and for understanding complex biological problems, respectively. The simulation work presented in this thesis aims to facilitate the interpretation of experimental data and to provide detailed structural and dynamic information of protein models inaccessible by experiments. Several synthetic protein models have been investigated in this thesis. Firstly, the structure and dynamics of a de novo designed amphiphilic 4-alpha-helix bundle protein model capable of binding biological metallo-porphyrin cofactors are examined. The simulation results are in agreement with the experimental structural determinations available at lower resolution and limited dimension. Then the work proceeds to incorporate a more comprehensive nonbiological conjugated chromophore into this peptide model. The results show that the protein module plays an important role in controlling the chromophore's conformation and dynamics that are critical to optimize its functionality. Secondly, based on the success of the first work, simulation is utilized to test the viability and help improve the design of two computational designed multi-metalloporphyrins binding protein assemblies, which have different structural features and potential applications. Thirdly, the protein model idea is applied to study the mechanism of the general anesthetic binding as well. The simplified model allows for more sophisticated physical techniques, such as infrared spectroscopy, to be used. MD simulation correctly predicts the infrared frequency shift of the vibrational probes at the binding site in the presence of anesthetics. It also provides the interpretation to the experimental results and reveals the nature of the weak bonding between anesthetics and the model ion

  3. Explicit Instruction Elements in Core Reading Programs

    Science.gov (United States)

    Child, Angela R.

    2012-01-01

    Classroom teachers are provided instructional recommendations for teaching reading from their adopted core reading programs (CRPs). Explicit instruction elements or what is also called instructional moves, including direct explanation, modeling, guided practice, independent practice, discussion, feedback, and monitoring, were examined within CRP…

  4. Sexually explicit media use and relationship satisfaction

    DEFF Research Database (Denmark)

    Veit, Maria; Stulhofer, Aleksandar; Hald, Gert Martin

    2017-01-01

    Using a cross-sectional questionnaire design and a sample of 2284 coupled Croatian adults, this study investigated the association between Sexually Explicit Media (SEM) use and relationship satisfaction. Further, possible moderation of emotional intimacy on the relationship between SEM use and re...

  5. Uncertainty in spatially explicit animal dispersal models

    Science.gov (United States)

    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.

  6. Refinement of protein structures in explicit solvent

    NARCIS (Netherlands)

    Linge, J.P.; Williams, M.A.; Spronk, C.A.E.M.; Bonvin, A.M.J.J.|info:eu-repo/dai/nl/113691238; Nilges, M.

    2003-01-01

    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

  7. Antichrist, Explicit Sex, Anxiety, and Care

    DEFF Research Database (Denmark)

    Grodal, Torben Kragh

    2015-01-01

    The article analyzes how von Trier's Antichrist uses explicit sex to discuss the relation between fear of human embodiment and a longing for care and spiritual intimacy. It discusses how lyrical episodes contrasts descriptions of embodied degradation and experiences of being imprisoned in the body....

  8. Explicit and implicit assessment of gender roles.

    Science.gov (United States)

    Fernández, Juan; Quiroga, M Ángeles; Escorial, Sergio; Privado, Jesús

    2014-05-01

    Gender roles have been assessed by explicit measures and, recently, by implicit measures. In the former case, the theoretical assumptions have been questioned by empirical results. To solve this contradiction, we carried out two concatenated studies based on a relatively well-founded theoretical and empirical approach. The first study was designed to obtain a sample of genderized activities of the domestic sphere by means of an explicit assessment. Forty-two raters (22 women and 20 men, balanced on age, sex, and level of education) took part as raters. In the second study, an implicit assessment of gender roles was carried out, focusing on the response time given to the sample activities obtained from the first study. A total of 164 adults (90 women and 74 men, mean age = 43), with experience in living with a partner and balanced on age, sex, and level of education, participated. Taken together, results show that explicit and implicit assessment converge. The current social reality shows that there is still no equity in some gender roles in the domestic sphere. These consistent results show considerable theoretical and empirical robustness, due to the double implicit and explicit assessment.

  9. Implicit and explicit prejudice and interracial interaction

    NARCIS (Netherlands)

    Dovidio, J.F.; Kawakami, K.L.; Gaertner, S.L.

    2002-01-01

    The present research examined how implicit racial associations and explicit racial attitudes of Whites relate to behaviors and impressions in interracial interactions, Specifically, the authors examined how response latency and self-report measures predicted bias and perceptions of bias in verbal

  10. Orchestrating Semiotic Resources in Explicit Strategy Instruction

    Science.gov (United States)

    Shanahan, Lynn E.; Flury-Kashmanian, Caroline

    2014-01-01

    Research and pedagogical information provided to teachers on implementing explicit strategy instruction has primarily focused on teachers' speech, with limited attention to other modes of communication, such as gesture and artefacts. This interpretive case study investigates two teachers' use of different semiotic resources when introducing…

  11. Sleep Enhances Explicit Recollection in Recognition Memory

    Science.gov (United States)

    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…

  12. A solution for an inverse problem in liquid AFM: calculation of three-dimensional solvation structure on a sample surface

    CERN Document Server

    Amano, Ken-ich

    2013-01-01

    Recent frequency-modulated atomic force microscopy (FM-AFM) can measure three-dimensional force distribution between a probe and a sample surface in liquid. The force distribution is, in the present circumstances, assumed to be solvation structure on the sample surface, because the force distribution and solvation structure have somewhat similar shape. However, the force distribution is exactly not the solvation structure. If we would like to obtain the solvation structure by using the liquid AFM, a method for transforming the force distribution into the solvation structure is necessary. Therefore, in this letter, we present the transforming method in a brief style. We call this method as a solution for an inverse problem, because the solvation structure is obtained at first and the force distribution is obtained next in general calculation processes. The method is formulated (mainly) by statistical mechanics of liquid.

  13. Ramanomics: New Omics Disciplines Using Micro Raman Spectrometry with Biomolecular Component Analysis for Molecular Profiling of Biological Structures.

    Science.gov (United States)

    Kuzmin, Andrey N; Pliss, Artem; Prasad, Paras N

    2017-11-15

    Modern instrumentation for Raman microspectroscopy and current techniques in analysis of spectral data provide new opportunities to study molecular interactions and dynamics at subcellular levels in biological systems. Implementation of biomolecular component analysis (BCA) to microRaman spectrometry provides basis for the emergence of Ramanomics, a new biosensing discipline with unprecedented capabilities to measure concentrations of distinct biomolecular groups in live cells and organelles. Here we review the combined use of microRaman-BCA techniques to probe absolute concentrations of proteins, DNA, RNA and lipids in single organelles of live cells. Assessing biomolecular concentration profiles of organelles at the single cell level provides a physiologically relevant set of biomarkers for cellular heterogeneity. In addition, changes to an organelle's biomolecular concentration profile during a cellular transformation, whether natural, drug induced or disease manifested, can provide molecular insight into the nature of the cellular process.

  14. Solvation structure of ice-binding antifreeze proteins

    Science.gov (United States)

    Hansen-Goos, Hendrik; Wettlaufer, John

    2009-03-01

    Antifreeze proteins (AFPs) can be found in organisms which survive at subzero temperatures. They were first discovered in polar fishes since the 1950's [1] and have been isolated meanwhile also from insects, plants, and bacteria. While AFPs shift the freezing point of water below the bulk melting point and hence can prevent recrystallization; the effect is non-colligative and there is a pronounced hysteresis between freezing and melting. For many AFPs it is generally accepted that they function through an irreversible binding to the ice-water interface which leads to a piecewise convex growth front with a lower nonequilibrium freezing point due to the Kelvin effect. Recent molecular dynamics simulations of the AFP from Choristoneura fumiferana reveal that the solvation structures of water at ice-binding and non-ice-binding faces of the protein are crucial for understanding how the AFP binds to the ice surface and how it is protected from being overgrown [2]. We use density functional theory of classical fluids in order to assess the microscopic solvent structure in the vicinity of protein faces with different surface properties. With our method, binding energies of different protein faces to the water-ice-interface can be computed efficiently in a simplified model. [1] Y. Yeh and R.E. Feeney, Chem. Rev. 96, 601 (1996). [2] D.R. Nutt and J.C. Smith, J. Am. Chem. Soc. 130, 13066 (2008).

  15. Crystallization of Esomeprazole Magnesium Water/Butanol Solvate.

    Science.gov (United States)

    Skieneh, Jenna; Khalili Najafabadi, Bahareh; Horne, Stephen; Rohani, Sohrab

    2016-04-23

    The molecular structure of esomeprazole magnesium derivative in the solid-state is reported for the first time, along with a simplified crystallization pathway. The structure was determined using the single crystal X-ray diffraction technique to reveal the bonding relationships between esomeprazole heteroatoms and magnesium. The esomeprazole crystallization process was carried out in 1-butanol and water was utilized as anti-solvent. The product proved to be esomeprazole magnesium tetrahydrate with two 1-butanol molecules that crystallized in P6₃ space group, in a hexagonal unit cell. Complete characterization of a sample after drying was conducted by the use of powder X-ray diffraction (PXRD), ¹H-nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectroscopy (IR), and dynamic vapor sorption (DVS). Investigation by ¹H-NMR and TGA has shown that the solvent content in the dried sample consists of two water molecules and 0.3 butanol molecules per esomeprazole magnesium molecule. This is different from the single crystal X-ray diffraction results and can be attributed to the loss of some water and 1-butanol molecules stabilized by intermolecular interactions. The title compound, after drying, is a true solvate in terms of water; conversely, 1-butanol fills the voids of the crystal lattice in non-stoichiometric amounts.

  16. Crystallization of Esomeprazole Magnesium Water/Butanol Solvate

    Directory of Open Access Journals (Sweden)

    Jenna Skieneh

    2016-04-01

    Full Text Available The molecular structure of esomeprazole magnesium derivative in the solid-state is reported for the first time, along with a simplified crystallization pathway. The structure was determined using the single crystal X-ray diffraction technique to reveal the bonding relationships between esomeprazole heteroatoms and magnesium. The esomeprazole crystallization process was carried out in 1-butanol and water was utilized as anti-solvent. The product proved to be esomeprazole magnesium tetrahydrate with two 1-butanol molecules that crystallized in P63 space group, in a hexagonal unit cell. Complete characterization of a sample after drying was conducted by the use of powder X-ray diffraction (PXRD, 1H-nuclear magnetic resonance (NMR, thermogravimetric analysis (TGA, differential scanning calorimetry (DSC, infrared spectroscopy (IR, and dynamic vapor sorption (DVS. Investigation by 1H-NMR and TGA has shown that the solvent content in the dried sample consists of two water molecules and 0.3 butanol molecules per esomeprazole magnesium molecule. This is different from the single crystal X-ray diffraction results and can be attributed to the loss of some water and 1-butanol molecules stabilized by intermolecular interactions. The title compound, after drying, is a true solvate in terms of water; conversely, 1-butanol fills the voids of the crystal lattice in non-stoichiometric amounts.

  17. Explicit formulas for regularized products and series

    CERN Document Server

    Jorgenson, Jay; Goldfeld, Dorian

    1994-01-01

    The theory of explicit formulas for regularized products and series forms a natural continuation of the analytic theory developed in LNM 1564. These explicit formulas can be used to describe the quantitative behavior of various objects in analytic number theory and spectral theory. The present book deals with other applications arising from Gaussian test functions, leading to theta inversion formulas and corresponding new types of zeta functions which are Gaussian transforms of theta series rather than Mellin transforms, and satisfy additive functional equations. Their wide range of applications includes the spectral theory of a broad class of manifolds and also the theory of zeta functions in number theory and representation theory. Here the hyperbolic 3-manifolds are given as a significant example.

  18. Implicit and explicit memory bias in anxiety.

    Science.gov (United States)

    Mathews, A; Mogg, K; May, J; Eysenck, M

    1989-08-01

    Previous investigations of recall and recognition for threatening information in clinically anxious subjects have yielded equivocal results. The present study contrasts implicit (word completion) with explicit (cued recall) memory and shows that indices of bias for emotional material derived from the two types of memory are independent of one another. The explicit measure was correlated with trait anxiety scores, but did not clearly distinguish between subjects with clinical anxiety states and normal control subjects. On the implicit memory measure, clinically anxious subjects produced more threat word completions, but only from a set to which they had recently been exposed. These results are taken as evidence that internal representations of threat words are more readily or more persistently activated in anxiety states, although they are not necessarily better elaborated.

  19. Extrapolated stabilized explicit Runge-Kutta methods

    Science.gov (United States)

    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.

  20. Isogeometric Collocation for Elastostatics and Explicit Dynamics

    Science.gov (United States)

    2012-01-25

    of stresses at quadrature points. In this case, storage and compute cost are directly pro- portional to the number of quadrature points. Typical...that is, the one-point Gauss rule. This minimizes storage of stresses and the number of constitutive evaluations and results in an efficient...We confirm the higher-order con- vergence rates of the explicit multi-corrector method on a one-dimensional example and a two dimensional plane strain

  1. Sleep enhances explicit recollection in recognition memory

    OpenAIRE

    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...

  2. Design of an embedded inverse-feedforward biomolecular tracking controller for enzymatic reaction processes.

    Science.gov (United States)

    Foo, Mathias; Kim, Jongrae; Sawlekar, Rucha; Bates, Declan G

    2017-04-06

    Feedback control is widely used in chemical engineering to improve the performance and robustness of chemical processes. Feedback controllers require a 'subtractor' that is able to compute the error between the process output and the reference signal. In the case of embedded biomolecular control circuits, subtractors designed using standard chemical reaction network theory can only realise one-sided subtraction, rendering standard controller design approaches inadequate. Here, we show how a biomolecular controller that allows tracking of required changes in the outputs of enzymatic reaction processes can be designed and implemented within the framework of chemical reaction network theory. The controller architecture employs an inversion-based feedforward controller that compensates for the limitations of the one-sided subtractor that generates the error signals for a feedback controller. The proposed approach requires significantly fewer chemical reactions to implement than alternative designs, and should have wide applicability throughout the fields of synthetic biology and biological engineering.

  3. Exploiting the dynamic properties of covalent modification cycle for the design of synthetic analog biomolecular circuitry.

    Science.gov (United States)

    Foo, Mathias; Sawlekar, Rucha; Bates, Declan G

    2016-01-01

    Cycles of covalent modification are ubiquitous motifs in cellular signalling. Although such signalling cycles are implemented via a highly concise set of chemical reactions, they have been shown to be capable of producing multiple distinct input-output mapping behaviours - ultrasensitive, hyperbolic, signal-transducing and threshold-hyperbolic. In this paper, we show how the set of chemical reactions underlying covalent modification cycles can be exploited for the design of synthetic analog biomolecular circuitry. We show that biomolecular circuits based on the dynamics of covalent modification cycles allow (a) the computation of nonlinear operators using far fewer chemical reactions than purely abstract designs based on chemical reaction network theory, and (b) the design of nonlinear feedback controllers with strong performance and robustness properties. Our designs provide a more efficient route for translation of complex circuits and systems from chemical reactions to DNA strand displacement-based chemistry, thus facilitating their experimental implementation in future Synthetic Biology applications.

  4. Path-sampling strategies for simulating rare events in biomolecular systems.

    Science.gov (United States)

    Chong, Lillian T; Saglam, Ali S; Zuckerman, Daniel M

    2017-04-01

    Despite more than three decades of effort with molecular dynamics simulations, long-timescale (ms and beyond) biologically relevant phenomena remain out of reach in most systems of interest. This is largely because important transitions, such as conformational changes and (un)binding events, tend to be rare for conventional simulations (biomolecular energy landscapes. In contrast, path sampling approaches focus computing effort specifically on transitions of interest. Such approaches have been in use for nearly 20 years in biomolecular systems and enabled the generation of pathways and calculation of rate constants for ms processes, including large protein conformational changes, protein folding, and protein (un)binding. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Controlled Retention and Release of Biomolecular Transport Systems Using Shape-Changing Polymer Bilayers.

    Science.gov (United States)

    Stoychev, Georgi; Reuther, Cordula; Diez, Stefan; Ionov, Leonid

    2016-12-23

    Biomolecular transport systems based on cytoskeletal filaments and motor proteins have become promising tools for a wide range of nanotechnological applications. In this paper, we report control of such transport systems using substrates with switchable shape. We demonstrate this approach on the example of microtubules gliding on surfaces of self-folding polymer bilayers with adsorbed kinesin motors. The polymer bilayers are able to undergo reversible transitions between flat and tube-like shapes that allow the externally controlled retention and release of gliding microtubules. The demonstrated approach, based on surfaces with reconfigurable topography, opens broad perspectives to control biomolecular transport systems for bioanalytical and sensing applications, as well as for the construction of subcellular compartments in the field of synthetic biology. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. A 3D printing method for droplet-based biomolecular materials

    Science.gov (United States)

    Challita, Elio J.; Najem, Joseph S.; Freeman, Eric C.; Leo, Donald J.

    2017-04-01

    The field of developing biomolecular droplet-based materials using a bottom-up approach remains underexplored. Producing tissue-like materials, from entirely synthetic components, presents an innovative method to reconstruct the functions of life within artificial materials. Aqueous droplets, encased with lipid monolayers, may be linked via bilayer interfaces to make up structures that resemble biological tissues. Here we present the design and development of an easy-to-build 3D printer for the fabrication of tissue-like biomolecular materials from cell-sized aqueous droplets. The droplets are generated using a snap off technique, capable of generating 30 droplets per minute. The printed network of droplets may also be functionalized with various types of membrane proteins to achieve desired engineering applications like sensing and actuation, or to mimic electrical communication in biological systems. Voltage sensitive channels are introduced into selected droplets to create a conductive path with the material in the presence of an external field.

  7. Biomolecular imaging and electronic damage using X-ray free-electron lasers

    CERN Document Server

    Quiney, Harry M

    2010-01-01

    Proposals to determine biomolecular structures from diffraction experiments using femtosecond X-ray free-electron laser (XFEL) pulses involve a conflict between the incident brightness required to achieve diffraction-limited atomic resolution and the electronic and structural damage induced by the illumination. Here we show that previous estimates of the conditions under which biomolecular structures may be obtained in this manner are unduly restrictive, because they are based on a coherent diffraction model that is not appropriate to the proposed interaction conditions. A more detailed imaging model derived from optical coherence theory and quantum electrodynamics is shown to be far more tolerant of electronic damage. The nuclear density is employed as the principal descriptor of molecular structure. The foundations of the approach may also be used to characterize electrodynamical processes by performing scattering experiments on complex molecules of known structure.

  8. Explicit solvers in an implicit code

    Science.gov (United States)

    Martinez Montesinos, Beatriz; Kaus, Boris J. P.; Popov, Anton

    2017-04-01

    Many geodynamic processes occur over long timescales (millions of years), and are best solved with implicit solvers. Yet, some processes, such as hydrofracking, or wave propagation, occur over smaller timescales. In those cases, it might be advantageous to use an explicit rather than an implicit approach as it requires significantly less memory and computational costs. Here, we discuss our ongoing work to include explicit solvers in the parallel software package LaMEM (Lithosphere and Mantle Evolution Model). As a first step, we focus on modelling seismic wave propagation in heterogeneous 3D poro-elasto-plastic models. To do that, we add inertial terms to the momentum equations as well as elastic compressibility to the mass conservation equations in an explicit way using the staggered grid finite difference discretization method. Results are similar to that of existing wave propagation codes and are capable to simulate wave propagation in heterogeneous media. To simulate geomechanical problems, timestep restrictions posed by the seismic wave speed are usually too severe to allow simulating deformation on a timescale of months-years. The classical (FLAC) method introduces a mass-density scaling in which a non-physical (larger) density is employed in the momentum equations. We will discuss how this method fits simple benchmarks for elastic and elastoplastic deformation. As an application, we use the code to model different complex media subject to compression and we investigate how mass scaling influence in our results.

  9. Towards an explicit account of implicit learning.

    Science.gov (United States)

    Forkstam, Christian; Petersson, Karl Magnus

    2005-08-01

    The human brain supports acquisition mechanisms that can extract structural regularities implicitly from experience without the induction of an explicit model. Reber defined the process by which an individual comes to respond appropriately to the statistical structure of the input ensemble as implicit learning. He argued that the capacity to generalize to new input is based on the acquisition of abstract representations that reflect underlying structural regularities in the acquisition input. We focus this review of the implicit learning literature on studies published during 2004 and 2005. We will not review studies of repetition priming ('implicit memory'). Instead we focus on two commonly used experimental paradigms: the serial reaction time task and artificial grammar learning. Previous comprehensive reviews can be found in Seger's 1994 article and the Handbook of Implicit Learning. Emerging themes include the interaction between implicit and explicit processes, the role of the medial temporal lobe, developmental aspects of implicit learning, age-dependence, the role of sleep and consolidation. The attempts to characterize the interaction between implicit and explicit learning are promising although not well understood. The same can be said about the role of sleep and consolidation. Despite the fact that lesion studies have relatively consistently suggested that the medial temporal lobe memory system is not necessary for implicit learning, a number of functional magnetic resonance studies have reported medial temporal lobe activation in implicit learning. This issue merits further research. Finally, the clinical relevance of implicit learning remains to be determined.

  10. Intersection Type Systems and Explicit Substitutions Calculi

    Science.gov (United States)

    Ventura, Daniel Lima; Ayala-Rincón, Mauricio; Kamareddine, Fairouz

    The λ-calculus with de Bruijn indices, called λ dB , assembles each α-class of λ-terms into a unique term, using indices instead of variable names. Intersection types provide finitary type polymorphism satisfying important properties like principal typing, which allows the type system to include features such as data abstraction (modularity) and separate compilation. To be closer to computation and to simplify the formalisation of the atomic operations involved in β-contractions, several explicit substitution calculi were developed most of which are written with de Bruijn indices. Although untyped and simply types versions of explicit substitution calculi are well investigated, versions with more elaborate type systems (e.g., with intersection types) are not. In previous work, we presented a version for λ dB of an intersection type system originally introduced to characterise principal typings for β-normal forms and provided the characterisation for this version. In this work we introduce intersection type systems for two explicit substitution calculi: the λσ and the λs e . These type system are based on a type system for λ dB and satisfy the basic property of subject reduction, which guarantees the preservation of types during computations.

  11. Age effects on explicit and implicit memory

    Directory of Open Access Journals (Sweden)

    Emma eWard

    2013-09-01

    Full Text Available It is well documented that explicit memory (e.g., recognition declines with age. In contrast, many argue that implicit memory (e.g., priming is preserved in healthy aging. For example, priming on tasks such as perceptual identification is often not statistically different in groups of young and older adults. Such observations are commonly taken as evidence for distinct explicit and implicit learning/memory systems. In this article we discuss several lines of evidence that challenge this view. We describe how patterns of differential age-related decline may arise from differences in the ways in which the two forms of memory are commonly measured, and review recent research suggesting that under improved measurement methods, implicit memory is not age-invariant. Formal computational models are of considerable utility in revealing the nature of underlying systems. We report the results of applying single and multiple-systems models to data on age effects in implicit and explicit memory. Model comparison clearly favours the single-system view. Implications for the memory systems debate are discussed.

  12. Biomolecular Characterization of Diazotrophs Isolated from the Tropical Soil in Malaysia

    OpenAIRE

    Shamsuddin, Zulkifli H; Qurban Ali Panhwar; Mohammad Abdul Latif; Umme Aminun Naher; Radziah Othman; Puteri Aminatulhawa Megat Amaddin

    2013-01-01

    This study was conducted to evaluate selected biomolecular characteristics of rice root-associated diazotrophs isolated from the Tanjong Karang rice irrigation project area of Malaysia. Soil and rice plant samples were collected from seven soil series belonging to order Inceptisol (USDA soil taxonomy). A total of 38 diazotrophs were isolated using a nitrogen-free medium. The biochemical properties of the isolated bacteria, such as nitrogenase activity, indoleacetic acid (IAA) production and s...

  13. Design of an embedded inverse-feedforward biomolecular tracking controller for enzymatic reaction processes

    OpenAIRE

    Foo, Mathias; Kim, Jongrae; Sawlekar, Rucha; Bates, Declan G.

    2017-01-01

    Feedback control is widely used in chemical engineering to improve the performance and robustness of chemical processes. Feedback controllers require a ?subtractor? that is able to compute the error between the process output and the reference signal. In the case of embedded biomolecular control circuits, subtractors designed using standard chemical reaction network theory can only realise one-sided subtraction, rendering standard controller design approaches inadequate. Here, we show how a b...

  14. Enhanced on-chip SERS based biomolecular detection using electrokinetically active microwells†

    OpenAIRE

    Huh, Yun Suk; Chung, Aram J.; Cordovez, Bernardo; Erickson, David

    2008-01-01

    Here we present a novel microfluidic technique for on-chip surface enhanced Raman spectroscopy (SERS) based biomolecular detection, exploiting the use of electrokinetically active microwells. Briefly, the chip comprises of a series of microfluidic channels containing embedded microwells that, when electrically actuated, either locally attract or repulse species from solution through a combination of electrokinetic effects. We demonstrate that the approach combines the advantages of existing h...

  15. Discovering multi–level structures in bio-molecular data through the Bernstein inequality

    OpenAIRE

    Valentini Giorgio; Bertoni Alberto

    2008-01-01

    Abstract Background The unsupervised discovery of structures (i.e. clusterings) underlying data is a central issue in several branches of bioinformatics. Methods based on the concept of stability have been recently proposed to assess the reliability of a clustering procedure and to estimate the “optimal” number of clusters in bio-molecular data. A major problem with stability-based methods is the detection of multi-level structures (e.g. hierarchical functional classes of genes), and the asse...

  16. Parity Violation in Chiral Molecules: From Theory towards Spectroscopic Experiment and the Evolution of Biomolecular Homochirality

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    The observation of biomolecular homochirality can be considered as a quasi-fossil of the evolution of life [1], the interpretation of which has been an open question for more than a century, with numerous related hypotheses, but no definitive answers. We shall briefly discuss the current status and the relation to the other two questions. The discovery of parity violation led to important developm...

  17. Breaking the polar-nonpolar division in solvation free energy prediction.

    Science.gov (United States)

    Wang, Bao; Wang, Chengzhang; Wu, Kedi; Wei, Guo-Wei

    2017-11-11

    Implicit solvent models divide solvation free energies into polar and nonpolar additive contributions, whereas polar and nonpolar interactions are inseparable and nonadditive. We present a feature functional theory (FFT) framework to break this ad hoc division. The essential ideas of FFT are as follows: (i) representability assumption: there exists a microscopic feature vector that can uniquely characterize and distinguish one molecule from another; (ii) feature-function relationship assumption: the macroscopic features, including solvation free energy, of a molecule is a functional of microscopic feature vectors; and (iii) similarity assumption: molecules with similar microscopic features have similar macroscopic properties, such as solvation free energies. Based on these assumptions, solvation free energy prediction is carried out in the following protocol. First, we construct a molecular microscopic feature vector that is efficient in characterizing the solvation process using quantum mechanics and Poisson-Boltzmann theory. Microscopic feature vectors are combined with macroscopic features, that is, physical observable, to form extended feature vectors. Additionally, we partition a solvation dataset into queries according to molecular compositions. Moreover, for each target molecule, we adopt a machine learning algorithm for its nearest neighbor search, based on the selected microscopic feature vectors. Finally, from the extended feature vectors of obtained nearest neighbors, we construct a functional of solvation free energy, which is employed to predict the solvation free energy of the target molecule. The proposed FFT model has been extensively validated via a large dataset of 668 molecules. The leave-one-out test gives an optimal root-mean-square error (RMSE) of 1.05 kcal/mol. FFT predictions of SAMPL0, SAMPL1, SAMPL2, SAMPL3, and SAMPL4 challenge sets deliver the RMSEs of 0.61, 1.86, 1.64, 0.86, and 1.14 kcal/mol, respectively. Using a test set of 94

  18. Biomolecular Force Field Parameterization via Atoms-in-Molecule Electron Density Partitioning.

    Science.gov (United States)

    Cole, Daniel J; Vilseck, Jonah Z; Tirado-Rives, Julian; Payne, Mike C; Jorgensen, William L

    2016-05-10

    Molecular mechanics force fields, which are commonly used in biomolecular modeling and computer-aided drug design, typically treat nonbonded interactions using a limited library of empirical parameters that are developed for small molecules. This approach does not account for polarization in larger molecules or proteins, and the parametrization process is labor-intensive. Using linear-scaling density functional theory and atoms-in-molecule electron density partitioning, environment-specific charges and Lennard-Jones parameters are derived directly from quantum mechanical calculations for use in biomolecular modeling of organic and biomolecular systems. The proposed methods significantly reduce the number of empirical parameters needed to construct molecular mechanics force fields, naturally include polarization effects in charge and Lennard-Jones parameters, and scale well to systems comprised of thousands of atoms, including proteins. The feasibility and benefits of this approach are demonstrated by computing free energies of hydration, properties of pure liquids, and the relative binding free energies of indole and benzofuran to the L99A mutant of T4 lysozyme.

  19. Rational Design of Biomolecular Templates for Synthesizing Multifunctional Noble Metal Nanoclusters toward Personalized Theranostic Applications.

    Science.gov (United States)

    Yu, Yong; Mok, Beverly Y L; Loh, Xian Jun; Tan, Yen Nee

    2016-08-01

    Biomolecule-templated or biotemplated metal nanoclusters (NCs) are ultrasmall (biomolecular template (e.g., peptides, proteins, and DNA). Due to their unique physiochemical properties, biotemplated metal NCs have been widely used in sensing, imaging, delivery and therapy. The overwhelming applications in these individual areas imply the great promise of harnessing biotemplated metal NCs in more advanced biomedical aspects such as theranostics. Although applications of biotemplated metal NCs as theranostic agents are trending, the rational design of biomolecular templates suitable for the synthesis of multifunctional metal NCs for theranostics is comparatively underexplored. This progress report first identifies the essential attributes of biotemplated metal NCs for theranostics by reviewing the state-of-art applications in each of the four modalities of theranostics, namely sensing, imaging, delivery and therapy. To achieve high efficacy in these modalities, we elucidate the design principles underlying the use of biomolecules (proteins, peptides and nucleic acids) to control the NC size, emission color and surface chemistries for post-functionalization of therapeutic moieties. We then propose a unified strategy to engineer biomolecular templates that combine all these modalities to produce multifunctional biotemplated metal NCs that can serve as the next-generation personalized theranostic agents. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Single-Layer Ternary Chalcogenide Nanosheet as a Fluorescence-Based "Capture-Release" Biomolecular Nanosensor.

    Science.gov (United States)

    Kenry; Geldert, Alisha; Lai, Zhuangchai; Huang, Ying; Yu, Peng; Tan, Chaoliang; Liu, Zheng; Zhang, Hua; Lim, Chwee Teck

    2017-02-01

    The novel application of two-dimensional (2D) single-layer ternary chalcogenide nanosheets as "capture-release" fluorescence-based biomolecular nanosensors is demonstrated. Fluorescently labeled biomolecular probe is first captured by the ultrathin Ta2 NiS5 nanosheets and then released upon adding analyte containing a target biomolecule due to the higher probe-target affinity. Here, the authors use a nucleic acid probe for the model target biomolecule Plasmodium lactate dehydrogenase, which is an important malarial biomarker. The ultrathin Ta2 NiS5 nanosheet serves as a highly efficient fluorescence quencher and the nanosensor developed from the nanosheet is highly sensitive and specific toward the target biomolecule. Apart from the specificity toward the target biomolecule in homogeneous solutions, the developed nanosensor is capable of detecting and differentiating the target in heterogeneous solutions consisting of either a mixture of biomolecules or serum, with exceptional specificity. The simplicity of the "capture-release" method, by eliminating the need for preincubation of the probe with the test sample, may facilitate further development of portable and rapid biosensors. The authors anticipate that this ternary chalcogenide nanosheet-based biomolecular nanosensor will be useful for the rapid detection and differentiation of a wide range of chemical and biological species. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. ssDNA-Functionalized Nanoceria: A Redox-Active Aptaswitch for Biomolecular Recognition.

    Science.gov (United States)

    Bülbül, Gonca; Hayat, Akhtar; Andreescu, Silvana

    2016-04-06

    Quantification of biomolecular binding events is a critical step for the development of biorecognition assays for diagnostics and therapeutic applications. This paper reports the design of redox-active switches based on aptamer conjugated nanoceria for detection and quantification of biomolecular recognition. It is shown that the conformational transition state of the aptamer on nanoceria, combined with the redox properties of these particles can be used to create surface based structure switchable aptasensing platforms. Changes in the redox properties at the nanoceria surface upon binding of the ssDNA and its target analyte enables rapid and highly sensitive measurement of biomolecular interactions. This concept is demonstrated as a general applicable method to the colorimetric detection of DNA binding events. An example of a nanoceria aptaswitch for the colorimetric sensing of Ochratoxin A (OTA) and applicability to other targets is provided. The system can sensitively and selectivity detect as low as 0.15 × 10(-9) m OTA. This novel assay is simple in design and does not involve oligonucleotide labeling or elaborate nanoparticle modification steps. The proposed mechanism discovered here opens up a new way of designing optical sensing methods based on aptamer recognition. This approach can be broadly applicable to many bimolecular recognition processes and related applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Minimum steering node set of complex networks and its applications to biomolecular networks.

    Science.gov (United States)

    Wu, Lin; Li, Min; Wang, Jianxin; Wu, Fang-Xiang

    2016-06-01

    Many systems of interests in practices can be represented as complex networks. For biological systems, biomolecules do not perform their functions alone but interact with each other to form so-called biomolecular networks. A system is said to be controllable if it can be steered from any initial state to any other final state in finite time. The network controllability has become essential to study the dynamics of the networks and understand the importance of individual nodes in the networks. Some interesting biological phenomena have been discovered in terms of the structural controllability of biomolecular networks. Most of current studies investigate the structural controllability of networks in notion of the minimum driver node sets (MDSs). In this study, the authors analyse the network structural controllability in notion of the minimum steering node sets (MSSs). They first develop a graph-theoretic algorithm to identify the MSS for a given network and then apply it to several biomolecular networks. Application results show that biomolecules identified in the MSSs play essential roles in corresponding biological processes. Furthermore, the application results indicate that the MSSs can reflect the network dynamics and node importance in controlling the networks better than the MDSs.

  3. Multi-core CPU or GPU-accelerated Multiscale Modeling for Biomolecular Complexes.

    Science.gov (United States)

    Liao, Tao; Zhang, Yongjie; Kekenes-Huskey, Peter M; Cheng, Yuhui; Michailova, Anushka; McCulloch, Andrew D; Holst, Michael; McCammon, J Andrew

    2013-07-01

    Multi-scale modeling plays an important role in understanding the structure and biological functionalities of large biomolecular complexes. In this paper, we present an efficient computational framework to construct multi-scale models from atomic resolution data in the Protein Data Bank (PDB), which is accelerated by multi-core CPU and programmable Graphics Processing Units (GPU). A multi-level summation of Gaus-sian kernel functions is employed to generate implicit models for biomolecules. The coefficients in the summation are designed as functions of the structure indices, which specify the structures at a certain level and enable a local resolution control on the biomolecular surface. A method called neighboring search is adopted to locate the grid points close to the expected biomolecular surface, and reduce the number of grids to be analyzed. For a specific grid point, a KD-tree or bounding volume hierarchy is applied to search for the atoms contributing to its density computation, and faraway atoms are ignored due to the decay of Gaussian kernel functions. In addition to density map construction, three modes are also employed and compared during mesh generation and quality improvement to generate high quality tetrahedral meshes: CPU sequential, multi-core CPU parallel and GPU parallel. We have applied our algorithm to several large proteins and obtained good results.

  4. Architecture of transcriptional regulatory circuits is knitted over the topology of bio-molecular interaction networks

    Directory of Open Access Journals (Sweden)

    Nielsen Jens

    2008-02-01

    Full Text Available Abstract Background Uncovering the operating principles underlying cellular processes by using 'omics' data is often a difficult task due to the high-dimensionality of the solution space that spans all interactions among the bio-molecules under consideration. A rational way to overcome this problem is to use the topology of bio-molecular interaction networks in order to constrain the solution space. Such approaches systematically integrate the existing biological knowledge with the 'omics' data. Results Here we introduce a hypothesis-driven method that integrates bio-molecular network topology with transcriptome data, thereby allowing the identification of key biological features (Reporter Features around which transcriptional changes are significantly concentrated. We have combined transcriptome data with different biological networks in order to identify Reporter Gene Ontologies, Reporter Transcription Factors, Reporter Proteins and Reporter Complexes, and use this to decipher the logic of regulatory circuits playing a key role in yeast glucose repression and human diabetes. Conclusion Reporter Features offer the opportunity to identify regulatory hot-spots in bio-molecular interaction networks that are significantly affected between or across conditions. Results of the Reporter Feature analysis not only provide a snapshot of the transcriptional regulatory program but also are biologically easy to interpret and provide a powerful way to generate new hypotheses. Our Reporter Features analyses of yeast glucose repression and human diabetes data brings hints towards the understanding of the principles of transcriptional regulation controlling these two important and potentially closely related systems.

  5. Update of KDBI: Kinetic Data of Bio-molecular Interaction database.

    Science.gov (United States)

    Kumar, Pankaj; Han, B C; Shi, Z; Jia, J; Wang, Y P; Zhang, Y T; Liang, L; Liu, Q F; Ji, Z L; Chen, Y Z

    2009-01-01

    Knowledge of the kinetics of biomolecular interactions is important for facilitating the study of cellular processes and underlying molecular events, and is essential for quantitative study and simulation of biological systems. Kinetic Data of Bio-molecular Interaction database (KDBI) has been developed to provide information about experimentally determined kinetic data of protein-protein, protein-nucleic acid, protein-ligand, nucleic acid-ligand binding or reaction events described in the literature. To accommodate increasing demand for studying and simulating biological systems, numerous improvements and updates have been made to KDBI, including new ways to access data by pathway and molecule names, data file in System Biology Markup Language format, more efficient search engine, access to published parameter sets of simulation models of 63 pathways, and 2.3-fold increase of data (19,263 entries of 10,532 distinctive biomolecular binding and 11,954 interaction events, involving 2635 proteins/protein complexes, 847 nucleic acids, 1603 small molecules and 45 multi-step processes). KDBI is publically available at http://bidd.nus.edu.sg/group/kdbi/kdbi.asp.

  6. Reverse engineering biomolecular systems using -omic data: challenges, progress and opportunities.

    Science.gov (United States)

    Quo, Chang F; Kaddi, Chanchala; Phan, John H; Zollanvari, Amin; Xu, Mingqing; Wang, May D; Alterovitz, Gil

    2012-07-01

    Recent advances in high-throughput biotechnologies have led to the rapid growing research interest in reverse engineering of biomolecular systems (REBMS). 'Data-driven' approaches, i.e. data mining, can be used to extract patterns from large volumes of biochemical data at molecular-level resolution while 'design-driven' approaches, i.e. systems modeling, can be used to simulate emergent system properties. Consequently, both data- and design-driven approaches applied to -omic data may lead to novel insights in reverse engineering biological systems that could not be expected before using low-throughput platforms. However, there exist several challenges in this fast growing field of reverse engineering biomolecular systems: (i) to integrate heterogeneous biochemical data for data mining, (ii) to combine top-down and bottom-up approaches for systems modeling and (iii) to validate system models experimentally. In addition to reviewing progress made by the community and opportunities encountered in addressing these challenges, we explore the emerging field of synthetic biology, which is an exciting approach to validate and analyze theoretical system models directly through experimental synthesis, i.e. analysis-by-synthesis. The ultimate goal is to address the present and future challenges in reverse engineering biomolecular systems (REBMS) using integrated workflow of data mining, systems modeling and synthetic biology.

  7. Reverse engineering biomolecular systems using −omic data: challenges, progress and opportunities

    Science.gov (United States)

    Quo, Chang F.; Kaddi, Chanchala; Phan, John H.; Zollanvari, Amin; Xu, Mingqing

    2012-01-01

    Recent advances in high-throughput biotechnologies have led to the rapid growing research interest in reverse engineering of biomolecular systems (REBMS). ‘Data-driven’ approaches, i.e. data mining, can be used to extract patterns from large volumes of biochemical data at molecular-level resolution while ‘design-driven’ approaches, i.e. systems modeling, can be used to simulate emergent system properties. Consequently, both data- and design-driven approaches applied to –omic data may lead to novel insights in reverse engineering biological systems that could not be expected before using low-throughput platforms. However, there exist several challenges in this fast growing field of reverse engineering biomolecular systems: (i) to integrate heterogeneous biochemical data for data mining, (ii) to combine top–down and bottom–up approaches for systems modeling and (iii) to validate system models experimentally. In addition to reviewing progress made by the community and opportunities encountered in addressing these challenges, we explore the emerging field of synthetic biology, which is an exciting approach to validate and analyze theoretical system models directly through experimental synthesis, i.e. analysis-by-synthesis. The ultimate goal is to address the present and future challenges in reverse engineering biomolecular systems (REBMS) using integrated workflow of data mining, systems modeling and synthetic biology. PMID:22833495

  8. Understanding Lithium Solvation and Diffusion through Topological Analysis of First-Principles Molecular Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Bhatia, Harsh [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Gyulassy, Attila [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Ong, Mitchell [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Lordi, Vincenzo [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Draeger, Erik [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Pask, John [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Pascucci, Valerio [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Bremer, Peer -Timo [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-09-27

    The performance of lithium-ion batteries is strongly influenced by the ionic conductivity of the electrolyte, which depends on the speed at which Li ions migrate across the cell and relates to their solvation structure. The choice of solvent can greatly impact, both, the solvation and diffusivity of Li ions. In this work, we present our application of the topological techniques to extract and predict such behavior in the data generated by the first-principles molecular dynamics simulation of Li ions in an important organic solvent -ethylene carbonate. More specifically, we use the scalar topology of the electron charge density field to analyze the evolution of the solvation structures. This allows us to derive a parameter-free bond definition for lithium-oxygen bonds, to provide a quantitative measure for bond strength, and to understand the regions of influence of each atom in the simulation. This has provided new insights into how and under what conditions certain bonds may form and break. As a result, we can identify and, more importantly, predict, unstable configurations in solvation structures. This can be very useful in understanding when small changes to the atoms' movements can cause significantly different bond structures to evolve. Ultimately, this promises to allow scientists to explore lithium ion solvation and diffusion more systematically, with the aim of new insights and potentially accelerating the calculations themselves.

  9. Thermodynamic Functions of Solvation of Hydrocarbons, Noble Gases, and Hard Spheres in Tetrahydrofuran-Water Mixtures.

    Science.gov (United States)

    Sedov, I A; Magsumov, T I

    2015-07-16

    Thermodynamic solvation properties of mixtures of water with tetrahydrofuran at 298 K are studied. The Gibbs free energies and enthalpies of solvation of n-octane and toluene are determined experimentally. For molecular dynamics simulations of the binary solvent, we have modified a TraPPE-UA model for tetrahydrofuran and combined it with the SPC/E potential for water. The excess thermodynamic functions of neon, xenon, and hard spheres with two different radii are calculated using the particle insertion method. Simulated and real systems share the same characteristic trends for the thermodynamic functions. A maximum is present on dependencies of the enthalpy of solvation from the composition of solvent at 70-90 mol % water, making it higher than in both of the cosolvents. It is caused by a high enthalpy of cavity formation in the mixtures rich with water due to solvent reorganization around the cavity, which is shown by calculation of the enthalpy of solvation of hard spheres. Addition of relatively small amounts of tetrahydrofuran to water effectively suppresses the hydrophobic effect, leading to a quick increase of both the entropy and enthalpy of cavity formation and solvation of low polar molecules.

  10. Electrostatic solvation free energies of charged hard spheres using molecular dynamics with density functional theory interactions

    Science.gov (United States)

    Duignan, Timothy T.; Baer, Marcel D.; Schenter, Gregory K.; Mundy, Chistopher J.

    2017-10-01

    Determining the solvation free energies of single ions in water is one of the most fundamental problems in physical chemistry and yet many unresolved questions remain. In particular, the ability to decompose the solvation free energy into simple and intuitive contributions will have important implications for models of electrolyte solution. Here, we provide definitions of the various types of single ion solvation free energies based on different simulation protocols. We calculate solvation free energies of charged hard spheres using density functional theory interaction potentials with molecular dynamics simulation and isolate the effects of charge and cavitation, comparing to the Born (linear response) model. We show that using uncorrected Ewald summation leads to unphysical values for the single ion solvation free energy and that charging free energies for cations are approximately linear as a function of charge but that there is a small non-linearity for small anions. The charge hydration asymmetry for hard spheres, determined with quantum mechanics, is much larger than for the analogous real ions. This suggests that real ions, particularly anions, are significantly more complex than simple charged hard spheres, a commonly employed representation.

  11. Tuning solid-state blue and red luminescence by the formation of solvate crystals.

    Science.gov (United States)

    Yan, Dongpeng; Fan, Guoling; Guan, Yan; Meng, Qingyun; Li, Congju; Wang, Jiaona

    2013-12-07

    Tuning and controlling the solid-state luminescence of molecular solids play a key role in developing multi-color displays and tunable dye laser. In this work, we report the tunable blue and red luminescence by the formation of solvate crystals of 1,4-bis(5-phenyl-2-oxazolyl)benzene (POPOP) and 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM). Upon introduction of guest solvents (chloroform and dichloromethane) into the POPOP and DCM host matrices, the obtained solvate crystals exhibit an alternated stacking arrangement, interaction fashion, and crystal symmetry compared with the pristine chromophore solids. Furthermore, the solvates of POPOP (CCl3H) and DCM (CCl2H2) present changeable luminescent properties (such as one-/two-photon emissive wavelength, fluorescence lifetime and photoluminescent quantum yield) in the blue/red regions relative to the pristine POPOP and DCM. In addition, the second harmonic generation can also be obtained for the DCM (CCl2H2) due to the transformation of the centrosymmetric to a non-centrosymmetric structure from pristine DCM. Periodic density functional theoretical calculations suggest that the guest solvents do not participate in the frontier orbital distribution within the solvate crystals. Therefore, by the combination of experimental and theoretical studies on the solvate crystals, this work not only reports the supramolecular assembly of new types of host-guest photoactive systems, but also provides a detailed understanding of the electronic structures of the solid-state luminescent materials.

  12. Solvation pressure as real pressure: I. Ethanol and starch under negative pressure

    CERN Document Server

    Uden, N W A V; Faux, D A; Tanczos, A C; Howlin, B; Dunstan, D J

    2003-01-01

    The reality of the solvation pressure generated by the cohesive energy density of liquids is demonstrated by three methods. Firstly, the Raman spectrum of ethanol as a function of cohesive energy density (solvation pressure) in ethanol-water and ethanol-chloroform mixtures is compared with the Raman spectrum of pure ethanol under external hydrostatic pressure and the solvation pressure and hydrostatic pressure are found to be equivalent for some transitions. Secondly, the bond lengths of ethanol are calculated by molecular dynamics modelling for liquid ethanol under pressure and for ethanol vapour. The difference in bond lengths between vapour and liquid are found to be equivalent to the solvation pressure for the C-H sub 3 , C-H sub 2 and O-H bond lengths, with discrepancies for the C-C and C-O bond lengths. Thirdly, the pressure-induced gelation of potato starch is measured in pure water and in mixtures of water and ethanol. The phase transition pressure varies in accordance with the change in solvation pre...

  13. Density Functional Theory Calculation of pKa's of Thiols in Aqueous Solution Using Explicit Water Molecules and the Polarizable Continuum Model.

    Science.gov (United States)

    Thapa, Bishnu; Schlegel, H Bernhard

    2016-07-21

    The pKa's of substituted thiols are important for understanding their properties and reactivities in applications in chemistry, biochemistry, and material chemistry. For a collection of 175 different density functionals and the SMD implicit solvation model, the average errors in the calculated pKa's of methanethiol and ethanethiol are almost 10 pKa units higher than for imidazole. A test set of 45 substituted thiols with pKa's ranging from 4 to 12 has been used to assess the performance of 8 functionals with 3 different basis sets. As expected, the basis set needs to include polarization functions on the hydrogens and diffuse functions on the heavy atoms. Solvent cavity scaling was ineffective in correcting the errors in the calculated pKa's. Inclusion of an explicit water molecule that is hydrogen bonded with the H of the thiol group (in neutral) or S(-) (in thiolates) lowers error by an average of 3.5 pKa units. With one explicit water and the SMD solvation model, pKa's calculated with the M06-2X, PBEPBE, BP86, and LC-BLYP functionals are found to deviate from the experimental values by about 1.5-2.0 pKa units whereas pKa's with the B3LYP, ωB97XD and PBEVWN5 functionals are still in error by more than 3 pKa units. The inclusion of three explicit water molecules lowers the calculated pKa further by about 4.5 pKa units. With the B3LYP and ωB97XD functionals, the calculated pKa's are within one unit of the experimental values whereas most other functionals used in this study underestimate the pKa's. This study shows that the ωB97XD functional with the 6-31+G(d,p) and 6-311++G(d,p) basis sets, and the SMD solvation model with three explicit water molecules hydrogen bonded to the sulfur produces the best result for the test set (average error -0.11 ± 0.50 and +0.15 ± 0.58, respectively). The B3LYP functional also performs well (average error -1.11 ± 0.82 and -0.78 ± 0.79, respectively).

  14. Single-Ion Solvation Free Energies and the Normal Hydrogen Electrode Potential in Methanol, Acetonitrile, and Dimethyl Sulfoxide

    Science.gov (United States)

    Kelly, Casey P.; Cramer, Christopher J.; Truhlar, Donald G.

    2008-01-01

    The division of thermodynamic solvation free energies of electrolytes into ionic constituents is conventionally accomplished by using the single-ion solvation free energy of one reference ion, conventionally the proton, to set the single-ion scales. Thus the determination of the free energy of solvation of the proton in various solvents is a fundamental issue of central importance in solution chemistry. In the present article, relative solvation free energies of ions and ion-solvent clusters in methanol, acetonitrile, and dimethyl sulfoxide (DMSO) have been determined using a combination of experimental and theoretical gas-phase free energies of formation, solution-phase reduction potentials and acid dissociation constants, and gas-phase clustering free energies. Applying the cluster pair approximation to differences between these relative solvation free energies leads to values of −263.5, −260.2, and −273.3 kcal/mol for the absolute solvation free energy of the proton in methanol, acetonitrile, and DMSO, respectively. The final absolute proton solvation free energies are used to assign absolute values for the normal hydrogen electrode potential and the solvation free energies of other single ions in the above solvents. PMID:17214493

  15. The solvation of NaCl in model water with different hydrogen bond strength.

    Science.gov (United States)

    Gu, B; Zhang, F S; Wang, Z P; Zhou, H Y

    2008-11-14

    Based on hybrid water models, we design a series of solvent environments with different hydrogen bond strength and study the solvation of NaCl in them. The microstructures and dynamical behaviors of solvents and ion solutes are presented in detail to trace the correlations between the hydrogen bond strength of water and the solvation mechanism of the ions. In the process of the solvation of NaCl, the balance of the competition between breaking original solvent structures and formation of hydration shells around ions is sensitive to the hydrogen bonding ability of water. The results indicate that NaCl is most ideally dissolved in natural water with the strongest hydration effects around both cations and anions. In solvents with both reduced and enhanced hydrogen bond strength, the ions are more inclined to be in contact or aggregate into clusters of different sizes. These phenomena show that appropriate hydrogen bond strength is crucial for water's natural dissolving capacity.

  16. High pressure infrared spectroscopy study on C60∗CS2 solvates

    Science.gov (United States)

    Du, Mingrun; Zhou, Miao; Yao, Mingguang; Ge, Peng; Chen, Shuanglong; Yang, Xigui; Liu, Ran; Liu, Bo; Cui, Tian; Sundqvist, Bertil; Liu, Bingbing

    2017-02-01

    High pressure IR study has been carried out on C60∗CS2 solvates up to 34.8 GPa. It is found that the intercalated CS2 molecules significantly affect the transformations of C60 molecules under pressure. As a probe, the intercalated CS2 molecules can well detect the orientational ordering transition and deformation of C60 molecules under pressure. The chemical stability of CS2 molecules under pressure is also dramatically enhanced due to the spacial shielding effet from C60 molecules around in the solvated crystal. These results provide new insight into the effect of interactions between intercalants and fullerenes on the transformations in fullerene solvates under pressure.

  17. Atomistic characterization of the active-site solvation dynamics of a model photocatalyst

    Science.gov (United States)

    van Driel, Tim B.; Kjær, Kasper S.; Hartsock, Robert W.; Dohn, Asmus O.; Harlang, Tobias; Chollet, Matthieu; Christensen, Morten; Gawelda, Wojciech; Henriksen, Niels E.; Kim, Jong Goo; Haldrup, Kristoffer; Kim, Kyung Hwan; Ihee, Hyotcherl; Kim, Jeongho; Lemke, Henrik; Sun, Zheng; Sundström, Villy; Zhang, Wenkai; Zhu, Diling; Møller, Klaus B.; Nielsen, Martin M.; Gaffney, Kelly J.

    2016-11-01

    The interactions between the reactive excited state of molecular photocatalysts and surrounding solvent dictate reaction mechanisms and pathways, but are not readily accessible to conventional optical spectroscopic techniques. Here we report an investigation of the structural and solvation dynamics following excitation of a model photocatalytic molecular system [Ir2(dimen)4]2+, where dimen is para-diisocyanomenthane. The time-dependent structural changes in this model photocatalyst, as well as the changes in the solvation shell structure, have been measured with ultrafast diffuse X-ray scattering and simulated with Born-Oppenheimer Molecular Dynamics. Both methods provide direct access to the solute-solvent pair distribution function, enabling the solvation dynamics around the catalytically active iridium sites to be robustly characterized. Our results provide evidence for the coordination of the iridium atoms by the acetonitrile solvent and demonstrate the viability of using diffuse X-ray scattering at free-electron laser sources for studying the dynamics of photocatalysis.

  18. Evaluation of electronic polarization energy in oligoacene molecular crystals using the solvated supermolecular approach.

    Science.gov (United States)

    Xu, Tao; Wang, Wenliang; Yin, Shiwei; Wang, Yun

    2017-06-07

    The solvated supermolecular approach, i.e., block-localized wave function coupled with polarizable continuum model (BLW/PCM), was proposed to calculate molecular ionization potential (IP), electron affinity (EA) in the solid phase, and related electronic polarization. Via the calculations of a solvated supermolecule (5M), including four closest molecules, BLW/PCM overcomes the limitation in the calculation for the monomer PCM, that is, nearly same electronic polarization for cation (P + ) and anion (P - ). The solvated supermolecular approach successfully described asymmetric behaviors of P + and P - for oligoacene crystals. In addition, we also compared two charge-localized methods, i.e., BLW and constrained density functional theory (CDFT), to calculate the molecular IP and EA in supermolecules with/without PCM. Our results demonstrate that both the BLW and CDFT correctly estimate the EA and IP values in the gas phase cluster, whereas CDFT/PCM fails to evaluate the P - value of the bulk system.

  19. THE PREFERENTIAL STRUCTURE OF Co2+ SOLVATION IN AQUEOUS AMMONIA SOLUTION DETERMINING BY MONTE CARLO SIMULATION

    Directory of Open Access Journals (Sweden)

    Cahyorini Kusumawardani

    2010-06-01

    Full Text Available A Monte Carlo simulation was performed for Co2+ in 18.6 % aqueous ammonia solution at a temperature of 293.16 K, using ab initio pair potentials and three-body potentials for Co-H2O-H2O, Co-NH3-NH3 and Co-H2O-NH3 interactions. The first solvation shell consists average of 2.9 water and 3.2 ammonia molecules, and the second shell of 10.4 water and 11.2 ammonia molecules. The structure of the solvated ion is discussed in terms of radial distribution functions, angular distributions and coordination number.   Keywords: Molecular simulation, Monte Carlo simulation, solvation, ab initio

  20. Subpicosecond resolution studies of solvation dynamics in polar aprotic and alcohol solvents

    Science.gov (United States)

    Castner, Edward W., Jr.; Maroncelli, Mark; Fleming, Graham R.

    1987-02-01

    Subpicosecond resolution measurements of the kinetics of dipolar solvation have been made. The time resolved Stokes shift of a dye molecule, LDS-750 was measured using the fluorescence upconversion technique in the solvents acetonitrile, DMSO, nitrobenzene, methanol, and n-butanol. The solvation dynamics in both aprotic and alcohol solvents occur on a time scale roughly given by the longitudinal relaxation time as predicted by simple continuum theories. The relaxation in nitrobenzene and butanol is nonexponential and the relaxation in methanol is significantly faster than the calculated time. These deviations from simple theory are discussed in the context of (i) the significance of high frequency dispersions in the dielectric response, (ii) translational contributions to the solvent relaxation, and (iii) molecular aspects of the solvation not accounted in the continuum description.

  1. Explicit and implicit modeling of nanobubbles in hydrophobic confinement

    Directory of Open Access Journals (Sweden)

    Joachim Dzubiella

    2010-03-01

    Full Text Available Water at normal conditions is a fluid thermodynamically close to the liquid-vapor phase coexistence and features a large surface tension. This combination can lead to interesting capillary phenomena on microscopic scales. Explicit water molecular dynamics (MD computer simulations of hydrophobic solutes, for instance, give evidence of capillary evaporation on nanometer scales, i.e., the formation of nanometer-sized vapor bubbles (nanobubbles between confining hydrophobic surfaces. This phenomenon has been exemplified for solutes with varying complexity, e.g., paraffin plates, coarse-grained homopolymers, biological and solid-state channels, and atomistically resolved proteins. It has been argued that nanobubbles strongly impact interactions in nanofluidic devices, translocation processes, and even in protein stability, function, and folding. As large-scale MD simulations are computationally expensive, the efficient multiscale modeling of nanobubbles and the prediction of their stability poses a formidable task to the'nanophysical' community. Recently, we have presented a conceptually novel and versatile implicit solvent model, namely, the variational implicit solvent model (VISM, which is based on a geometric energy functional. As reviewed here, first solvation studies of simple hydrophobic solutes using VISM coupled with the numerical level-set scheme show promising results, and, in particular, capture nanobubble formation and its subtle competition to local energetic potentials in hydrophobic confinement.Água em condições normais consiste de um fluido termodinamicamente próximo à fase líquida-vapor exibindo alta tensão superficial. Esta combinação conduz a fenômenos capilares interessantes na escala microscópica. Simulações computacionais baseadas em técnicas de Dinâmica Molecular em solutos hidrofóbicos por exemplo fornecem evidências do fenômeno de evaporação capilar em escalas nanométricas dando origem à formação de

  2. Explicit criteria for prioritization of cataract surgery

    Directory of Open Access Journals (Sweden)

    Escobar Antonio

    2006-03-01

    Full Text Available Abstract Background Consensus techniques have been used previously to create explicit criteria to prioritize cataract extraction; however, the appropriateness of the intervention was not included explicitly in previous studies. We developed a prioritization tool for cataract extraction according to the RAND method. Methods Criteria were developed using a modified Delphi panel judgment process. A panel of 11 ophthalmologists was assembled. Ratings were analyzed regarding the level of agreement among panelists. We studied the effect of all variables on the final panel score using general linear and logistic regression models. Priority scoring systems were developed by means of optimal scaling and general linear models. The explicit criteria developed were summarized by means of regression tree analysis. Results Eight variables were considered to create the indications. Of the 310 indications that the panel evaluated, 22.6% were considered high priority, 52.3% intermediate priority, and 25.2% low priority. Agreement was reached for 31.9% of the indications and disagreement for 0.3%. Logistic regression and general linear models showed that the preoperative visual acuity of the cataractous eye, visual function, and anticipated visual acuity postoperatively were the most influential variables. Alternative and simple scoring systems were obtained by optimal scaling and general linear models where the previous variables were also the most important. The decision tree also shows the importance of the previous variables and the appropriateness of the intervention. Conclusion Our results showed acceptable validity as an evaluation and management tool for prioritizing cataract extraction. It also provides easy algorithms for use in clinical practice.

  3. Implicit and explicit timing in oculomotor control.

    Directory of Open Access Journals (Sweden)

    Ilhame Ameqrane

    Full Text Available The passage of time can be estimated either explicitly, e.g. before leaving home in the morning, or implicitly, e.g. when catching a flying ball. In the present study, the latency of saccadic eye movements was used to evaluate differences between implicit and explicit timing. Humans were required to make a saccade between a central and a peripheral position on a computer screen. The delay between the extinction of a central target and the appearance of an eccentric target was the independent variable that could take one out of four different values (400, 900, 1400 or 1900 ms. In target trials, the delay period lasted for one of the four durations randomly. At the end of the delay, a saccade was initiated by the appearance of an eccentric target. Cue&target trials were similar to target trials but the duration of the delay was visually cued. In probe trials, the duration of the upcoming delay was cued, but there was no eccentric target and subjects had to internally generate a saccade at the estimated end of the delay. In target and cue&target trials, the mean and variance of latency distributions decreased as delay duration increased. In cue&target trials latencies were shorter. In probe trials, the variance increased with increasing delay duration and scalar variability was observed. The major differences in saccadic latency distributions were observed between visually-guided (target and cue&target trials and internally-generated saccades (probe trials. In target and cue&target trials the timing of the response was implicit. In probe trials, the timing of the response was internally-generated and explicitly based on the duration of the visual cue. Scalar timing was observed only during probe trials. This study supports the hypothesis that there is no ubiquitous timing system in the brain but independent timing processes active depending on task demands.

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

    Directory of Open Access Journals (Sweden)

    Siengsukon CF

    2011-06-01

    Full Text Available Catherine F Siengsukon, Alham Al-SharmanDepartment of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, KS, USABackground: 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

  5. Spatially explicit non-Mendelian diploid model

    OpenAIRE

    Lanchier, N.; Neuhauser, C.

    2009-01-01

    We introduce a spatially explicit model for the competition between type $a$ and type $b$ alleles. Each vertex of the $d$-dimensional integer lattice is occupied by a diploid individual, which is in one of three possible states or genotypes: $aa$, $ab$ or $bb$. We are interested in the long-term behavior of the gene frequencies when Mendel's law of segregation does not hold. This results in a voter type model depending on four parameters; each of these parameters measures the strength of comp...

  6. Implicit vs explicit renormalization and effective interactions

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Arriola, E., E-mail: earriola@ugr.es [Departamento de Física Atómica, Molecular y Nuclear and Instituto Carlos I de Fisica Teórica y Computacional, Universidad de Granada, E-18071 Granada (Spain); Szpigel, S., E-mail: szpigel@mackenzie.br [Faculdade de Computação e Informática, Universidade Presbiteriana Mackenzie (Brazil); Timóteo, V.S., E-mail: varese@ft.unicamp.br [Grupo de Óptica e Modelagem Numérica – GOMNI, Faculdade de Tecnologia, Universidade Estadual de Campinas – UNICAMP (Brazil)

    2014-01-20

    Effective interactions can be obtained from a renormalization group analysis in two complementary ways. One can either explicitly integrate out higher energy modes or impose given conditions at low energies for a cut-off theory. While the first method is numerically involved, the second one can be solved almost analytically. In both cases we compare the outcoming effective interactions for the two nucleon system as functions of the cut-off scale and find a strikingly wide energy region where both approaches overlap, corresponding to relevant scales in light nuclei Λ≲200 MeV. This amounts to a great simplification in the determination of the effective interaction parameters.

  7. Evaluating the Free Energies of Solvation and Electronic Structures of Lithium-Ion Battery Electrolytes.

    Science.gov (United States)

    Shakourian-Fard, Mehdi; Kamath, Ganesh; Sankaranarayanan, Subramanian K R S

    2016-09-19

    Adaptive biasing force molecular dynamics simulations and density functional theory calculations were performed to understand the interaction of Li(+) with pure carbonates and ethylene carbonate (EC)-based binary mixtures. The most favorable Li carbonate cluster configurations obtained from molecular dynamics simulations were subjected to detailed structural and thermochemistry calculations on the basis of the M06-2X/6-311++G(d,p) level of theory. We report the ranking of these electrolytes on the basis of the free energies of Li-ion solvation in carbonates and EC-based mixtures. A strong local tetrahedral order involving four carbonates around the Li(+) was seen in the first solvation shell. Thermochemistry calculations revealed that the enthalpy of solvation and the Gibbs free energy of solvation of the Li(+) ion with carbonates are negative and suggested the ion-carbonate complexation process to be exothermic and spontaneous. Natural bond orbital analysis indicated that Li(+) interacts with the lone pairs of electrons on the carbonyl oxygen atom in the primary solvation sphere. These interactions lead to an increase in the carbonyl (C=O) bond lengths, as evidenced by a redshift in the vibrational frequencies [ν(C=O)] and a decrease in the electron density values at the C=O bond critical points in the primary solvation sphere. Quantum theory of atoms in molecules, localized molecular orbital energy decomposition analysis (LMO-EDA), and noncovalent interaction plots revealed the electrostatic nature of the Li(+) ion interactions with the carbonyl oxygen atoms in these complexes. On the basis of LMO-EDA, the strongest attractive interaction in these complexes was found to be the electrostatic interaction followed by polarization, dispersion, and exchange interactions. Overall, our calculations predicted EC and a binary mixture of EC/dimethyl carbonate to be appropriate electrolytes for Li-ion batteries, which complies with experiments and other theoretical results

  8. The effect of solvation on the radiation damage rate constants for adenine

    DEFF Research Database (Denmark)

    Milhøj, Birgitte Olai; Sauer, Stephan P. A.

    2016-01-01

    It is a well known fact, that water plays an important part in almost all biological systems and that inclusion of solvation effects might therefore be of utmost importance in studies of radiation damage to DNA. In the present investigation we have studied the effect of different solvation models...... in calculations of Gibbs free energies and reaction rates for the reaction between the OH radical and the DNA nucleobase adenine using Density Functional Theory at the ωB97X-D/6-311++G(2df,2pd) level with the Eckart tunneling correction. The solvent, water, has been included through either the implicit...

  9. Solvation thermodynamics of benzene, nitrobenzene, and aniline in water-acetonitrile mixtures

    Science.gov (United States)

    Antonova, O. A.; Smirnova, N. L.; Kustov, A. V.

    2017-09-01

    The enthalpies of dissolution of benzene, nitrobenzene, and aniline in water-acetonitrile mixtures are determined via calorimetry. The concentration dependences of the standard enthalpies of solvation of solutes are calculated. It is found that the concentration dependences of the standard enthalpies of solvation pass through maxima. The height of the observed maxima is shown to depend largely on the nature of the substituent. In the presence of a hydrophilic amino group capable of forming strong hydrogen bonds with water molecules, the value of a maximum falls; in the presence of a nitro group, it rises. The enthalpy parameters of pair interaction between molecules of water and benzene and its derivatives are calculated.

  10. Systems and methods for producing metal clusters; functionalized surfaces; and droplets including solvated metal ions

    Science.gov (United States)

    Cooks, Robert Graham; Li, Anyin; Luo, Qingjie

    2017-08-01

    The invention generally relates to systems and methods for producing metal clusters; functionalized surfaces; and droplets including solvated metal ions. In certain aspects, the invention provides methods that involve providing a metal and a solvent. The methods additionally involve applying voltage to the solvated metal to thereby produce solvent droplets including ions of the metal containing compound, and directing the solvent droplets including the metal ions to a target. In certain embodiments, once at the target, the metal ions can react directly or catalyze reactions.

  11. Modelos contínuos do solvente: fundamentos Continuum solvation models: fundamentals

    Directory of Open Access Journals (Sweden)

    Josefredo R. Pliego Jr

    2006-06-01

    Full Text Available Continuum solvation models are nowadays widely used in the modeling of solvent effects and the range of applications goes from the calculation of partition coefficients to chemical reactions in solution. The present work presents a detailed explanation of the physical foundations of continuum models. We discuss the polarization of a dielectric and its representation through the volume and surface polarization charges. The Poisson equation for a dielectric was obtained and we have also derived and discuss the apparent surface charge method and its application for free energy of solvation calculations.

  12. Angle-Resolved Photoemission of Solvated Electrons in Sodium-Doped Clusters.

    Science.gov (United States)

    West, Adam H C; Yoder, Bruce L; Luckhaus, David; Saak, Clara-Magdalena; Doppelbauer, Maximilian; Signorell, Ruth

    2015-04-16

    Angle-resolved photoelectron spectroscopy of the unpaired electron in sodium-doped water, methanol, ammonia, and dimethyl ether clusters is presented. The experimental observations and the complementary calculations are consistent with surface electrons for the cluster size range studied. Evidence against internally solvated electrons is provided by the photoelectron angular distribution. The trends in the ionization energies seem to be mainly determined by the degree of hydrogen bonding in the solvent and the solvation of the ion core. The onset ionization energies of water and methanol clusters do not level off at small cluster sizes but decrease slightly with increasing cluster size.

  13. Prediction of Henry's law constants of triazine derived herbicides from quantum chemical continuum solvation models.

    Science.gov (United States)

    Delgado, Eduardo J; Alderete, Joel B

    2003-01-01

    The Henry's law constants (H) for triazine derived herbicides are calculated using quantum chemical solvation models, SM2, SM3, PCM-DFT, and CPCM-DFT, and their performances are discussed. The results show considerable differences in performance among the different levels of theory. The values of H calculated by the semiempirical methods agree much better with the experimental values than those obtained at the DFT level. The differences are discussed in terms of the different contributions, electrostatic and no-electrostatic, to Gibbs free energy of solvation. In addition, the Henry's law constants of some triazine derived herbicides whose values have not been reported earlier are predicted as well.

  14. The emergence of explicit memory during learning.

    Science.gov (United States)

    Rose, Michael; Haider, Hilde; Büchel, Christian

    2010-12-01

    In incidental learning situations, contingencies are extracted from the environment without the intention to learn and can change behavior without awareness for the extracted regularity. The development of explicit access to the learned regularity is an important learning mechanism that is rarely examined. With a series of behavioral, electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) studies, we were able to show that the emergence of awareness for a hidden regularity is accompanied by an increase in neural activity and in high-frequency coupling between distant brain areas as observed with a time-frequency resolved EEG analysis. More importantly, the increase in neural coupling was observed before awareness for the learned material was established behaviorally. In addition, coupling increases were paralleled by an fMRI-signal increase in the ventral striatum and the right ventrolateral prefrontal cortex directly preceding the emergence of awareness. The involvement of this system, which has already been linked to the processing of predictions and prediction errors, indicates the relevance of a reinforcement signal to generate awareness for the learned contingencies. Thus, our data provide direct evidence for the necessity of large-scale coupling and the evaluation of a predictive stimulus value as the basis for a transition from implicit to explicit memory.

  15. Spatially explicit modelling of cholera epidemics

    Science.gov (United States)

    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.

  16. Does Sexually Explicit Media (SEM) Affect Me?

    DEFF Research Database (Denmark)

    Hald, Gert Martin; Træen, Bente; Noor, Syed W

    2015-01-01

    Using a self-selected online sample of 448 Norwegian men who have sex with men(MSM) and a cross-sectional design, the present study investigated first-person effectsof sexually explicit media (SEM) consumption on sexual knowledge, enjoyment of andinterest in sex, attitudes towards sex and underst......Using a self-selected online sample of 448 Norwegian men who have sex with men(MSM) and a cross-sectional design, the present study investigated first-person effectsof sexually explicit media (SEM) consumption on sexual knowledge, enjoyment of andinterest in sex, attitudes towards sex...... Scale (PCES). The study found that 93% of MSM reported smallto-largepositive effects from their SEM consumption on their sexual knowledge,enjoyment of and interest in sex, attitudes towards sex and understanding of theirsexual orientation. Only 7% reported any negative effects from their SEM...... consumptionon these outcomes. Furthermore, the psychometric properties of the revisedversion of the PCES were found to be very satisfactory. The results of the studyindicate that SEM consumption among MSM may play a positive role in MSM’ssexuality by enhancing their sex life, being a major source of sexual...

  17. DNA Release from Fe3+ -Cross-Linked Alginate Films Triggered by Logically Processed Biomolecular Signals: Integration of Biomolecular Computing and Actuation.

    Science.gov (United States)

    Gamella, Maria; Privman, Marina; Bakshi, Saira; Melman, Artem; Katz, Evgeny

    2017-07-05

    Signal-controlled release of DNA from Fe3+ -cross-linked alginate hydrogel electrochemically deposited on an electrode surface was studied. The multiple input signals were logically processed with the help of the enzyme-biocatalyzed reactions. Boolean logic gates, OR, AND, INH, were realized with the biocatalytic reactions performed by the enzymes entrapped in the alginate film. Hydrogen peroxide produced by the enzymatic reactions resulted in the degradation of the alginate hydrogel and DNA release. The alginate degradation was facilitated by the formation of free radicals in the Fenton-type reaction catalyzed by iron cations cross-linking the alginate hydrogel. The studied approach is versatile and can be adapted to various chemical signals processed by various enzymes with differently implemented Boolean logic. This work illustrates a novel concept of functional integration of biomolecular computing and actuation. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Vertical Electronic Excitations in Solution with the EOM-CCSD Method Combined with a Polarizable Explicit/Implicit Solvent Model.

    Science.gov (United States)

    Caricato, Marco; Lipparini, Filippo; Scalmani, Giovanni; Cappelli, Chiara; Barone, Vincenzo

    2013-07-09

    The accurate calculation of electronic transition energies and properties of isolated chromophores is not sufficient to provide a realistic simulation of their excited states in solution. In fact, the solvent influences the solute geometry, electronic structure, and response to external fields. Therefore, a proper description of the solvent effect is fundamental. This can be achieved by combining polarizable explicit and implicit representations of the solvent. The former provides a realistic description of solvent molecules around the solute, while the latter introduces the electrostatic effect of the bulk solution and reduces the need of too large a number of explicit solvent molecules. This strategy is particularly appealing when an accurate method such as equation of motion coupled cluster singles and doubles (EOM-CCSD) is employed for the treatment of the chromophore. In this contribution, we present the coupling of EOM-CCSD with a fluctuating charges (FQ) model and polarizable continuum model (PCM) of solvation for vertical excitations in a state-specific framework. The theory, implementation, and prototypical applications of the method are presented. Numerical tests on small solute-water clusters show very good agreement between full EOM-CCSD and EOM-CCSD-FQ calculations, with and without PCM, with differences ≤ 0.1 eV. Additionally, approximated schemes that further reduce the computational cost of the method are introduced and showed to perform well compared to the full method (errors ≤ 0.1 eV).

  19. Mechanisms for Solvatochromic Shifts of Free-Base Porphine Studied with Polarizable Continuum Models and Explicit Solute-Solvent Interactions.

    Science.gov (United States)

    Fukuda, Ryoichi; Ehara, Masahiro

    2013-01-08

    Solvatochromic shifts of free-base porphine in the Q-band and B-band were studied using the polarizable continuum model (PCM) and explicit solvent molecules employing time-dependent density functional theory (TDDFT) and the symmetry-adapted cluster-configuration interaction (SAC-CI) method. The state-specific (SS) and linear-response (LR) methods were examined in the PCM calculations. These models involve different types of solute-solvent interactions. The LR PCM and explicit solvation models reproduced the experimentally observed trends of the solvatochromic shifts, while the SS PCM failed to reproduce the experimental findings. The origin of the solvatochromic shifts of free-base porphine was dispersive interactions between the solute and solvent. Specific solute-solvent interactions would be important for a decrease of the splitting width between Q-bands. Based on the Casimir-Polder formula and a decomposition analysis, it was found that the dominant part of the solute-solvent interactions can be considered using independent particle approximations.

  20. A comparative study of explicit and implicit modelling of ...

    Indian Academy of Sciences (India)

    Further, for both speaker identification and verification tasks the explicit modelling provides relatively more complimentary information to the state-of-the-art vocal tract features. The contribution of the explicit features is relatively more robust against noise. We suggest that the explicit approach can be used to model the ...

  1. Simple and exact approach to the electronic polarization effect on the solvation free energy: formulation for quantum-mechanical/molecular-mechanical system and its applications to aqueous solutions.

    Science.gov (United States)

    Takahashi, Hideaki; Omi, Atsushi; Morita, Akihiro; Matubayasi, Nobuyuki

    2012-06-07

    We present a simple and exact numerical approach to compute the free energy contribution δμ in solvation due to the electron density polarization and fluctuation of a quantum-mechanical solute in the quantum-mechanical/molecular-mechanical (QM/MM) simulation combined with the theory of the energy representation (QM/MM-ER). Since the electron density fluctuation is responsible for the many-body QM-MM interactions, the standard version of the energy representation method cannot be applied directly. Instead of decomposing the QM-MM polarization energy into the pairwise additive and non-additive contributions, we take sum of the polarization energies in the QM-MM interaction and adopt it as a new energy coordinate for the method of energy representation. Then, it is demonstrated that the free energy δμ can be exactly formulated in terms of the energy distribution functions for the solution and reference systems with respect to this energy coordinate. The benchmark tests were performed to examine the numerical efficiency of the method with respect to the changes in the individual properties of the solvent and the solute. Explicitly, we computed the solvation free energy of a QM water molecule in ambient and supercritical water, and also the free-energy change associated with the isomerization reaction of glycine from neutral to zwitterionic structure in aqueous solution. In all the systems examined, it was demonstrated that the computed free energy δμ agrees with the experimental value, irrespective of the choice of the reference electron density of the QM solute. The present method was also applied to a prototype reaction of adenosine 5'-triphosphate hydrolysis where the effect of the electron density fluctuation is substantial due to the excess charge. It was demonstrated that the experimental free energy of the reaction has been accurately reproduced with the present approach.

  2. Fast isogeometric solvers for explicit dynamics

    KAUST Repository

    Gao, Longfei

    2014-06-01

    In finite element analysis, solving time-dependent partial differential equations with explicit time marching schemes requires repeatedly applying the inverse of the mass matrix. For mass matrices that can be expressed as tensor products of lower dimensional matrices, we present a direct method that has linear computational complexity, i.e., O(N), where N is the total number of degrees of freedom in the system. We refer to these matrices as separable matrices. For non-separable mass matrices, we present a preconditioned conjugate gradient method with carefully designed preconditioners as an alternative. We demonstrate that these preconditioners, which are easy to construct and cheap to apply (O(N)), can deliver significant convergence acceleration. The performances of these preconditioners are independent of the polynomial order (p independence) and mesh resolution (h independence) for maximum continuity B-splines, as verified by various numerical tests. © 2014 Elsevier B.V.

  3. [Explicit model for searching behavior of predator].

    Science.gov (United States)

    Tiutiunov, Iu V; Sapukhina, N Iu; Senina, I N; Arditi, R

    2002-01-01

    The authors present an approach for explicit modeling of spatio-temporal dynamics of predator-prey community. This approach is based on a reaction-diffusion-adjection PD (prey dependent) system. Local kinetics of population is determined by logistic reproduction function of prey, constant natural mortality of predator and Holling type 2 trophic function. Searching behavior of predator is described by the advective term in predator balance equation assuming the predator acceleration to be proportional to the prey density gradient. The model was studied with zero-flux boundary conditions. The influence of predator searching activity on the community dynamics, in particular, on the emergence of spatial heterogeneity, has been investigated by linear analysis and numerical simulations. It has been shown how searching activity may effect the persistence of species, stabilizing predator-prey interactions at very low level of pest density. It has been demonstrated that obtaining of such dynamic regimes does not require the use of complex trophic functions.

  4. Academic Publishing: Making the Implicit Explicit

    Directory of Open Access Journals (Sweden)

    Cecile Badenhorst

    2016-07-01

    Full Text Available For doctoral students, publishing in peer-reviewed journals is a task many face with anxiety and trepidation. The world of publishing, from choosing a journal, negotiating with editors and navigating reviewers’ responses is a bewildering place. Looking in from the outside, it seems that successful and productive academic writers have knowledge that is inaccessible to novice scholars. While there is a growing literature on writing for scholarly publication, many of these publications promote writing and publishing as a straightforward activity that anyone can achieve if they follow the rules. We argue that the specific and situated contexts in which academic writers negotiate publishing practices is more complicated and messy. In this paper, we attempt to make explicit our publishing processes to highlight the complex nature of publishing. We use autoethnographic narratives to provide discussion points and insights into the challenges of publishing peer reviewed articles. One narrative is by a doctoral student at the beginning of her publishing career, who expresses her desires, concerns and anxieties about writing for publication. The other narrative focuses on the publishing practices of a more experienced academic writer. Both are international scholars working in the Canadian context. The purpose of this paper is to explore academic publishing through the juxtaposition of these two narratives to make explicit some of the more implicit processes. Four themes emerge from these narratives. To publish successfully, academic writers need: (1 to be discourse analysts; (2 to have a critical competence; (3 to have writing fluency; and (4 to be emotionally intelligent.

  5. The Universal Statistical Distributions of the Affinity, Equilibrium Constants, Kinetics and Specificity in Biomolecular Recognition

    Science.gov (United States)

    Zheng, Xiliang; Wang, Jin

    2015-01-01

    We uncovered the universal statistical laws for the biomolecular recognition/binding process. We quantified the statistical energy landscapes for binding, from which we can characterize the distributions of the binding free energy (affinity), the equilibrium constants, the kinetics and the specificity by exploring the different ligands binding with a particular receptor. The results of the analytical studies are confirmed by the microscopic flexible docking simulations. The distribution of binding affinity is Gaussian around the mean and becomes exponential near the tail. The equilibrium constants of the binding follow a log-normal distribution around the mean and a power law distribution in the tail. The intrinsic specificity for biomolecular recognition measures the degree of discrimination of native versus non-native binding and the optimization of which becomes the maximization of the ratio of the free energy gap between the native state and the average of non-native states versus the roughness measured by the variance of the free energy landscape around its mean. The intrinsic specificity obeys a Gaussian distribution near the mean and an exponential distribution near the tail. Furthermore, the kinetics of binding follows a log-normal distribution near the mean and a power law distribution at the tail. Our study provides new insights into the statistical nature of thermodynamics, kinetics and function from different ligands binding with a specific receptor or equivalently specific ligand binding with different receptors. The elucidation of distributions of the kinetics and free energy has guiding roles in studying biomolecular recognition and function through small-molecule evolution and chemical genetics. PMID:25885453

  6. On the accuracy of one- and two-particle solvation entropies

    Science.gov (United States)

    Huggins, David J.

    2017-01-01

    Evaluating solvation entropies directly and combining with direct energy calculations is one way of calculating free energies of solvation and is used by Inhomogeneous Fluid Solvation Theory (IFST). The configurational entropy of a fluid is a function of the interatomic correlations and can thus be expressed in terms of correlation functions. The entropies in this work are directly calculated from a truncated series of integrals over these correlation functions. Many studies truncate all terms higher than the solvent-solute correlations. This study includes an additional solvent-solvent correlation term and assesses the associated free energy when IFST is applied to a fixed Lennard-Jones particle solvated in neon. The strength of the central potential is varied to imitate larger solutes. Average free energy estimates with both levels of IFST are able to reproduce the estimate made using the Free energy Perturbation (FEP) to within 0.16 kcal/mol. We find that the signal from the solvent-solvent correlations is very weak. Our conclusion is that for monatomic fluids simulated by pairwise classical potentials the correction term is relatively small in magnitude. This study shows it is possible to reproduce the free energy from a path based method like FEP, by only considering the endpoints of the path. This method can be directly applied to more complex solutes which break the spherical symmetry of this study. PMID:28527450

  7. Calculation of the free energy of solvation for neutral analogs of amino acid side chains

    NARCIS (Netherlands)

    Villa, Alessandra; Mark, AE

    2002-01-01

    The ability of the GROMOS96 force field to reproduce partition constants between water and two less polar solvents (cyclohexane and chloroform) for analogs of 18 of the 20 naturally occurring amino acids has been investigated. The estimations of the solvation free energies in water, in cyclohexane

  8. Ni(salen): a system that forms many solvates with interacting Ni atoms

    NARCIS (Netherlands)

    Siegler, M.A.M.|info:eu-repo/dai/nl/31411744X; Lutz, M.|info:eu-repo/dai/nl/304828971

    2009-01-01

    Recrystallization of [N,N’-Ethylene-bis(salicylideneiminato)]-nickel(II) [Ni(salen)] has been carried out from a large selection of solvents. Crystals can be either solvent free or solvates. This study is based on X-ray crystal structure determinations, which include the redetermination of Ni(salen)

  9. Solvated Positron Chemistry. Competitive Positron Reactions with Halide Ions in Water

    DEFF Research Database (Denmark)

    Christensen, Palle; Pedersen, Niels Jørgen; Andersen, J. R.

    1979-01-01

    It is shown by means of the angular correlation technique that the binding of positrons to halides is strongly influenced by solvation effects. For aqueous solutions we find increasing values for the binding energies between the halide and the positron with increasing mass of the halide. This is ....... This is contrary to the calculations of Cade and Farazdel for the vacuum case...

  10. Solvation phenomena in association theories with applications to oil & gas and chemical industries

    DEFF Research Database (Denmark)

    Kontogeorgis, Georgios; Folas, Georgios; Muro Sunè, Nuria

    2008-01-01

    with two non self-associating compounds may exhibit solvation specifically due to hydrogen bonding or more generally due to Lewis acid-Lewis base interactions. As examples can be mentioned mixtures with polar compounds (water, glycols...) and aromatic hydrocarbons and aqueous ether or ester solutions...

  11. Experimental and computational studies of polar solvation. Third year progress report, 1989--1991

    Energy Technology Data Exchange (ETDEWEB)

    1991-12-31

    Many articles and papers were published; a few are still in preparation or will be published. The solvation dynamics studies will be extended to ionic solutions. Computer simulations were also performed. A new line of research was begun on excited-state proton-transfer reactions catalyzed by alcohol solvents. (DLC)

  12. An application of the Miertus-Scrocco-Tomasi solvation model in molecular mechanics and dynamic simulations

    NARCIS (Netherlands)

    Varnek, A.A.; Wipff, G.; Glebov, A.S.; Feil, D.; Feil, D.

    1995-01-01

    The point-chart approximation of the Miertus-Scrocco-Tomasi solvation model (MST-PC) based on a continuum representation of the solvent has been incorporated in force field calculations. Application in molecular mechanics (MM) involves conformational equilibria in solution: rotational isomers of

  13. Trimethylamine-N-oxide's effect on polypeptide solvation at high pressure: a molecular dynamics simulation study.

    Science.gov (United States)

    Sarma, Rahul; Paul, Sandip

    2013-08-01

    The solvation characteristics of a 15-residue polypeptide and also the structure of the solution in the presence and absence of trimethylamine-N-oxide (TMAO), one of the strongest known protein stabilizers among the natural osmolytes both at low and high pressures, are investigated under high pressure conditions by employing the molecular dynamics simulation technique. The goal is to provide a molecular level understanding of how TMAO protects proteins at elevated pressures. Two different conformations of the polypeptide are used: helix and extended. Analysis of peptide hydration characteristics reveals that the pressure-induced enhancement of hydration number is higher for the extended state as compared to the helix. TMAO shows an opposite effect and causes more dehydration of the extended state. The total number of atomic sites that solvate peptide residues increases in the presence of TMAO, whereas the number of hydrogen bonds formed by peptide with solution species reduces due to the inability of TMAO to donate its hydrogen to peptide hydrogen bonding sites. In solution, both hydrophobic and hydrogen bonding sites of TMAO are found to be well solvated by water molecules and solvation of TMAO enhances water structure and reduces the number of nearest identical neighbors for water. Pressure and TMAO are seen to have counteracting effects on water structural properties. Implications of these results for counteracting mechanism of TMAO are discussed.

  14. Low solubility in drug development: de-convoluting the relative importance of solvation and crystal packing.

    Science.gov (United States)

    Docherty, Robert; Pencheva, Klimentina; Abramov, Yuriy A

    2015-06-01

    An increasing trend towards low solubility is a major issue for drug development as formulation of low solubility compounds can be problematic. This paper presents a model which de-convolutes the solubility of pharmaceutical compounds into solvation and packing properties with the intention to understand the solubility limiting features. The Cambridge Crystallographic Database was the source of structural information. Lattice energies were calculated via force-field based approaches using Materials Studio. The solvation energies were calculated applying quantum chemistry models using Cosmotherm software. The solubilities of 54 drug-like compounds were mapped onto a solvation energy/crystal packing grid. Four quadrants were identified were different balances of solvation and packing were defining the solubility. A version of the model was developed which allows for the calculation of the two features even in absence of crystal structure. Although there are significant number of in-silico models, it has been proven very difficult to predict aqueous solubility accurately. Therefore, we have taken a different approach where the solubility is not predicted directly but is de-convoluted into two constituent features. © 2015 Royal Pharmaceutical Society.

  15. Role of solvation structure in the shuttling of the hydrated excess ...

    Indian Academy of Sciences (India)

    RAJIB Biswas

    Marx D, Chandra A and Tuckerman M E 2010 Aqueous. Basic Solutions: Hydroxide Solvation, Structural Diffu- sion, and Comparison to the Hydrated Proton Chem. Rev. 110 2174. 36. Knight C, Maupin C M, Izvekov S and Voth G A 2010. Defining Condensed Phase Reactive Force Fields from ab Initio Molecular Dynamics ...

  16. Ab initio molecular dynamics of solvation effects on reactivity at electrified interfaces

    Science.gov (United States)

    Herron, Jeffrey A.; Morikawa, Yoshitada; Mavrikakis, Manos

    2016-08-01

    Using ab initio molecular dynamics as implemented in periodic, self-consistent (generalized gradient approximation Perdew-Burke-Ernzerhof) density functional theory, we investigated the mechanism of methanol electrooxidation on Pt(111). We investigated the role of water solvation and electrode potential on the energetics of the first proton transfer step, methanol electrooxidation to methoxy (CH3O) or hydroxymethyl (CH2OH). The results show that solvation weakens the adsorption of methoxy to uncharged Pt(111), whereas the binding energies of methanol and hydroxymethyl are not significantly affected. The free energies of activation for breaking the C-H and O-H bonds in methanol were calculated through a Blue Moon Ensemble using constrained ab initio molecular dynamics. Calculated barriers for these elementary steps on unsolvated, uncharged Pt(111) are similar to results for climbing-image nudged elastic band calculations from the literature. Water solvation reduces the barriers for both C-H and O-H bond activation steps with respect to their vapor-phase values, although the effect is more pronounced for C-H bond activation, due to less disruption of the hydrogen bond network. The calculated activation energy barriers show that breaking the C-H bond of methanol is more facile than the O-H bond on solvated negatively biased or uncharged Pt(111). However, with positive bias, O-H bond activation is enhanced, becoming slightly more facile than C-H bond activation.

  17. Effect of Higher Order Solvation and Temperature on SN2 and E2 Reactivity (Postprint)

    Science.gov (United States)

    2014-07-05

    trifluoride . Solvated ions, F(CH3OH)0–2, were produced by adding methanol to the source region of the instrument. Efforts were made to gently inject a...175. [2] J. Guo, et al., Microsolvation of the chlorine oxide anion and chlorine oxide radical: structures and energetics of the ClO(H2O)n and ClO

  18. Towards sensitive, high-throughput, biomolecular assays based on fluorescence lifetime

    Science.gov (United States)

    Ioanna Skilitsi, Anastasia; Turko, Timothé; Cianfarani, Damien; Barre, Sophie; Uhring, Wilfried; Hassiepen, Ulrich; Léonard, Jérémie

    2017-09-01

    Time-resolved fluorescence detection for robust sensing of biomolecular interactions is developed by implementing time-correlated single photon counting in high-throughput conditions. Droplet microfluidics is used as a promising platform for the very fast handling of low-volume samples. We illustrate the potential of this very sensitive and cost-effective technology in the context of an enzymatic activity assay based on fluorescently-labeled biomolecules. Fluorescence lifetime detection by time-correlated single photon counting is shown to enable reliable discrimination between positive and negative control samples at a throughput as high as several hundred samples per second.

  19. Biomolecular inflammatory response to surgical energy usage in laparoscopic surgery: results of a randomized study.

    Science.gov (United States)

    Agarwal, Brij B; Nanavati, Juhil D; Agarwal, Nayan; Sharma, Naveen; Agarwal, Krishna A; Manish, Kumar; Saluja, Satish; Agarwal, Sneh

    2016-05-01

    Use of surgical energy is integral to laparoscopic surgery (LS). Energized dissection (ED) has a potential to impact the biomolecular expression of inflammation due to ED-induced collateral inflammation. We did this triple-blind randomized controlled (RCT) study to assess this biomolecular footprint in an index LS, i.e., laparoscopic cholecystectomy (LC). This RCT was conducted in collaboration with tertiary-level institutions, from January 2014 to December 2014 with institutional review board clearance. Consecutive, unselected, consenting candidates for LC were randomized (after anesthesia induction) into group I (ED) and group II (non-ED). They were managed with compliance to universal protocols for ethics, informed consent, anesthesia, drug usage and clinical pathway with blinded observers. Biomolecular inflammatory markers, i.e., interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and highly sensitive CRP (HS-CRP), were measured with blood drawn juxta-preoperatively (H0), at 4 h (H4) and at 24 h (H24). The quantitative changes induced by ED on IL-6, TNF-α and HS-CRP at H0, H4 and H24 with their kinetic behavior were the study endpoint. Prospective data were analyzed statistically with a p value of biomolecular variables. There was a significant increase in IL-6, TNF-α and HS-CRP from H0 to H4 in both the groups (p values <0.001). From H4 to H24, all three cytokines showed significant increase in ED group (p < 0.05), whereas in the non-ED group, IL-6 showed significant fall (p = 0.004) and TNF-α showed no significant change (p = 0.063). Both the groups showed H4-H24 elevation of HS-CRP (p = 0.000). Energized dissection adds to the cytokine-mediated postoperative inflammation. The additional ED-induced inflammation can be measured objectively by IL-6 and TNF-α levels. Clinical Trials Registry, India (REF/2014/06/007153).

  20. Force sensors based on piezoresistive and MOSFET cantilevers for biomolecular sensing

    OpenAIRE

    Tosolini, Giordano

    2013-01-01

    Los procesos de reconocimiento biomolecular entre receptores y ligandos son muy importantes en biología. Estas biomoléculas pueden desarrollar complejos muy específicos y tener una variedad de funciones como replicación y transcripción genómica, actividad enzimática, respuesta inmune, señalamiento celular, etc. La complementariedad inequívoca mostrada por estos componentes biológicos es ampliamente utilizada para desarrollar biosensores. Dependiendo de la naturaleza de las señales que se conv...

  1. In situ monitoring of biomolecular processes in living systems using surface-enhanced Raman scattering

    Science.gov (United States)

    Altunbek, Mine; Kelestemur, Seda; Culha, Mustafa

    2015-12-01

    Surface-enhanced Raman scattering (SERS) continues to strive to gather molecular level information from dynamic biological systems. It is our ongoing effort to utilize the technique for understanding of the biomolecular processes in living systems such as eukaryotic and prokaryotic cells. In this study, the technique is investigated to identify cell death mechanisms in 2D and 3D in vitro cell culture models, which is a very important process in tissue engineering and pharmaceutical applications. Second, in situ biofilm formation monitoring is investigated to understand how microorganisms respond to the environmental stimuli, which inferred information can be used to interfere with biofilm formation and fight against their pathogenic activity.

  2. Cell-free extract based optimization of biomolecular circuits with droplet microfluidics.

    Science.gov (United States)

    Hori, Yutaka; Kantak, Chaitanya; Murray, Richard M; Abate, Adam R

    2017-09-12

    Engineering an efficient biomolecular circuit often requires time-consuming iterations of optimization. Cell-free protein expression systems allow rapid testing of biocircuits in vitro, speeding the design-build-test cycle of synthetic biology. In this paper, we combine this with droplet microfluidics to densely scan a transcription-translation biocircuit space. Our system assays millions of parameter combinations per hour, providing a detailed map of function. The ability to comprehensively map biocircuit parameter spaces allows accurate modeling to predict circuit function and identify optimal circuits and conditions.

  3. An optics-based variable-temperature assay system for characterizing thermodynamics of biomolecular reactions on solid support

    Energy Technology Data Exchange (ETDEWEB)

    Fei, Yiyan; Landry, James P.; Zhu, X. D., E-mail: xdzhu@physics.ucdavis.edu [Department of Physics, University of California, One Shields Avenue, Davis, California 95616 (United States); Li, Yanhong; Yu, Hai; Lau, Kam; Huang, Shengshu; Chokhawala, Harshal A.; Chen, Xi [Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616 (United States)

    2013-11-15

    A biological state is equilibrium of multiple concurrent biomolecular reactions. The relative importance of these reactions depends on physiological temperature typically between 10 °C and 50 °C. Experimentally the temperature dependence of binding reaction constants reveals thermodynamics and thus details of these biomolecular processes. We developed a variable-temperature opto-fluidic system for real-time measurement of multiple (400–10 000) biomolecular binding reactions on solid supports from 10 °C to 60 °C within ±0.1 °C. We illustrate the performance of this system with investigation of binding reactions of plant lectins (carbohydrate-binding proteins) with 24 synthetic glycans (i.e., carbohydrates). We found that the lectin-glycan reactions in general can be enthalpy-driven, entropy-driven, or both, and water molecules play critical roles in the thermodynamics of these reactions.

  4. Characterization of organic electrolyte systems by nuclear magnetic resonance and molecular orbital simulation: equilibrium constant and net charge distribution in solvation state

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Juichi; Nishimura, Katsunori; Muranaka, Yasushi; Ito, Yutaka [Hitachi Ltd., Ibaraki (Japan). Res. Lab.

    1997-10-01

    Solvation states of single solvent electrolyte systems of ethylene carbonate (EC), propylene carbonate (PC), dimethyl carbonate (DMC), ethylmethyl carbonate (EMC) and diethyl carbonate (DEC) with LiPF{sub 6} were characterized by {sup 13}C-NMR solvation shift and molecular orbital (MO) simulation. Dissociation constants and solvation constants were estimated by parameter fitting to solvation shift using a simple equilibrium model. The solvation shifts {Delta}{delta} were observed not only at a lower field but also at a higher field due to change of net charge {Delta}{rho} in solvent molecules by Li{sup +} attachment. This particular feature of solvation shifts was demonstrated in the molecular orbital simulation as driven by the change of net charge using a 1:1 (Li{sup +}:solvent) solvation model. (orig.)

  5. Characterization of organic electrolyte systems by nuclear magnetic resonance and molecular orbital simulation: Equilibrium constant and net charge distribution in solvation state

    Science.gov (United States)

    Arai, Juichi; Nishimura, Katsunori; Muranaka, Yasushi; Ito, Yutaka

    Solvation states of single solvent electrolyte systems of ethylene carbonate (EC), propylene carbonate (PC), dimethyl carbonate (DMC), ehylmethyl carbonate (EMC) and diethyl carbonate (DEC) with LiPF 6 were characterized by 13C-NMR solvation shift and molecular orbital (MO) simulation. Dissociation constants and solvation constants were estimated by parameter fitting to solvation shift using a simple equilibrium model. The solvation shifts Δδ were observed not only at a lower field but also at a higher field due to change of net charge Δ ρ in solvent molecules by Li + attachment. This particular feature of solvation shifts was demonstrated in the molecular orbital simulation as driven by the change of net charge using a 1:1 (Li +:solvent) solvation model.

  6. Competitive Lithium Solvation of Linear and Cyclic Carbonates from Quantum Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Borodin, Oleg; Olguin, Marco; Ganesh, P.; Kent, Paul; Allen, Joshua S.; Henderson, Wesley A.

    2015-11-17

    The composition of the lithium cation (Li+) solvation shell in mixed linear and cyclic carbonate-based electrolytes has been re-examined using Born–Oppenheimer molecular dynamics (BOMD) as a function of salt concentration with ethylene carbonate:dimethyl carbonate (EC:DMC)-LiPF6 as a model system. A slight coordination preference for EC over DMC to a Li+ was found at low salt concentrations, while a slightly higher preference for DMC over EC was found at high salt concentrations. Analysis of the relative binding energies of the (EC)n(DMC)m-Li+ and (EC)n(DMC)m-LiPF6 solvates in the gas-phase and for an implicit solvent (as a function of the solvent dielectric constant) indicated that the DMC-containing Li+ solvates were stabilized relative to (EC4)-Li+ and (EC)3-LiPF6 by immersing them in the implicit solvent. Such stabilization was more pronounced in the implicit solvents with a high dielectric constant. Results from previous Raman and IR experiments were reanalyzed and reconciled by correcting them for changes of the Raman activities, IR intensities and band shifts for the solvents which occur upon Li+ coordination. After these correction factors were applied to the results of BOMD simulations, the composition of the Li+ solvation shell from the BOMD simulations was found to agree well with the solvation numbers extracted from Raman experiments. Finally, the mechanism of the Li+ diffusion in the (EC:DMC)LiPF6 mixed solvent electrolyte was studied using the BOMD simulations.

  7. Deciphering the photochemical mechanisms describing the UV-induced processes occurring in solvated guanine monophosphate

    Directory of Open Access Journals (Sweden)

    Salvatore Flavio Altavilla

    2015-04-01

    Full Text Available The photophysics and photochemistry of water-solvated guanine monophosphate (GMP are here characterized by means of a multireference quantum-chemical/molecular mechanics theoretical approach (CASPT2//CASSCF/AMBER in order to elucidate the main photo-processes occurring upon UV-light irradiation. The effect of the solvent and of the phosphate group on the energetics and structural features of this system are evaluated for the first time employing high-level ab initio methods and thoroughly compared to those in vacuo previously reported in the literature and to the experimental evidence to assess to which extent they influence the photoinduced mechanisms. Solvated electronic excitation energies of solvated GMP at the Franck-Condon (FC region show a red shift for the ππ* La and Lb states, whereas the energy of the oxygen lone-pair nπ* state is blue-shifted. The main photoinduced decay route is promoted through a ring-puckering motion along the bright lowest-lying La state towards a conical intersection (CI with the ground state, involving a very shallow stationary point along the minimum energy pathway in contrast to the barrierless profile found in gas-phase, the point being placed at the end of the minimum energy path (MEP thus endorsing its ultrafast deactivation in accordance with time-resolved transient and photoelectron spectroscopy experiments. The role of the nπ* state in the solvated system is severely diminished as the crossings with the initially populated La state and also with the Lb state are placed too high energetically to partake prominently in the deactivation photo-process. The proposed mechanism present in solvated and in vacuo DNA/RNA chromophores validates the intrinsic photostability mechanism through CI-mediated non-radiative processes accompanying the bright excited-state population towards the ground state and subsequent relaxation back to the FC region.

  8. Deciphering the photochemical mechanisms describing the UV-induced processes occurring in solvated guanine monophosphate

    Science.gov (United States)

    Altavilla, Salvatore; Segarra-Martí, Javier; Nenov, Artur; Conti, Irene; Rivalta, Ivan; Garavelli, Marco

    2015-04-01

    The photophysics and photochemistry of water-solvated guanine monophosphate (GMP) are here characterized by means of a multireference quantum-chemical/molecular mechanics theoretical approach (CASPT2//CASSCF/AMBER) in order to elucidate the main photo-processes occurring upon UV-light irradiation. The effect of the solvent and of the phosphate group on the energetics and structural features of this system are evaluated for the first time employing high-level ab initio methods and thoroughly compared to those in vacuo previously reported in the literature and to the experimental evidence to assess to which extent they influence the photoinduced mechanisms. Solvated electronic excitation energies of solvated GMP at the Franck-Condon (FC) region show a red shift for the ππ* La and Lb states, whereas the energy of the oxygen lone-pair nπ* state is blue-shifted. The main photoinduced decay route is promoted through a ring-puckering motion along the bright lowest-lying La state towards a conical intersection (CI) with the ground state, involving a very shallow stationary point along the minimum energy pathway in contrast to the barrierless profile found in gas-phase, the point being placed at the end of the minimum energy path (MEP) thus endorsing its ultrafast deactivation in accordance with time-resolved transient and photoelectron spectroscopy experiments. The role of the nπ* state in the solvated system is severely diminished as the crossings with the initially populated La state and also with the Lb state are placed too high energetically to partake prominently in the deactivation photo-process. The proposed mechanism present in solvated and in vacuo DNA/RNA chromophores validates the intrinsic photostability mechanism through CI-mediated non-radiative processes accompanying the bright excited-state population towards the ground state and subsequent relaxation back to the FC region.

  9. Enhanced on-chip SERS based biomolecular detection using electrokinetically active microwells.

    Science.gov (United States)

    Huh, Yun Suk; Chung, Aram J; Cordovez, Bernardo; Erickson, David

    2009-02-07

    Here we present a novel microfluidic technique for on-chip surface enhanced Raman spectroscopy (SERS) based biomolecular detection, exploiting the use of electrokinetically active microwells. Briefly, the chip comprises of a series of microfluidic channels containing embedded microwells that, when electrically actuated, either locally attract or repulse species from solution through a combination of electrokinetic effects. We demonstrate that the approach combines the advantages of existing homogeneous (solution phase) and heterogeneous (surface phase) on-chip techniques by enabling active mixing to enhance the rate of binding between the SERS enhancers and the biomolecular targets as well as rapid concentration of the product for surface phase optical interrogation. This paper describes the chip design and fabrication procedure, experimental results illustrating the optimal conditions for our concentration and mixing processes, and a numerical analysis of the flow pattern. To demonstrate the usefulness of the device we apply it to the quantitative detection of nucleic acid sequences associated with Dengue virus serotype 2. We report a limit of detection for Dengue sequences of 30 pM and show excellent specificity against other serotypes.

  10. Biomolecular stiffness detection based on positive frequency shift of CMOS compatible gigahertz solidly mounted resonators.

    Science.gov (United States)

    Yang, Qingrui; Pan, Shuting; Zhao, Yuan; Zhang, Hao; Pang, Wei; Duan, Xuexin

    2017-10-15

    In this work, gigahertz solidly mounted resonators (SMRs) (2.5GHz) were designed and fabricated to construct a novel particle-resonator system to achieve the biomolecular stiffness sensing in real time. The positive frequency shift of the system was used to estimate the stiffness of biomolecules connecting between the SMR and attached particles. The working principle was revealed by the mathematical analysis of the general block-spring model of the system. Further interpretations about the mechanism of such elastic interaction from the perspective of acoustic resonant modes of SMRs were given by finite element method. Biotin-streptavidin, antibody and antigen binding system were used as model molecular linkers to study the frequency shift varied with different particle diameters and particle densities. Different linker stiffness was realized by adjusting the concentrations of antigens connected with particles which form specific binding with antibodies immobilized on the SMR. The results fairly agree with the simulation results demonstrating the proposed particle-resonator system as an effective method to realize the real-time biomolecular stiffness detection. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Conformation of bovine submaxillary mucin layers on hydrophobic surface as studied by biomolecular probes.

    Science.gov (United States)

    Pakkanen, Kirsi I; Madsen, Jan B; Lee, Seunghwan

    2015-01-01

    In the present study, the conformational changes of bovine submaxillary mucin (BSM) adsorbed on a hydrophobic surface (polystyrene (PS)) as a function of concentration in bulk solution (up to 2mg/mL) have been investigated with biomolecular probe-based approaches, including bicinchoninic acid (BCA), enzyme-linked immunosorbent assay (EIA), and enzyme-linked lectin assay (ELLA). The conformation and hydrodynamic diameter of highly purified BSM molecules, as characterized by circular dichroism (CD) spectroscopy and dynamic light scattering (DLS), respectively, showed a slight, yet gradual coiling and compaction in response to the increase in BSM concentration in bulk solution. Adsorbed masses of BSM onto hydrophobic surface, as probe by BCA, showed a continuously increasing trend up to 2mg/mL. But, the signals from EIA and ELLA, which probe the concentration of available unglycosylated C-terminals and the central glycosylated regions, respectively, showed complicated non-linear responses with increasing surface concentration. The results from this study support the conventional amphiphilic, triblock model of BSM in the adsorption onto hydrophobic surface from aqueous solution. The biomolecular probe-based approaches employed in this study, however, provided further details on the conformational changes of BSM on surface, in particular the accessibility of glycosylated and unglycosylated domains with increasing surface concentration. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. The HADDOCK2.2 Web Server: User-Friendly Integrative Modeling of Biomolecular Complexes.

    Science.gov (United States)

    van Zundert, G C P; Rodrigues, J P G L M; Trellet, M; Schmitz, C; Kastritis, P L; Karaca, E; Melquiond, A S J; van Dijk, M; de Vries, S J; Bonvin, A M J J

    2016-02-22

    The prediction of the quaternary structure of biomolecular macromolecules is of paramount importance for fundamental understanding of cellular processes and drug design. In the era of integrative structural biology, one way of increasing the accuracy of modeling methods used to predict the structure of biomolecular complexes is to include as much experimental or predictive information as possible in the process. This has been at the core of our information-driven docking approach HADDOCK. We present here the updated version 2.2 of the HADDOCK portal, which offers new features such as support for mixed molecule types, additional experimental restraints and improved protocols, all of this in a user-friendly interface. With well over 6000 registered users and 108,000 jobs served, an increasing fraction of which on grid resources, we hope that this timely upgrade will help the community to solve important biological questions and further advance the field. The HADDOCK2.2 Web server is freely accessible to non-profit users at http://haddock.science.uu.nl/services/HADDOCK2.2. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Application of Frontal Affinity Chromatography to Study the Biomolecular Interactions with Trypsin.

    Science.gov (United States)

    Hu, YuanYuan; Qian, Junqing; Guo, Hui; Jiang, ShengLan; Zhang, Zheng

    2015-07-01

    Trypsin is a serine protease that has been proposed as a potential therapeutic target for metabolic disorders and malignancy diseases, thus the identification of biomolecular interactions of compounds to trypsin could be of great therapeutic importance. In this study, trypsin was immobilized on a monolithic silica capillary column via sol-gel. The binding properties of four small molecules (daidzin, genistin, matrine and oxymatrine) to trypsin were examined using the trypsin affinity columns by frontal analysis. The results indicate that the matrine (dissociation constant, Kd = 7.904 μM) has stronger interaction with trypsin than the oxymatrine (Kd = 8.204 μM), whereas daidzin and genistin were nearly have no affinity with trypsin. The results demonstrated that the frontal affinity chromatography can be used for the direct determination of protein-protease inhibitor binding interactions and have several significant advantages, including easy fabricating, reproducible, minimal technological requirements and potential to become a reliable alternative for quantitative studies of biomolecular interactions. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Extracting intrinsic dynamic parameters of biomolecular folding from single-molecule force spectroscopy experiments.

    Science.gov (United States)

    Nam, Gi-Moon; Makarov, Dmitrii E

    2016-01-01

    Single-molecule studies in which a mechanical force is transmitted to the molecule of interest and the molecular extension or position is monitored as a function of time are versatile tools for probing the dynamics of protein folding, stepping of molecular motors, and other biomolecular processes involving activated barrier crossing. One complication in interpreting such studies, however, is the fact that the typical size of a force probe (e.g., a dielectric bead in optical tweezers or the atomic force microscope tip/cantilever assembly) is much larger than the molecule itself, and so the observed molecular motion is affected by the hydrodynamic drag on the probe. This presents the experimenter with a nontrivial task of deconvolving the intrinsic molecular parameters, such as the intrinsic free energy barrier and the effective diffusion coefficient exhibited while crossing the barrier from the experimental signal. Here we focus on the dynamical aspect of this task and show how the intrinsic diffusion coefficient along the molecular reaction coordinate can be inferred from single-molecule measurements of the rates of biomolecular folding and unfolding. We show that the feasibility of accomplishing this task is strongly dependent on the relationship between the intrinsic molecular elasticity and that of the linker connecting the molecule to the force probe and identify the optimal range of instrumental parameters allowing determination of instrument-free molecular dynamics. © 2015 The Protein Society.

  15. Biomolecular detection at ssDNA-conjugated nanoparticles by nano-impact electrochemistry.

    Science.gov (United States)

    Karimi, Anahita; Hayat, Akhtar; Andreescu, Silvana

    2017-01-15

    We describe the use of ssDNA functionalized silver nanoparticle (AgNP) probes for quantitative investigation of biorecognition and real time detection of biomolecular targets using nano-impact electrochemistry. The method is based on measurements of the individual collision events between ssDNA aptamer-functionalized AgNPs and a carbon fiber miroelectrode (CFME). Specific binding events of target analyte induced collision frequency changes enabling ultrasensitive detection of the aptamer target in a single step. These changes are assigned to the surface coverage of the NP by the ssDNA aptamers and subsequent conformational changes of the aptamer probe which affect the electron transfer between the NP and the electrode surface. The method enables sensitive and selective detection of ochratoxin A (OTA), chosen here as a model target, with a limit of detection of 0.05nM and a relative standard deviation of 4.9%. The study provides a means of characterizing bioconjugation of AgNPs with aptamers and assessing biomolecular recognition events with high sensitivity and without the use of exogenous reagents or enzyme amplification steps. This methodology can be broadly applicable to other bioconjugated systems, biosensing and related bioanalytical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Single-molecule imaging and manipulation of biomolecular machines and systems.

    Science.gov (United States)

    Iino, Ryota; Iida, Tatsuya; Nakamura, Akihiko; Saita, Ei-Ichiro; You, Huijuan; Sako, Yasushi

    2018-02-01

    Biological molecular machines support various activities and behaviors of cells, such as energy production, signal transduction, growth, differentiation, and migration. We provide an overview of single-molecule imaging methods involving both small and large probes used to monitor the dynamic motions of molecular machines in vitro (purified proteins) and in living cells, and single-molecule manipulation methods used to measure the forces, mechanical properties and responses of biomolecules. We also introduce several examples of single-molecule analysis, focusing primarily on motor proteins and signal transduction systems. Single-molecule analysis is a powerful approach to unveil the operational mechanisms both of individual molecular machines and of systems consisting of many molecular machines. Quantitative, high-resolution single-molecule analyses of biomolecular systems at the various hierarchies of life will help to answer our fundamental question: "What is life?" This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. The generation of biomolecular patterns in highly porous collagen-GAG scaffolds using direct photolithography.

    Science.gov (United States)

    Martin, Teresa A; Caliari, Steven R; Williford, Paul D; Harley, Brendan A; Bailey, Ryan C

    2011-06-01

    The extracellular matrix (ECM) is a complex organization of structural proteins found within tissues and organs. Heterogeneous tissues with spatially and temporally modulated properties play an important role in organism physiology. Here we present a benzophenone (BP) based direct, photolithographic approach to spatially pattern solution phase biomolecules within collagen-GAG (CG) scaffolds and demonstrate creation of a wide range of patterns composed of multiple biomolecular species in a manner independent from scaffold fabrication steps. We demonstrate the ability to immobilize biomolecules at surface densities of up to 1000 ligands per square micron on the scaffold strut surface and to depths limited by the penetration depth of the excitation source into the scaffold structure. Importantly, while BP photopatterning does further crosslink the CG scaffold, evidenced by increased mechanical properties and collagen crystallinity, it does not affect scaffold microstructural or compositional properties or negatively influence cell adhesion, viability, or proliferation. We show that covalently photoimmobilized fibronectin within a CG scaffold significantly increases the speed of MC3T3-E1 cell attachment relative to the bare CG scaffold or non-specifically adsorbed fibronectin, suggesting that this approach can be used to improve scaffold bioactivity. Our findings, on the whole, establish the use of direct, BP photolithography as a methodology for covalently incorporating activity-improving biochemical cues within 3D collagen biomaterial scaffolds with spatial control over biomolecular deposition. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Investigating biomolecular recognition at the cell surface using atomic force microscopy.

    Science.gov (United States)

    Wang, Congzhou; Yadavalli, Vamsi K

    2014-05-01

    Probing the interaction forces that drive biomolecular recognition on cell surfaces is essential for understanding diverse biological processes. Force spectroscopy has been a widely used dynamic analytical technique, allowing measurement of such interactions at the molecular and cellular level. The capabilities of working under near physiological environments, combined with excellent force and lateral resolution make atomic force microscopy (AFM)-based force spectroscopy a powerful approach to measure biomolecular interaction forces not only on non-biological substrates, but also on soft, dynamic cell surfaces. Over the last few years, AFM-based force spectroscopy has provided biophysical insight into how biomolecules on cell surfaces interact with each other and induce relevant biological processes. In this review, we focus on describing the technique of force spectroscopy using the AFM, specifically in the context of probing cell surfaces. We summarize recent progress in understanding the recognition and interactions between macromolecules that may be found at cell surfaces from a force spectroscopy perspective. We further discuss the challenges and future prospects of the application of this versatile technique. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. ISAMBARD: an open-source computational environment for biomolecular analysis, modelling and design.

    Science.gov (United States)

    Wood, Christopher W; Heal, Jack W; Thomson, Andrew R; Bartlett, Gail J; Ibarra, Amaurys Á; Brady, R Leo; Sessions, Richard B; Woolfson, Derek N

    2017-10-01

    The rational design of biomolecules is becoming a reality. However, further computational tools are needed to facilitate and accelerate this, and to make it accessible to more users. Here we introduce ISAMBARD, a tool for structural analysis, model building and rational design of biomolecules. ISAMBARD is open-source, modular, computationally scalable and intuitive to use. These features allow non-experts to explore biomolecular design in silico. ISAMBARD addresses a standing issue in protein design, namely, how to introduce backbone variability in a controlled manner. This is achieved through the generalization of tools for parametric modelling, describing the overall shape of proteins geometrically, and without input from experimentally determined structures. This will allow backbone conformations for entire folds and assemblies not observed in nature to be generated de novo, that is, to access the 'dark matter of protein-fold space'. We anticipate that ISAMBARD will find broad applications in biomolecular design, biotechnology and synthetic biology. A current stable build can be downloaded from the python package index (https://pypi.python.org/pypi/isambard/) with development builds available on GitHub (https://github.com/woolfson-group/) along with documentation, tutorial material and all the scripts used to generate the data described in this paper. d.n.woolfson@bristol.ac.uk or chris.wood@bristol.ac.uk. Supplementary data are available at Bioinformatics online.

  20. Time-resolved methods in biophysics. 9. Laser temperature-jump methods for investigating biomolecular dynamics.

    Science.gov (United States)

    Kubelka, Jan

    2009-04-01

    Many important biochemical processes occur on the time-scales of nanoseconds and microseconds. The introduction of the laser temperature-jump (T-jump) to biophysics more than a decade ago opened these previously inaccessible time regimes up to direct experimental observation. Since then, laser T-jump methodology has evolved into one of the most versatile and generally applicable methods for studying fast biomolecular kinetics. This perspective is a review of the principles and applications of the laser T-jump technique in biophysics. A brief overview of the T-jump relaxation kinetics and the historical development of laser T-jump methodology is presented. The physical principles and practical experimental considerations that are important for the design of the laser T-jump experiments are summarized. These include the Raman conversion for generating heating pulses, considerations of size, duration and uniformity of the temperature jump, as well as potential adverse effects due to photo-acoustic waves, cavitation and thermal lensing, and their elimination. The laser T-jump apparatus developed at the NIH Laboratory of Chemical Physics is described in detail along with a brief survey of other laser T-jump designs in use today. Finally, applications of the laser T-jump in biophysics are reviewed, with an emphasis on the broad range of problems where the laser T-jump methodology has provided important new results and insights into the dynamics of the biomolecular processes.

  1. Technology Development of Miniaturized Far-Infrared Sources for Biomolecular Spectroscopy

    Science.gov (United States)

    Kono, Junichiro

    2003-01-01

    The objective of this project was to develop a purely solid-state based, thus miniaturized, far-infrared (FIR) (also known as terahertz (THz)) wave source using III-V semiconductor nanostructures for biomolecular detection and sensing. Many biomolecules, such as DNA and proteins, have distinct spectroscopic features in the FIR wavelength range as a result of vibration-rotation-tunneling motions and various inter- and intra-molecule collective motions. Spectroscopic characterization of such molecules requires narrow linewidth, sufficiently high power, tunable (in wavelength), and coherent FIR sources. Unfortunately, the FIR frequency is one of the least technologically developed ranges in the electromagnetic spectrum. Currently available FIR sources based on non-solid state technology are bulky, inefficient, and very often incoherent. In this project we investigated antimonide based compound semiconductor (ABCS) nanostructures as the active medium to generate FIR radiation. The final goal of this project was to demonstrate a semiconductor THz source integrated with a pumping diode laser module to achieve a compact system for biomolecular applications.

  2. Photochemical functionalization of gallium nitride thin films with molecular and biomolecular layers.

    Science.gov (United States)

    Kim, Heesuk; Colavita, Paula E; Metz, Kevin M; Nichols, Beth M; Sun, Bin; Uhlrich, John; Wang, Xiaoyu; Kuech, Thomas F; Hamers, Robert J

    2006-09-12

    We demonstrate that photochemical functionalization can be used to functionalize and photopattern the surface of gallium nitride crystalline thin films with well-defined molecular and biomolecular layers. GaN(0001) surfaces exposed to a hydrogen plasma will react with organic molecules bearing an alkene (C=C) group when illuminated with 254 nm light. Using a bifunctional molecule with an alkene group at one end and a protected amine group at the other, this process can be used to link the alkene group to the surface, leaving the protected amine exposed. Using a simple contact mask, we demonstrate the ability to directly pattern the spatial distribution of these protected amine groups on the surface with a lateral resolution of <12 mum. After deprotection of the amines, single-stranded DNA oligonucleotides were linked to the surface using a bifunctional cross-linker. Measurements using fluorescently labeled complementary and noncomplementary sequences show that the DNA-modified GaN surfaces exhibit excellent selectivity, while repeated cycles of hybridization and denaturation in urea show good stability. These results demonstrate that photochemical functionalization can be used as an attractive starting point for interfacing molecular and biomolecular systems with GaN and other compound semiconductors.

  3. Elastic network models for understanding biomolecular machinery: from enzymes to supramolecular assemblies

    Science.gov (United States)

    Chennubhotla, Chakra; Rader, A. J.; Yang, Lee-Wei; Bahar, Ivet

    2005-12-01

    With advances in structure genomics, it is now recognized that knowledge of structure alone is insufficient to understand and control the mechanisms of biomolecular function. Additional information in the form of dynamics is needed. As demonstrated in a large number of studies, the machinery of proteins and their complexes can be understood to a good approximation by adopting Gaussian (or elastic) network models (GNM) for simplified normal mode analyses. While this approximation lacks chemical details, it provides us with a means for assessing the collective motions of large structures/assemblies and perform a comparative analysis of a series of proteins, thus providing insights into the mechanical aspects of biomolecular dynamics. In this paper, we discuss recent applications of GNM to a series of enzymes as well as large structures such as the HK97 bacteriophage viral capsids. Understanding the dynamics of large protein structures can be computationally challenging. To this end, we introduce a new approach for building a hierarchical, reduced rank representation of the protein topology and consequently the fluctuation dynamics.

  4. The interplay of intrinsic and extrinsic bounded noises in biomolecular networks.

    Directory of Open Access Journals (Sweden)

    Giulio Caravagna

    Full Text Available After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a biomolecular network. The influence of intrinsic and extrinsic noises on biomolecular networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: (i the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, (ii a model of enzymatic futile cycle and (iii a genetic toggle switch. In (ii and (iii we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possible functional role of bounded noises.

  5. DockScreen: A Database of In Silico Biomolecular Interactions to Support Computational Toxicology

    Directory of Open Access Journals (Sweden)

    Michael-Rock Goldsmith

    2014-01-01

    Full Text Available We have developed DockScreen, a database of in silico biomolecular interactions designed to enable rational molecular toxicological insight within a computational toxicology framework. This database is composed of chemical/target (receptor and enzyme binding scores calculated by molecular docking of more than 1000 chemicals into 150 protein targets and contains nearly 135 thousand unique ligand/target binding scores. Obtaining this dataset was achieved using eHiTS (Simbiosys Inc., a fragment-based molecular docking approach with an exhaustive search algorithm, on a heterogeneous distributed high-performance computing framework. The chemical landscape covered in DockScreen comprises selected environmental and therapeutic chemicals. The target landscape covered in DockScreen was selected based on the availability of high-quality crystal structures that covered the assay space of phase I ToxCast in vitro assays. This in silico data provides continuous information that establishes a means for quantitatively comparing, on a structural biophysical basis, a chemical’s profile of biomolecular interactions. The combined minimum-score chemical/target matrix is provided.

  6. Spatially explicit dynamic N-mixture models

    Science.gov (United States)

    Zhao, Qing; Royle, Andy; Boomer, G. Scott

    2017-01-01

    Knowledge of demographic parameters such as survival, reproduction, emigration, and immigration is essential to understand metapopulation dynamics. Traditionally the estimation of these demographic parameters requires intensive data from marked animals. The development of dynamic N-mixture models makes it possible to estimate demographic parameters from count data of unmarked animals, but the original dynamic N-mixture model does not distinguish emigration and immigration from survival and reproduction, limiting its ability to explain important metapopulation processes such as movement among local populations. In this study we developed a spatially explicit dynamic N-mixture model that estimates survival, reproduction, emigration, local population size, and detection probability from count data under the assumption that movement only occurs among adjacent habitat patches. Simulation studies showed that the inference of our model depends on detection probability, local population size, and the implementation of robust sampling design. Our model provides reliable estimates of survival, reproduction, and emigration when detection probability is high, regardless of local population size or the type of sampling design. When detection probability is low, however, our model only provides reliable estimates of survival, reproduction, and emigration when local population size is moderate to high and robust sampling design is used. A sensitivity analysis showed that our model is robust against the violation of the assumption that movement only occurs among adjacent habitat patches, suggesting wide applications of this model. Our model can be used to improve our understanding of metapopulation dynamics based on count data that are relatively easy to collect in many systems.

  7. Explicit constructions of automorphic L-functions

    CERN Document Server

    Gelbart, Stephen; Rallis, Stephen

    1987-01-01

    The goal of this research monograph is to derive the analytic continuation and functional equation of the L-functions attached by R.P. Langlands to automorphic representations of reductive algebraic groups. The first part of the book (by Piatetski-Shapiro and Rallis) deals with L-functions for the simple classical groups; the second part (by Gelbart and Piatetski-Shapiro) deals with non-simple groups of the form G GL(n), with G a quasi-split reductive group of split rank n. The method of proof is to construct certain explicit zeta-integrals of Rankin-Selberg type which interpolate the relevant Langlands L-functions and can be analyzed via the theory of Eisenstein series and intertwining operators. This is the first time such an approach has been applied to such general classes of groups. The flavor of the local theory is decidedly representation theoretic, and the work should be of interest to researchers in group representation theory as well as number theory.

  8. Explicit logic circuits discriminate neural states.

    Directory of Open Access Journals (Sweden)

    Lane Yoder

    Full Text Available The magnitude and apparent complexity of the brain's connectivity have left explicit networks largely unexplored. As a result, the relationship between the organization of synaptic connections and how the brain processes information is poorly understood. A recently proposed retinal network that produces neural correlates of color vision is refined and extended here to a family of general logic circuits. For any combination of high and low activity in any set of neurons, one of the logic circuits can receive input from the neurons and activate a single output neuron whenever the input neurons have the given activity state. The strength of the output neuron's response is a measure of the difference between the smallest of the high inputs and the largest of the low inputs. The networks generate correlates of known psychophysical phenomena. These results follow directly from the most cost-effective architectures for specific logic circuits and the minimal cellular capabilities of excitation and inhibition. The networks function dynamically, making their operation consistent with the speed of most brain functions. The networks show that well-known psychophysical phenomena do not require extraordinarily complex brain structures, and that a single network architecture can produce apparently disparate phenomena in different sensory systems.

  9. Explicit information reduces discounting behavior in monkeys

    Directory of Open Access Journals (Sweden)

    John ePearson

    2010-12-01

    Full Text Available Animals are notoriously impulsive in common laboratory experiments, preferring smaller, sooner rewards to larger, delayed rewards even when this reduces average reward rates. By contrast, the same animals often engage in natural behaviors that require extreme patience, such as food caching, stalking prey, and traveling long distances to high quality food sites. One possible explanation for this discrepancy is that standard laboratory delay discounting tasks artificially inflate impulsivity by subverting animals’ common learning strategies. To test this idea, we examined choices made by rhesus macaques in two variants of a standard delay discounting task. In the conventional variant, post-reward delays were uncued and adjusted to render total trial length constant; in the second, all delays were cued explicitly. We found that measured discounting was significantly reduced in the cued task, with discount rates well below those reported in studies using the standard uncued design. When monkeys had complete information, their decisions were more consistent with a strategy of reward rate maximization. These results indicate that monkeys, and perhaps other animals, are more patient than is normally assumed, and that laboratory measures of delay discounting may overstate impulsivity.

  10. Estimation of Solvation Quantities from Experimental Thermodynamic Data: Development of the Comprehensive CompSol Databank for Pure and Mixed Solutes

    Science.gov (United States)

    Moine, Edouard; Privat, Romain; Sirjean, Baptiste; Jaubert, Jean-Noël

    2017-09-01

    The Gibbs energy of solvation measures the affinity of a solute for its solvent and is thus a key property for the selection of an appropriate solvent for a chemical synthesis or a separation process. More fundamentally, Gibbs energies of solvation are choice data for developing and benchmarking molecular models predicting solvation effects. The Comprehensive Solvation—CompSol—database was developed with the ambition to propose very large sets of new experimental solvation chemical-potential, solvation entropy, and solvation enthalpy data of pure and mixed components, covering extended temperature ranges. For mixed compounds, the solvation quantities were generated in infinite-dilution conditions by combining experimental values of pure-component and binary-mixture thermodynamic properties. Three types of binary-mixture properties were considered: partition coefficients, activity coefficients at infinite dilution, and Henry's-law constants. A rigorous methodology was implemented with the aim to select data at appropriate conditions of temperature, pressure, and concentration for the estimation of solvation data. Finally, our comprehensive CompSol database contains 21 671 data associated with 1969 pure species and 70 062 data associated with 14 102 binary mixtures (including 760 solvation data related to the ionic-liquid class of solvents). On the basis of the very large amount of experimental data contained in the CompSol database, it is finally discussed how solvation energies are influenced by hydrogen-bonding association effects.

  11. From Explicit to Symbolic Types for Communication Protocols in CCS

    DEFF Research Database (Denmark)

    Nielson, Hanne Riis; Nielson, Flemming; Kreiker, Jörg

    2012-01-01

    We study communication protocols having several rounds and expressed in value passing CCS. We develop a type-based analysis for providing an explicit record of all communications and show the usual subject reduction result. Since the explicit records can be infinitely large, we also develop a type......-based analysis for providing a finite, symbolic record of all communications. We show that it correctly approximates the explicit record and prove an adequacy result for it....

  12. Spatially explicit modeling in ecology: A review

    Science.gov (United States)

    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.

  13. Spatially explicit methane inventory for Switzerland

    Science.gov (United States)

    Hiller, Rebecca; Bretscher, Daniel; DelSontro, Tonya; Eugster, Werner; Henne, Stephan; Henneberger, Ruth; Künzle, Thomas; Merbold, Lutz; Neininger, Bruno; Schellenberger, Andreas; Schroth, Martin; Buchmann, Nina; Brunner1, Dominik

    2013-04-01

    Spatially explicit greenhouse gas inventories are gaining in importance as a tool for policy makers to plan and control mitigation measures, and are a required input for atmospheric models used to relate atmospheric concentration measurements with upstream sources. In order to represent the high spatial heterogeneity in Switzerland, we compiled the national methane inventory into a 500 m x 500 m cadaster. In addition to the anthropogenic emissions reported to the United Nation Framework Convention on Climate Change (UNFCCC), we also included natural and semi-natural methane fluxes, i.e., emissions from lakes and reservoirs, wetlands, wild animals as well as forest uptake. Methane emissions were disaggregated according to geostatistical information about source location and extent. In Switzerland, highest methane emissions originate from the agricultural sector (152 Gg CH4 yr-1), followed by emissions from waste management (16 Gg CH4 yr-1) with highest contributions from landfills, and the energy sector (13 Gg CH4 yr-1) with highest contributions from the distribution of natural gas. Natural and semi-natural emissions only add a small amount (inventory was evaluated against methane concentrations measured from a small research aircraft (METAIR-DIMO) above the Swiss Plateau on 18 different days from May 2009 to August 2010 over. Source sensitivities of the air measured were determined by backward runs of the Lagrangian particle dispersion model FLEXPART-COSMO. Source sensitivities were multiplied with the methane inventory to derive simulated methane concentration time series. While the pattern of the variations can be reproduced well for some flight days (correlation coefficient up to 0.75), the amplitude of the variations for the simulated time series is underestimated by at least 20% suggesting an underestimation of CH4 emissions by the inventory, which is also concluded from inverse estimation using a Bayesian approach.

  14. Calculation of the Gibbs Free Energy of Solvation and Dissociation of HCl in Water via Monte Carlo Simulations and Continuum Solvation Models

    Science.gov (United States)

    2013-01-01

    concentrations and temperatures,12–19 including vapor- and liquid-phase mole fractions of HCl as functions of tempera- ture.20 Equations to predict the...Å for O, q = !0.15 |e| for Cl and !0.784 |e| for O). The Lorentz– Berthelot combining rules74 were used for unlike interactions, and all interactions...from the corresponding fixed- concentration Gibbs free energies of solvation calculated by the following equation DG(S;XðTÞ ¼ DG ( S;X;refð298Þ þ DG

  15. Expanding the structural landscape of niclosamide: a high Z ' polymorph, two new solvates and monohydrate HA

    DEFF Research Database (Denmark)

    Sovago, Ioana; Bond, Andrew D.

    2015-01-01

    that this compound is related to the methanol solvate of niclosamide [Harriss, Wilson & Radosevljevic Evans (2014). Acta Cryst. C70, 758-763], but it is found that the two are not fully isostructural: they contain isostructural two-dimensional layers, but the layers are arranged differently in the two structures....... This suggests that HA may have the potential for polytypism, and features in the Rietveld difference curve indicate that a polytype fully isostructural with the methanol solvate might be present....

  16. Investigation of the Human Disease Osteogenesis Imperfecta: A Research-Based Introduction to Concepts and Skills in Biomolecular Analysis

    Science.gov (United States)

    Mate, Karen; Sim, Alistair; Weidenhofer, Judith; Milward, Liz; Scott, Judith

    2013-01-01

    A blended approach encompassing problem-based learning (PBL) and structured inquiry was used in this laboratory exercise based on the congenital disease Osteogenesis imperfecta (OI), to introduce commonly used techniques in biomolecular analysis within a clinical context. During a series of PBL sessions students were presented with several…

  17. Native fluorescence detection of biomolecular and pharmaceutical compounds in capillary electrophoresis: detector designs, performance and applications: A review

    NARCIS (Netherlands)

    de Kort, B.J.; de Jong, G.J.; Somsen, G.W.

    2013-01-01

    This review treats the coupling of capillary electrophoresis (CE) with fluorescence detection (Flu) for the analysis of natively fluorescent biomolecular and pharmaceutical compounds. CE-Flu combines the excellent separation efficiency of CE with the high selectivity and sensitivity of Flu. In

  18. Electrochemical sensor for multiplex screening of genetically modified DNA: identification of biotech crops by logic-based biomolecular analysis.

    Science.gov (United States)

    Liao, Wei-Ching; Chuang, Min-Chieh; Ho, Ja-An Annie

    2013-12-15

    Genetically modified (GM) technique, one of the modern biomolecular engineering technologies, has been deemed as profitable strategy to fight against global starvation. Yet rapid and reliable analytical method is deficient to evaluate the quality and potential risk of such resulting GM products. We herein present a biomolecular analytical system constructed with distinct biochemical activities to expedite the computational detection of genetically modified organisms (GMOs). The computational mechanism provides an alternative to the complex procedures commonly involved in the screening of GMOs. Given that the bioanalytical system is capable of processing promoter, coding and species genes, affirmative interpretations succeed to identify specified GM event in terms of both electrochemical and optical fashions. The biomolecular computational assay exhibits detection capability of genetically modified DNA below sub-nanomolar level and is found interference-free by abundant coexistence of non-GM DNA. This bioanalytical system, furthermore, sophisticates in array fashion operating multiplex screening against variable GM events. Such a biomolecular computational assay and biosensor holds great promise for rapid, cost-effective, and high-fidelity screening of GMO. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Optical oblique-incidence reflectivity difference microscopy: Application to label-free detection of reactions in biomolecular microarrays

    Science.gov (United States)

    Landry, James Paul

    2008-04-01

    Biomolecular microarrays have emerged as a leading technology for high-throughput in vitro assays in genomics and proteomics. Microarrays contain 100 to 100,000 distinct biomolecular features immobilized on a substrate at high density, enabling parallel assays of entire biomolecular systems or screens of large biomolecular libraries on a single glass slide. Microarrays are typically detected by reacting immobilized targets with fluorescently-labeled probes. For many biomolecules, particularly structurally and functionally diverse proteins, modification with labeling-agents can alter their function. For this reason, it is important to develop label-free microarray detection technology to complement standard fluorescence-based detection. In this dissertation, I report my research into the development of optical oblique-incidence reflectivity difference (OI-RD) microscopy for application to high-throughput and label-free detection of biomolecular microarrays in end-point and real-time modalities. OI-RD is a versatile and sensitive form of nulling polarization-modulated ellipsometry. By reflecting light at oblique incidence from a surface, OI-RD measures changes in thickness and dielectric response of ultrathin molecular layers through disproportionate responses of s- and p-polarization reflectivities. In this dissertation I given an account of the engineering and operation of the first OI-RD microscopes and mathematical theory underpinning them. I then report experiments showing label-free OI-RD detection of DNA hybridization and antibody-antigen binding reactions in microarrays fabricated on standard chemically functionalized glass slides. The experiments demonstrate that: (1) The OI-RD signal quantifies biomolecular film properties, in particular, surface mass density, coverage, and orientation of biomolecules in the films. (2) The properties of targets, probes, and other biomolecular entities within the microarray can be measured throughout the microarray usage

  20. Crystallization of toxic glycol solvates of rifampin from glycerin and propylene glycol contaminated with ethylene glycol or diethylene glycol.

    Science.gov (United States)

    de Villiers, Melgardt M; Caira, Mino R; Li, Jinjing; Strydom, Schalk J; Bourne, Susan A; Liebenberg, Wilna

    2011-06-06

    This study was initiated when it was suspected that syringe blockage experienced upon administration of a compounded rifampin suspension was caused by the recrystallization of toxic glycol solvates of the drug. Single crystal X-ray structure analysis, powder X-ray diffraction, thermal analysis and gas chromatography were used to identify the ethylene glycol in the solvate crystals recovered from the suspension. Controlled crystallization and solubility studies were used to determine the ease with which toxic glycol solvates crystallized from glycerin and propylene glycol contaminated with either ethylene or diethylene glycol. The single crystal structures of two distinct ethylene glycol solvates of rifampin were solved while thermal analysis, GC analysis and solubility studies confirmed that diethylene glycol solvates of the drug also crystallized. Controlled crystallization studies showed that crystallization of the rifampin solvates from glycerin and propylene glycol depended on the level of contamination and changes in the solubility of the drug in the contaminated solvents. Although the exact source of the ethylene glycol found in the compounded rifampin suspension is not known, the results of this study show how important it is to ensure that the drug and excipients comply with pharmacopeial or FDA standards.

  1. Anisotropic solvent model of the lipid bilayer. 1. Parameterization of long-range electrostatics and first solvation shell effects

    Science.gov (United States)

    Lomize, Andrei L.; Pogozheva, Irina; Mosberg, Henry I

    2011-01-01

    A new implicit solvation model was developed for calculating free energies of transfer of molecules from water to any solvent with defined bulk properties. The transfer energy was calculated as a sum of the first solvation shell energy and the long-range electrostatic contribution. The first term was proportional to solvent accessible surface area and solvation parameters (σi) for different atom types. The electrostatic term was computed as a product of group dipole moments and dipolar solvation parameter (η) for neutral molecules, or using a modified Born equation for ions. The regression coefficients in linear dependencies of solvation parameters σi and η on dielectric constant, solvatochromic polarizability parameter π*, and hydrogen-bonding donor and acceptor capacities of solvents were optimized using 1269 experimental transfer energies from 19 organic solvents to water. The root-mean-square errors for neutral compounds and ions were 0.82 and 1.61 kcal/mol, respectively. Quantification of energy components demonstrates the dominant roles of hydrophobic effect for non-polar atoms and of hydrogen-bonding for polar atoms. The estimated first solvation shell energy outweighs the long-range electrostatics for most compounds including ions. The simplicity and computational efficiency of the model allows its application for modeling of macromolecules in anisotropic environments, such as biological membranes. PMID:21438609

  2. Comparison of the crystal structures and thermochemistry of a novel soluble guanylate cyclase stimulator riociguat and its solvates.

    Science.gov (United States)

    Zhou, Xinbo; Hu, Xiurong; Gu, Jianming; Zhu, Jianrong

    2017-10-01

    Riociguat (Rio) is the first oral soluble guanylate cyclase stimulator to be approved for pulmonary arterial hypertension. In this study, form (II) of riociguat and three solvates with acetonitrile [form (III)], N,N-dimethylformamide [form (IV)] and ethyl acetate [form (V)] were crystallized. They were identified and characterized by differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction, and their crystal structures were determined by single-crystal X-ray diffraction. No crystal structure has previously been reported for the known form (II) of riociguat. Crystal structure determination of Rio and its new solvates revealed that the dimeric R(2)2(14) motif is common in both structures. The crystal packing of solvates adopts channel-like patterns, whereas form (II) of riociguat adopts sheet-like patterns. Strong π-π interactions exist in the above four forms. The conformation of the riociguat in one molecule of 0.5-DMF solvate was found to be significantly different from the conformations found in the other solvates. Desolvation of the three solvates was studied by thermogravimetric analysis and X-ray diffraction, and was shown to transform them into form (I) of riociguat.

  3. Using Nature's "Tricks" To Rationally Tune the Binding Properties of Biomolecular Receptors.

    Science.gov (United States)

    Ricci, Francesco; Vallée-Bélisle, Alexis; Simon, Anna J; Porchetta, Alessandro; Plaxco, Kevin W

    2016-09-20

    The biosensor community has long focused on achieving the lowest possible detection limits, with specificity (the ability to differentiate between closely similar target molecules) and sensitivity (the ability to differentiate between closely similar target concentrations) largely being relegated to secondary considerations and solved by the inclusion of cumbersome washing and dilution steps or via careful control experimental conditions. Nature, in contrast, cannot afford the luxury of washing and dilution steps, nor can she arbitrarily change the conditions (temperature, pH, ionic strength) under which binding occurs in the homeostatically maintained environment within the cell. This forces evolution to focus at least as much effort on achieving optimal sensitivity and specificity as on achieving low detection limits, leading to the "invention" of a number of mechanisms, such as allostery and cooperativity, by which the useful dynamic range of receptors can be tuned, extended, narrowed, or otherwise optimized by design, rather than by sample manipulation. As the use of biomolecular receptors in artificial technologies matures (i.e., moves away from multistep, laboratory-bound processes and toward, for example, systems supporting continuous in vivo measurement) and these technologies begin to mimic the reagentless single-step convenience of naturally occurring chemoperception systems, the ability to artificially design receptors of enhanced sensitivity and specificity will likely also grow in importance. Thus motivated, we have begun to explore the adaptation of nature's solutions to these problems to the biomolecular receptors often employed in artificial biotechnologies. Using the population-shift mechanism, for example, we have generated nested sets of receptors and allosteric inhibitors that greatly expanded the normally limited (less than 100-fold) useful dynamic range of unmodified molecular and aptamer beacons, enabling the single-step (e.g., dilution

  4. Electrostatic Solvation Energy for Two Oppositely Charged Ions in a Solvated Protein System: Salt Bridges Can Stabilize Proteins

    Science.gov (United States)

    Gong, Haipeng; Freed, Karl F.

    2010-01-01

    Abstract Born-type electrostatic continuum methods have been an indispensable ingredient in a variety of implicit-solvent methods that reduce computational effort by orders of magnitude compared to explicit-solvent MD simulations and thus enable treatment using larger systems and/or longer times. An analysis of the limitations and failures of the Born approaches serves as a guide for fundamental improvements without diminishing the importance of prior works. One of the major limitations of the Born theory is the lack of a liquidlike description of the response of solvent dipoles to the electrostatic field of the solute and the changes therein, a feature contained in the continuum Langevin-Debye (LD) model applied here to investigate how Coulombic interactions depend on the location of charges relative to the protein/water boundary. This physically more realistic LD model is applied to study the stability of salt bridges. When compared head to head using the same (independently measurable) physical parameters (radii, dielectric constants, etc.), the LD model is in good agreement with observations, whereas the Born model is grossly in error. Our calculations also suggest that a salt bridge on the protein's surface can be stabilizing when the charge separation is ≤4 Å. PMID:20141761

  5. Orientational order in the stable buckminster fullerene solvate C60·2CBr2H2

    Science.gov (United States)

    Ye, J.; Barrio, M.; Negrier, Ph.; Qureshi, N.; Rietveld, I. B.; Céolin, R.; Tamarit, J. Ll.

    2017-04-01

    Crystals of the solvate C60·2CBr2H2 (monoclinic C2/ m), which is stable in air, were grown by slow evaporation of solutions of C60 in CBr2H2 at room temperature. The high enthalpy change for the complete desolvation process, 54.9 kJ mol-1 of solvent, as well as the relatively large negative excess volume of -49.6 Å3 indicate the presence of strong intermolecular interactions between C60 and CBr2H2. The strong intermolecular interactions are consistent with an overall orientational order for the C60 and the CBr2H2 molecules in the solvate as found by the Rietveld refinement of its crystal structure.

  6. A Valence-Bond Nonequilibrium Solvation Model for a Twisting Cyanine Dye

    CERN Document Server

    McConnell, Sean; Olsen, Seth

    2014-01-01

    We study a two-state valence-bond electronic Hamiltonian model of non-equilibrium solvation during the excited-state twisting reaction of monomethine cyanines. These dyes are of interest because of the strong environment-dependent enhancement of their fluorescence quantum yield that results from suppression of competing non-radiative decay via twisted internal charge-transfer (TICT) states. For monomethine cyanines, where the ground state is a superposition of structures with different bond and charge localization, there are two twisting pathways with different charge localization in the excited state. The Hamiltonian designed to be as simple as possible consistent with a few well-enumerated assumptions. It is defined by three parameters and is a function of two $\\pi$-bond twisting angle coordinates and a single solvation coordinate. For parameters corresponding to symmetric monomethines, there are two low-energy twisting channels on the excited-state surface that lead to a manifold of twisted intramolecular ...

  7. Sparingly Solvating Electrolytes for High Energy Density Lithium-Sulfur Batteries

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Lei; Curtiss, Larry A.; Zavadil, Kevin R.; Gewirth, Andrew A.; Shao, Yuyan; Gallagher, Kevin

    2016-07-11

    Moving to lighter and less expensive battery chemistries compared to lithium-ion requires the control of energy storage mechanisms based on chemical transformations rather than intercalation. Lithium sulfur (Li/S) has tremendous theoretical specific energy, but contemporary approaches to control this solution-mediated, precipitation-dissolution chemistry requires using large excesses of electrolyte to fully solubilize the polysulfide intermediate. Achieving reversible electrochemistry under lean electrolyte operation is the only path for Li/S to move beyond niche applications to potentially transformational performance. An emerging topic for Li/S research is the use of sparingly solvating electrolytes and the creation of design rules for discovering new electrolyte systems that fundamentally decouple electrolyte volume from reaction mechanism. This perspective presents an outlook for sparingly solvating electrolytes as the key path forward for longer-lived, high-energy density Li/S batteries including an overview of this promising new concept and some strategies for accomplishing it.

  8. Influence of Solvation and Structural Contributions on Fluorescence of Dipyrrine Dyes.

    Science.gov (United States)

    Ksenofontov, A A; Guseva, G B; Antina, E V; Vyugin, A I; Nuraneeva, E N

    2015-11-01

    The results of quantum-chemical and spectral researches of zinc((II)) complexes with alkylated dipyrrine and 3,3'-, 2,3'- and 2,2'-bis(dipyrrine)s in non-polar and polar solvents and their binary mixtures are presented. It was investigated the efficiency of the fluorescence quenching of fluorophores depending on of the solvation and structural contributions. Found that 3,3'-bis(dipyrrinato)zinc((II)) demonstrates the highest sensitivity of the fluorescence to the presence of the electron-donor component compared with the studied complexes. The obtained results allow to offer dipyrrine and bis(dipyrrine) zinc((II)) complexes as new, highly sensitive and selective fluorescent sensors of the N- and O-containing toxicants. Graphical Abstract Influence of solvation and structural contributions on fluorescence of dipyrrine dyes.

  9. SOLVATION STRUCTURE DETERMINATION OF Ni2+ ION IN WATER BY MEANS OF MONTE CARLO METHOD

    Directory of Open Access Journals (Sweden)

    Tutik Arindah

    2010-06-01

    Full Text Available Determination of solvation structure of Ni2+ ion in water has been achieved using Monte Carlo method using canonic assemble (NVT constant. Simulation of a Ni2+ ion in 215 H2O molecules has been done under NVT condition (298.15 K. The results showed that number of H2O molecules surround Ni2+ ion were 8 molecules in first shell and 17 molecules in second shell, interaction energy of Ni2+-H2O in first shell was -68.7 kcal/mol and in second shell was -9.8 kcal/mol, and there were two angles of O-Ni2+-O, i.e. 74o and 142o. According to those results, the solvation structure of Ni2+ ion in water was cubic antisymetric.   Keywords: Water simulation, Monte Carlo simulation

  10. New estimators for calculating solvation entropy and enthalpy and comparative assessments of their accuracy and precision.

    Science.gov (United States)

    Wyczalkowski, Matthew A; Vitalis, Andreas; Pappu, Rohit V

    2010-06-24

    We present two new methods for estimating the entropy and enthalpy decomposition of free energy calculations. These methods are based on temperature derivatives of the Bennett Acceptance Ratio and the Multistate Bennett Acceptance Ratio estimators, respectively. We test the accuracy of these new estimators using a simple one-dimensional model. A detailed assessment of their performance is reported by studying the solvation of N-methylacetamide. Finally, we quantify the free energies of solvation for 11 model compounds using the OPLS-AA force field and a variation of this force field. Thermodynamic decompositions of these calculated free energies are obtained to highlight the utility of these quantities for refining force field parameters by comparing computed free energies and their decompositions to their experimental counterparts.

  11. Hybrid Perovskite Thin-Film Photovoltaics: In Situ Diagnostics and Importance of the Precursor Solvate Phases

    KAUST Repository

    Munir, Rahim

    2016-11-07

    Solution-processed hybrid perovskite semiconductors attract a great deal of attention, but little is known about their formation process. The one-step spin-coating process of perovskites is investigated in situ, revealing that thin-film formation is mediated by solid-state precursor solvates and their nature. The stability of these intermediate phases directly impacts the quality and reproducibility of thermally converted perovskite films and their photovoltaic performance.

  12. Solvated fullerenes, a new class of carbon materials suitable for high-pressure studies: A review

    Science.gov (United States)

    Wang, Lin

    2015-09-01

    As the list of known carbon compounds grows longer, solvated fullerenes have become a more important class of carbon materials. Their general properties and methods of synthesis have both attracted considerable attention. The study of the behavior of these compounds under high-pressure conditions has revealed several new phenomena that have never been observed in pure fullerene. This article is a review of all recent progress in this field.

  13. Directing the Lithium–Sulfur Reaction Pathway via Sparingly Solvating Electrolytes for High Energy Density Batteries

    Science.gov (United States)

    2017-01-01

    The lithium–sulfur battery has long been seen as a potential next generation battery chemistry for electric vehicles owing to the high theoretical specific energy and low cost of sulfur. However, even state-of-the-art lithium–sulfur batteries suffer from short lifetimes due to the migration of highly soluble polysulfide intermediates and exhibit less than desired energy density due to the required excess electrolyte. The use of sparingly solvating electrolytes in lithium–sulfur batteries is a promising approach to decouple electrolyte quantity from reaction mechanism, thus creating a pathway toward high energy density that deviates from the current catholyte approach. Herein, we demonstrate that sparingly solvating electrolytes based on compact, polar molecules with a 2:1 ratio of a functional group to lithium salt can fundamentally redirect the lithium–sulfur reaction pathway by inhibiting the traditional mechanism that is based on fully solvated intermediates. In contrast to the standard catholyte sulfur electrochemistry, sparingly solvating electrolytes promote intermediate- and short-chain polysulfide formation during the first third of discharge, before disproportionation results in crystalline lithium sulfide and a restricted fraction of soluble polysulfides which are further reduced during the remaining discharge. Moreover, operation at intermediate temperatures ca. 50 °C allows for minimal overpotentials and high utilization of sulfur at practical rates. This discovery opens the door to a new wave of scientific inquiry based on modifying the electrolyte local structure to tune and control the reaction pathway of many precipitation–dissolution chemistries, lithium–sulfur and beyond. PMID:28691072

  14. Using the theoretical linear energy solvation energy relationship to correlate and predict nasal pungency thresholds.

    Science.gov (United States)

    Famini, George R; Aguiar, Denise; Payne, Marvin A; Rodriquez, Ryan; Wilson, Leland Y

    2002-01-01

    The theoretical linear solvation energy relationship (TLSER) has been used to correlate and characterize 44 nasal pungency threshold (NPT) values in man with parameters derived from semi-empirical molecular orbital theory. The resulting relationship provides good correlative (R2 > 0.92) and predictive (R2cy > 0.88) capability. In addition, the TLSER parameters are used as a molecular probe to attempt to understand the fundamental properties influencing nasal pungency.

  15. ABSINTH: a new continuum solvation model for simulations of polypeptides in aqueous solutions.

    Science.gov (United States)

    Vitalis, Andreas; Pappu, Rohit V

    2009-04-15

    A new implicit solvation model for use in Monte Carlo simulations of polypeptides is introduced. The model is termed ABSINTH for self-Assembly of Biomolecules Studied by an Implicit, Novel, and Tunable Hamiltonian. It is designed primarily for simulating conformational equilibria and oligomerization reactions of intrinsically disordered proteins in aqueous solutions. The paradigm for ABSINTH is conceptually similar to the EEF1 model of Lazaridis and Karplus (Proteins 1999, 35, 133). In ABSINTH, the transfer of a polypeptide solute from the gas phase into a continuum solvent is the sum of a direct mean field interaction (DMFI), and a term to model the screening of polar interactions. Polypeptide solutes are decomposed into a set of distinct solvation groups. The DMFI is a sum of contributions from each of the solvation groups, which are analogs of model compounds. Continuum-mediated screening of electrostatic interactions is achieved using a framework similar to the one used for the DMFI. Promising results are shown for a set of test cases. These include the calculation of NMR coupling constants for short peptides, the assessment of the thermal stability of two small proteins, reversible folding of both an alpha-helix and a beta-hairpin forming peptide, and the polymeric properties of intrinsically disordered polyglutamine peptides of varying lengths. The tests reveal that the computational expense for simulations with the ABSINTH implicit solvation model increase by a factor that is in the range of 2.5-5.0 with respect to gas-phase calculations. 2008 Wiley Periodicals, Inc.

  16. Directing the Lithium-Sulfur Reaction Pathway via Sparingly Solvating Electrolytes for High Energy Density Batteries.

    Science.gov (United States)

    Lee, Chang-Wook; Pang, Quan; Ha, Seungbum; Cheng, Lei; Han, Sang-Don; Zavadil, Kevin R; Gallagher, Kevin G; Nazar, Linda F; Balasubramanian, Mahalingam

    2017-06-28

    The lithium-sulfur battery has long been seen as a potential next generation battery chemistry for electric vehicles owing to the high theoretical specific energy and low cost of sulfur. However, even state-of-the-art lithium-sulfur batteries suffer from short lifetimes due to the migration of highly soluble polysulfide intermediates and exhibit less than desired energy density due to the required excess electrolyte. The use of sparingly solvating electrolytes in lithium-sulfur batteries is a promising approach to decouple electrolyte quantity from reaction mechanism, thus creating a pathway toward high energy density that deviates from the current catholyte approach. Herein, we demonstrate that sparingly solvating electrolytes based on compact, polar molecules with a 2:1 ratio of a functional group to lithium salt can fundamentally redirect the lithium-sulfur reaction pathway by inhibiting the traditional mechanism that is based on fully solvated intermediates. In contrast to the standard catholyte sulfur electrochemistry, sparingly solvating electrolytes promote intermediate- and short-chain polysulfide formation during the first third of discharge, before disproportionation results in crystalline lithium sulfide and a restricted fraction of soluble polysulfides which are further reduced during the remaining discharge. Moreover, operation at intermediate temperatures ca. 50 °C allows for minimal overpotentials and high utilization of sulfur at practical rates. This discovery opens the door to a new wave of scientific inquiry based on modifying the electrolyte local structure to tune and control the reaction pathway of many precipitation-dissolution chemistries, lithium-sulfur and beyond.

  17. Atomistic characterization of the active-site solvation dynamics of a model photocatalyst

    DEFF Research Database (Denmark)

    Brandt van Driel, Tim; Kjær, Kasper Skov; Hartsock, Robert W.

    2016-01-01

    The interactions between the reactive excited state of molecular photocatalysts and surrounding solvent dictate reaction mechanisms and pathways, but are not readily accessible to conventional optical spectroscopic techniques. Here we report an investigation of the structural and solvation dynami...... of the iridium atoms by the acetonitrile solvent and demonstrate the viability of using diffuse X-ray scattering at free-electron laser sources for studying the dynamics of photocatalysis....

  18. Calculation of solvation free energy from quantum mechanical charge density and continuum dielectric theory.

    Science.gov (United States)

    Wang, Mingliang; Wong, Chung F

    2006-04-13

    We have combined ultrasoft pseudopotential density functional theory utilizing plane wave basis with a Poisson-Boltzmann/solvent-accessible surface area (PB/SA) model to calculate the solvation free energy of small neutral organic compounds in water. The solute charge density obtained from density functional theory was directly used in solving the Poisson-Boltzmann equation to obtain the reaction field. The polarized electronic wave function of the solute in the solvent was solved by including the reaction field in the density functional Hamiltonian. The quantum mechanical and Poisson-Boltzmann equations were solved self-consistently until the charge density and reaction field converged. Using the solute charge density directly instead of a point-charge representation permitted asymmetric distortion and spreading out of the electron cloud. Because the electron density could leave the van der Waals surface to penetrate into the high-dielectric solvent, the reaction field generated by this density was generally smaller than that obtained by using the point-charge representation. In applying this model to calculate the solvation free energy of 31 small neutral organic molecules spanning a range of 25 kcal/mol, we obtained a root-mean-square error of only 1.3 kcal/mol if we allowed one adjustable parameter to shift the calculated solvation free energy.

  19. Elucidating the Solvation Structure and Dynamics of Lithium Polysulfides Resulting from Competitive Salt and Solvent Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Rajput, Nav Nidhi; Murugesan, Vijayakumar; Shin, Yongwoo; Han, Kee Sung; Lau, Kah Chun; Chen, Junzheng; Liu, Jun; Curtiss, Larry A.; Mueller, Karl T.; Persson, Kristin A.

    2017-04-10

    Fundamental molecular level understanding of functional properties of liquid solutions provides an important basis for designing optimized electrolytes for numerous applica-tions. In particular, exhaustive knowledge of solvation structure, stability and transport properties is critical for developing stable electrolytes for fast charging and high energy density next-generation energy storage systems. Here we report the correlation between solubility, solvation structure and translational dynamics of a lithium salt (Li-TFSI) and polysulfides species using well-benchmarked classical molecular dynamics simulations combined with nuclear magnetic resonance (NMR). It is observed that the polysulfide chain length has a significant effect on the ion-ion and ion-solvent interaction as well as on the diffusion coefficient of the ionic species in solution. In particular, extensive cluster formation is observed in lower order poly-sulfides (Sx2-; x≤4), whereas the longer polysulfides (Sx2-; x>4) show high solubility and slow dynamics in the solu-tion. It is observed that optimal solvent/salt ratio is essen-tial to control the solubility and conductivity as the addi-tion of Li salt increases the solubility but decreases the mo-bility of the ionic species. This work provides a coupled theoretical and experimental study of bulk solvation struc-ture and transport properties of multi-component electro-lyte systems, yielding design metrics for developing optimal electrolytes with improved stability and solubility.

  20. Significance of solvated electrons (e(aq)-) as promoters of life on earth.

    Science.gov (United States)

    Getoff, Nikola

    2014-01-01

    Based on the present state of knowledge a new hypothesis concerning the origin of life on Earth is presented, and emphasizes the particular significance of solvated electrons (e(aq)(-)). Solvated electrons are produced in seawater, mainly by (40)K radiation and in atmospheric moisture by VUV light, electrical discharges and cosmic ray. Solvated electrons are involved in primary chemical processes and in biological processes. The conversion of aqueous CO2 and CO into simple organic substances, the generation of ammonia from N2 and water, the formation of amines, amino acids and simple proteins under the action of e(aq)(-) has been experimentally proven. Furthermore, it is supposed that the generation of the primitive cell and equilibria of primitive enzymes are also realized due to the strong reducing property of e(aq)(-). The presented hypothesis is mainly founded on recently obtained experimental results. The involvement of e(aq)(-) in such mechanisms, as well as their action as an initiator of life is also briefly discussed.

  1. High-dimensional neural network potentials for solvation: The case of protonated water clusters in helium

    Science.gov (United States)

    Schran, Christoph; Uhl, Felix; Behler, Jörg; Marx, Dominik

    2018-03-01

    The design of accurate helium-solute interaction potentials for the simulation of chemically complex molecules solvated in superfluid helium has long been a cumbersome task due to the rather weak but strongly anisotropic nature of the interactions. We show that this challenge can be met by using a combination of an effective pair potential for the He-He interactions and a flexible high-dimensional neural network potential (NNP) for describing the complex interaction between helium and the solute in a pairwise additive manner. This approach yields an excellent agreement with a mean absolute deviation as small as 0.04 kJ mol-1 for the interaction energy between helium and both hydronium and Zundel cations compared with coupled cluster reference calculations with an energetically converged basis set. The construction and improvement of the potential can be performed in a highly automated way, which opens the door for applications to a variety of reactive molecules to study the effect of solvation on the solute as well as the solute-induced structuring of the solvent. Furthermore, we show that this NNP approach yields very convincing agreement with the coupled cluster reference for properties like many-body spatial and radial distribution functions. This holds for the microsolvation of the protonated water monomer and dimer by a few helium atoms up to their solvation in bulk helium as obtained from path integral simulations at about 1 K.

  2. Synthesis, crystal structure and spectroscopic properties of ethanol solvated α-Keggin heteropolymolybdate

    Science.gov (United States)

    Tümer, Ferhan; Köse, Muhammet; Tümer, Mehmet

    2017-11-01

    In this study, the ethanol solvated α-Keggin heteropolymolybdate (A) was prepared and characterized by the spectroscopic methods such as single-crystal X-ray diffraction, Uv-vis, FT-IR and photoluminescence methods. Thermal analysis of the compound (A) was performed in the 20-1000 °C range in the N2 atmosphere and electrochemical studies were carried out in the 100-1000 mV/s scan rate range. The ethanol solvated α-Keggin compound exhibits three irreversible anodic and cathodic peak potentials. The structure of the Keggin type polyoxometalate compound was solved in trigonal unit cell and R-3 space group with Rfinal value of 0.0507. The structure of the compound contains H4[SiMo12O40] molecule and three ethanol solvates. The Hirshfeld surface for H4[SiMo12O40]·3EtOH was obtained to determine the interaction sites within the crystal structure. A cyclic hydrogen bond pattern was shown by a large number of fused spots in the fingerprint plot and these hydrogen bond contacts link the other symmetry-related molecules forming a 3D hydrogen bond networks. Hydrogen bond interactions resulted in the formation of honey comb structure.

  3. Band offsets across solid-liquid interfaces from continuum solvation methods

    Science.gov (United States)

    Sundararaman, Ravishankar; Ping, Yuan; Galli, Giulia A.; Goddard, William A., III

    2015-03-01

    The band edge positions of photo-electrodes relative to water redox potentials play an important role in determining the efficiency of the photo-electrochemical cell. Direct theoretical calculations of solid-liquid interfaces are expensive and simplified models are desirable for rapid theoretical screening of new materials. However, traditional solvation models are extensively fit to describe organic solutes and hence extrapolate poorly to highly-polar inorganic surfaces. We develop minimally-empirical continuum solvation models suitable for treating such surfaces and present theoretical predictions of the band positions of rutile TiO2 (110) and WO3 (001) surfaces in water. We obtain non-negligible solvation effects ~ 1-2 eV, in good agreement with experimental results. This material is based upon work performed by the Joint Center for Artificial Photosynthesis, a DOE Energy Innovation Hub, supported through the Office of Science of the U.S. Department of Energy under Award Number DE-SC0004993.

  4. Ermod: fast and versatile computation software for solvation free energy with approximate theory of solutions.

    Science.gov (United States)

    Sakuraba, Shun; Matubayasi, Nobuyuki

    2014-08-05

    ERmod is a software package to efficiently and approximately compute the solvation free energy using the method of energy representation. Molecular simulation is to be conducted at two condensed-phase systems of the solution of interest and the reference solvent with test-particle insertion of the solute. The subprogram ermod in ERmod then provides a set of energy distribution functions from the simulation trajectories, and another subprogram slvfe determines the solvation free energy from the distribution functions through an approximate functional. This article describes the design and implementation of ERmod, and illustrates its performance in solvent water for two organic solutes and two protein solutes. Actually, the free-energy computation with ERmod is not restricted to the solvation in homogeneous medium such as fluid and polymer and can treat the binding into weakly ordered system with nano-inhomogeneity such as micelle and lipid membrane. ERmod is available on web at http://sourceforge.net/projects/ermod. Copyright © 2014 Wiley Periodicals, Inc.

  5. Ultrafast fluxional exchange dynamics in electrolyte solvation sheath of lithium ion battery.

    Science.gov (United States)

    Lee, Kyung-Koo; Park, Kwanghee; Lee, Hochan; Noh, Yohan; Kossowska, Dorota; Kwak, Kyungwon; Cho, Minhaeng

    2017-03-08

    Lithium cation is the charge carrier in lithium-ion battery. Electrolyte solution in lithium-ion battery is usually based on mixed solvents consisting of polar carbonates with different aliphatic chains. Despite various experimental evidences indicating that lithium ion forms a rigid and stable solvation sheath through electrostatic interactions with polar carbonates, both the lithium solvation structure and more importantly fluctuation dynamics and functional role of carbonate solvent molecules have not been fully elucidated yet with femtosecond vibrational spectroscopic methods. Here we investigate the ultrafast carbonate solvent exchange dynamics around lithium ions in electrolyte solutions with coherent two-dimensional infrared spectroscopy and find that the time constants of the formation and dissociation of lithium-ion···carbonate complex in solvation sheaths are on a picosecond timescale. We anticipate that such ultrafast microscopic fluxional processes in lithium-solvent complexes could provide an important clue to understanding macroscopic mobility of lithium cation in lithium-ion battery on a molecular level.

  6. Influence of Spin-Orbit Quenching on the Solvation of Indium in Helium Droplets

    Science.gov (United States)

    Meyer, Ralf; Pototschnig, Johann V.; Ernst, Wolfgang E.; Hauser, Andreas W.

    2017-06-01

    Recent experimental interest of the collaborating group of M. Koch on the dynamics of electronic excitations of indium in helium droplets triggered a series of computational studies on the group 13 elements Al, Ga and In and their indecisive behavior between wetting and non wetting when placed onto superfluid helium droplets. We employ a combination of multiconfigurational self consistent field calculations (MCSCF) and multireference configuration interaction (MRCI) to calculate the diatomic potentials. Particularly interesting is the case of indium with an Ancilotto parameter λ close to the threshold value of 1.9. As shown by Reho et al. the spin-orbit splitting of metal atoms solvated in helium droplets is subject to a quenching effect. This can drastically change the solvation behavior. In this work we extend the approach presented by Reho et al. to include distance dependent spin-orbit coupling. The resulting potential surfaces are used to calculate the solvation energy of the ground state and the first excited state with orbital-free helium density functional theory. F. Ancilotto, P. B. Lerner and M. W. Cole, Journal of Low Temperature Physics, 1995, 101, 1123-1146 J. H. Reho, U. Merker, M. R. Radcliff, K. K. Lehmann and G. Scoles, The Journal of Physical Chemistry A, 2000, 104, 3620-3626

  7. CDPOP: A spatially explicit cost distance population genetics program

    Science.gov (United States)

    Erin L. Landguth; S. A. Cushman

    2010-01-01

    Spatially explicit simulation of gene flow in complex landscapes is essential to explain observed population responses and provide a foundation for landscape genetics. To address this need, we wrote a spatially explicit, individual-based population genetics model (CDPOP). The model implements individual-based population modelling with Mendelian inheritance and k-allele...

  8. A comparative study of explicit and implicit modelling of ...

    Indian Academy of Sciences (India)

    Abstract. In this paper, the explicit and implicit modelling of the subsegmental excitation information are experimentally compared. For explicit modelling, the static and dynamic values of the standard Liljencrants–Fant (LF) parameters that model the glottal flow derivative (GFD) are used. A simplified approximation method is.

  9. Explicit and Implicit Grammar Instructions in Higher Learning Institutions

    Science.gov (United States)

    Rahman, Ayuni Madarina Abdul; Rashid, Radzuwan Ab

    2017-01-01

    Two universally accepted approaches to grammar instruction are explicit and implicit teaching of the grammar. Both approaches have their own strengths and limitations. Educators may face a dilemma whether to teach grammar explicitly or implicitly. This paper aims to provide insights into the educators' beliefs towards grammar teaching in Malaysian…

  10. "Make It Explicit!": Improving Collaboration through Increase of Script Coercion

    Science.gov (United States)

    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…

  11. Age and time effects on implicit and explicit learning

    NARCIS (Netherlands)

    Verneau, M.; Kamp, J. van der; Savelsbergh, G.J.P.; Looze, M.P. de

    2014-01-01

    Study Context: It has been proposed that effects of aging are more pronounced for explicit than for implicit motor learning. The authors evaluated this claim by comparing the efficacy of explicit and implicit learning of a movement sequence in young and older adults, and by testing the resilience

  12. Age and Time Effects on Implicit and Explicit Learning

    NARCIS (Netherlands)

    Verneau, M.M.N.; van der Kamp, J.; Savelsbergh, G.J.P.; de Looze, M.P.

    2014-01-01

    Study Context: It has been proposed that effects of aging are more pronounced for explicit than for implicit motor learning. The authors evaluated this claim by comparing the efficacy of explicit and implicit learning of a movement sequence in young and older adults, and by testing the resilience

  13. Realization of Associative Memory in an Enzymatic Process: Toward Biomolecular Networks with Learning and Unlearning Functionalities.

    Science.gov (United States)

    Bocharova, Vera; MacVittie, Kevin; Chinnapareddy, Soujanya; Halámek, Jan; Privman, Vladimir; Katz, Evgeny

    2012-05-17

    We report a realization of an associative memory signal/information processing system based on simple enzyme-catalyzed biochemical reactions. Optically detected chemical output is always obtained in response to the triggering input, but the system can also "learn" by association, to later respond to the second input if it is initially applied in combination with the triggering input as the "training" step. This second chemical input is not self-reinforcing in the present system, which therefore can later "unlearn" to react to the second input if it is applied several times on its own. Such processing steps realized with (bio)chemical kinetics promise applications of bioinspired/memory-involving components in "networked" (concatenated) biomolecular processes for multisignal sensing and complex information processing.

  14. Amplified vibrational circular dichroism as a probe of local biomolecular structure.

    Science.gov (United States)

    Domingos, Sérgio R; Huerta-Viga, Adriana; Baij, Lambert; Amirjalayer, Saeed; Dunnebier, Dorien A E; Walters, Annemarie J C; Finger, Markus; Nafie, Laurence A; de Bruin, Bas; Buma, Wybren Jan; Woutersen, Sander

    2014-03-05

    We show that the VCD signal intensities of amino acids and oligopeptides can be enhanced by up to 2 orders of magnitude by coupling them to a paramagnetic metal ion. If the redox state of the metal ion is changed from paramagnetic to diamagnetic the VCD amplification vanishes completely. From this observation and from complementary quantum-chemical calculations we conclude that the observed VCD amplification finds its origin in vibronic coupling with low-lying electronic states. We find that the enhancement factor is strongly mode dependent and that it is determined by the distance between the oscillator and the paramagnetic metal ion. This localized character of the VCD amplification provides a unique tool to specifically probe the local structure surrounding a paramagnetic ion and to zoom in on such local structure within larger biomolecular systems.

  15. AFMPB: An Adaptive Fast Multipole Poisson-Boltzmann Solver for Calculating Electrostatics in Biomolecular Systems

    Science.gov (United States)

    Lu, Benzhuo; Cheng, Xiaolin; Huang, Jingfang; McCammon, J. Andrew

    2010-01-01

    A Fortran program package is introduced for rapid evaluation of the electrostatic potentials and forces in biomolecular systems modeled by the linearized Poisson-Boltzmann equation. The numerical solver utilizes a well-conditioned boundary integral equation (BIE) formulation, a node-patch discretization scheme, a Krylov subspace iterative solver package with reverse communication protocols, and an adaptive new version of fast multipole method in which the exponential expansions are used to diagonalize the multipole to local translations. The program and its full description, as well as several closely related libraries and utility tools are available at http://lsec.cc.ac.cn/lubz/afmpb.html and a mirror site at http://mccammon.ucsd.edu/. This paper is a brief summary of the program: the algorithms, the implementation and the usage. PMID:20532187

  16. Biomolecular Structure Information from High-Speed Quantum Mechanical Electronic Spectra Calculation.

    Science.gov (United States)

    Seibert, Jakob; Bannwarth, Christoph; Grimme, Stefan

    2017-08-30

    A fully quantum mechanical (QM) treatment to calculate electronic absorption (UV-vis) and circular dichroism (CD) spectra of typical biomolecules with thousands of atoms is presented. With our highly efficient sTDA-xTB method, spectra averaged along structures from molecular dynamics (MD) simulations can be computed in a reasonable time frame on standard desktop computers. This way, nonequilibrium structure and conformational, as well as purely quantum mechanical effects like charge-transfer or exciton-coupling, are included. Different from other contemporary approaches, the entire system is treated quantum mechanically and neither fragmentation nor system-specific adjustment is necessary. Among the systems considered are a large DNA fragment, oligopeptides, and even entire proteins in an implicit solvent. We propose the method in tandem with experimental spectroscopy or X-ray studies for the elucidation of complex (bio)molecular structures including metallo-proteins like myoglobin.

  17. XML-based approaches for the integration of heterogeneous bio-molecular data.

    Science.gov (United States)

    Mesiti, Marco; Jiménez-Ruiz, Ernesto; Sanz, Ismael; Berlanga-Llavori, Rafael; Perlasca, Paolo; Valentini, Giorgio; Manset, David

    2009-10-15

    The today's public database infrastructure spans a very large collection of heterogeneous biological data, opening new opportunities for molecular biology, bio-medical and bioinformatics research, but raising also new problems for their integration and computational processing. In this paper we survey the most interesting and novel approaches for the representation, integration and management of different kinds of biological data by exploiting XML and the related recommendations and approaches. Moreover, we present new and interesting cutting edge approaches for the appropriate management of heterogeneous biological data represented through XML. XML has succeeded in the integration of heterogeneous biomolecular information, and has established itself as the syntactic glue for biological data sources. Nevertheless, a large variety of XML-based data formats have been proposed, thus resulting in a difficult effective integration of bioinformatics data schemes. The adoption of a few semantic-rich standard formats is urgent to achieve a seamless integration of the current biological resources.

  18. Biomolecular characterization of diazotrophs isolated from the tropical soil in Malaysia.

    Science.gov (United States)

    Naher, Umme Aminun; Othman, Radziah; Latif, Mohammad Abdul; Panhwar, Qurban Ali; Amaddin, Puteri Aminatulhawa Megat; Shamsuddin, Zulkifli H

    2013-08-30

    This study was conducted to evaluate selected biomolecular characteristics of rice root-associated diazotrophs isolated from the Tanjong Karang rice irrigation project area of Malaysia. Soil and rice plant samples were collected from seven soil series belonging to order Inceptisol (USDA soil taxonomy). A total of 38 diazotrophs were isolated using a nitrogen-free medium. The biochemical properties of the isolated bacteria, such as nitrogenase activity, indoleacetic acid (IAA) production and sugar utilization, were measured. According to a cluster analysis of Jaccard's similarity coefficients, the genetic similarities among the isolated diazotrophs ranged from 10% to 100%. A dendogram constructed using the unweighted pair-group method with arithmetic mean (UPGMA) showed that the isolated diazotrophs clustered into 12 groups. The genomic DNA rep-PCR data were subjected to a principal component analysis, and the first four principal components (PC) accounted for 52.46% of the total variation among the 38 diazotrophs. The 10 diazotrophs that tested highly positive in the acetylene reduction assay (ARA) were identified as Bacillus spp. (9 diazotrophs) and Burkholderia sp. (Sb16) using the partial 16S rRNA gene sequence analysis. In the analysis of the biochemical characteristics, three principal components were accounted for approximately 85% of the total variation among the identified diazotrophs. The examination of root colonization using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) proved that two of the isolated diazotrophs (Sb16 and Sb26) were able to colonize the surface and interior of rice roots and fixed 22%-24% of the total tissue nitrogen from the atmosphere. In general, the tropical soils (Inceptisols) of the Tanjong Karang rice irrigation project area in Malaysia harbor a diverse group of diazotrophs that exhibit a large variation of biomolecular characteristics.

  19. Biomolecular Characterization of Diazotrophs Isolated from the Tropical Soil in Malaysia

    Directory of Open Access Journals (Sweden)

    Zulkifli H Shamsuddin

    2013-08-01

    Full Text Available This study was conducted to evaluate selected biomolecular characteristics of rice root-associated diazotrophs isolated from the Tanjong Karang rice irrigation project area of Malaysia. Soil and rice plant samples were collected from seven soil series belonging to order Inceptisol (USDA soil taxonomy. A total of 38 diazotrophs were isolated using a nitrogen-free medium. The biochemical properties of the isolated bacteria, such as nitrogenase activity, indoleacetic acid (IAA production and sugar utilization, were measured. According to a cluster analysis of Jaccard’s similarity coefficients, the genetic similarities among the isolated diazotrophs ranged from 10% to 100%. A dendogram constructed using the unweighted pair-group method with arithmetic mean (UPGMA showed that the isolated diazotrophs clustered into 12 groups. The genomic DNA rep-PCR data were subjected to a principal component analysis, and the first four principal components (PC accounted for 52.46% of the total variation among the 38 diazotrophs. The 10 diazotrophs that tested highly positive in the acetylene reduction assay (ARA were identified as Bacillus spp. (9 diazotrophs and Burkholderia sp. (Sb16 using the partial 16S rRNA gene sequence analysis. In the analysis of the biochemical characteristics, three principal components were accounted for approximately 85% of the total variation among the identified diazotrophs. The examination of root colonization using scanning electron microscopy (SEM and transmission electron microscopy (TEM proved that two of the isolated diazotrophs (Sb16 and Sb26 were able to colonize the surface and interior of rice roots and fixed 22%–24% of the total tissue nitrogen from the atmosphere. In general, the tropical soils (Inceptisols of the Tanjong Karang rice irrigation project area in Malaysia harbor a diverse group of diazotrophs that exhibit a large variation of biomolecular characteristics.

  20. A biomolecular recognition approach for the functionalization of cellulose with gold nanoparticles.

    Science.gov (United States)

    Almeida, A; Rosa, A M M; Azevedo, A M; Prazeres, D M F

    2017-09-01

    Materials with new and improved functionalities can be obtained by modifying cellulose with gold nanoparticles (AuNPs) via the in situ reduction of a gold precursor or the deposition or covalent immobilization of pre-synthesized AuNPs. Here, we present an alternative biomolecular recognition approach to functionalize cellulose with biotin-AuNPs that relies on a complex of 2 recognition elements: a ZZ-CBM3 fusion that combines a carbohydrate-binding module (CBM) with the ZZ fragment of the staphylococcal protein A and an anti-biotin antibody. Paper and cellulose microparticles with AuNPs immobilized via the ZZ-CBM3:anti-biotin IgG supramolecular complex displayed an intense red color, whereas essentially no color was detected when AuNPs were deposited over the unmodified materials. Scanning electron microscopy analysis revealed a homogeneous distribution of AuNPs when immobilized via ZZ-CBM3:anti-biotin IgG complexes and aggregation of AuNPs when deposited over paper, suggesting that color differences are due to interparticle plasmon coupling effects. The approach could be used to functionalize paper substrates and cellulose nanocrystals with AuNPs. More important, however, is the fact that the occurrence of a biomolecular recognition event between the CBM-immobilized antibody and its specific, AuNP-conjugated antigen is signaled by red color. This opens up the way for the development of simple and straightforward paper/cellulose-based tests where detection of a target analyte can be made by direct use of color signaling. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Versatile single-molecule multi-color excitation and detection fluorescence setup for studying biomolecular dynamics

    KAUST Repository

    Sobhy, M. A.

    2011-11-07

    Single-molecule fluorescence imaging is at the forefront of tools applied to study biomolecular dynamics both in vitro and in vivo. The ability of the single-molecule fluorescence microscope to conduct simultaneous multi-color excitation and detection is a key experimental feature that is under continuous development. In this paper, we describe in detail the design and the construction of a sophisticated and versatile multi-color excitation and emission fluorescence instrument for studying biomolecular dynamics at the single-molecule level. The setup is novel, economical and compact, where two inverted microscopes share a laser combiner module with six individual laser sources that extend from 400 to 640 nm. Nonetheless, each microscope can independently and in a flexible manner select the combinations, sequences, and intensities of the excitation wavelengths. This high flexibility is achieved by the replacement of conventional mechanical shutters with acousto-optic tunable filter (AOTF). The use of AOTF provides major advancement by controlling the intensities, duration, and selection of up to eight different wavelengths with microsecond alternation time in a transparent and easy manner for the end user. To our knowledge this is the first time AOTF is applied to wide-field total internal reflection fluorescence (TIRF) microscopy even though it has been commonly used in multi-wavelength confocal microscopy. The laser outputs from the combiner module are coupled to the microscopes by two sets of four single-mode optic fibers in order to allow for the optimization of the TIRF angle for each wavelength independently. The emission is split into two or four spectral channels to allow for the simultaneous detection of up to four different fluorophores of wide selection and using many possible excitation and photoactivation schemes. We demonstrate the performance of this new setup by conducting two-color alternating excitation single-molecule fluorescence resonance energy

  2. Monitoring the ordering in biomolecular films on vicinal silicon surfaces by reflectance difference/anisotropy spectroscopy

    Science.gov (United States)

    Silaghi, Simona D.; Zahn, Dietrich R. T.

    2006-05-01

    DNA base molecules, adenine, thymine, guanine, and cytosine may be employed as charge transport molecules in biomolecular electronic devices. Their electronic properties are comparable with those of inorganic wide bandgap materials, e.g. GaN with the absorption onset in the near ultra-violet (UV) range. A recent field effect transistor study based on a modified DNA base revealed that the prototype bio-transistor gives rise to a better voltage gain compared to one based on carbon nanotubes (CNTs) [G. Mauricio, P. Visconti, V. Arima, S. D'Amico, A. Biasco, E. D'Amone, R. Cingolani, R. Rinaldi, Nanoletters 3 (2003) 479]. Here, in situ reflectance difference/anisotropy spectroscopy (RDS/RAS) is employed under ultra-high vacuum (UHV) conditions for monitoring the growth of DNA base molecules on vicinal hydrogen passivated Si(1 1 1) surfaces. Such vicinal substrates consisting of steps and terraces may serves as suitable templates for molecular ordering. Indeed, RDS/RAS measurements reveal information about molecular ordering of DNA bases induced by the density of steps on silicon surfaces. All four molecules, however, behave differently on the vicinal substrates. The first transition dipole moments corresponding to adenine and thymine molecules align mainly perpendicular to the step edge direction while for guanine and cytosine they align parallel to this direction, however, only in very thin layers. The RDS/RAS signal of the guanine and cytosine layers with thicknesses above 20 nm saturates due to a loss of ordering at higher coverages. Additionally, time-resolved RDS/RAS measurements at the silicon E 2 (4.25 eV) critical point (CP) demonstrate the sensitivity to the biomolecular/inorganic interface formation.

  3. Versatile single-molecule multi-color excitation and detection fluorescence setup for studying biomolecular dynamics

    Science.gov (United States)

    Sobhy, M. A.; Elshenawy, M. M.; Takahashi, M.; Whitman, B. H.; Walter, N. G.; Hamdan, S. M.

    2011-11-01

    Single-molecule fluorescence imaging is at the forefront of tools applied to study biomolecular dynamics both in vitro and in vivo. The ability of the single-molecule fluorescence microscope to conduct simultaneous multi-color excitation and detection is a key experimental feature that is under continuous development. In this paper, we describe in detail the design and the construction of a sophisticated and versatile multi-color excitation and emission fluorescence instrument for studying biomolecular dynamics at the single-molecule level. The setup is novel, economical and compact, where two inverted microscopes share a laser combiner module with six individual laser sources that extend from 400 to 640 nm. Nonetheless, each microscope can independently and in a flexible manner select the combinations, sequences, and intensities of the excitation wavelengths. This high flexibility is achieved by the replacement of conventional mechanical shutters with acousto-optic tunable filter (AOTF). The use of AOTF provides major advancement by controlling the intensities, duration, and selection of up to eight different wavelengths with microsecond alternation time in a transparent and easy manner for the end user. To our knowledge this is the first time AOTF is applied to wide-field total internal reflection fluorescence (TIRF) microscopy even though it has been commonly used in multi-wavelength confocal microscopy. The laser outputs from the combiner module are coupled to the microscopes by two sets of four single-mode optic fibers in order to allow for the optimization of the TIRF angle for each wavelength independently. The emission is split into two or four spectral channels to allow for the simultaneous detection of up to four different fluorophores of wide selection and using many possible excitation and photoactivation schemes. We demonstrate the performance of this new setup by conducting two-color alternating excitation single-molecule fluorescence resonance energy

  4. Electrostatic solvation free energies of charged hard spheres using molecular dynamics with density functional theory interactions

    Energy Technology Data Exchange (ETDEWEB)

    Duignan, Timothy T. [Physical Science Division, Pacific Northwest National Laboratory, P.O. Box 999, Richland, Washington 99352, USA; Baer, Marcel D. [Physical Science Division, Pacific Northwest National Laboratory, P.O. Box 999, Richland, Washington 99352, USA; Schenter, Gregory K. [Physical Science Division, Pacific Northwest National Laboratory, P.O. Box 999, Richland, Washington 99352, USA; Mundy, Chistopher J. [Department of Chemical Engineering, University of Washington, Seattle, Washington 98185, USA

    2017-10-28

    Determining the solvation free energies of single ions in water is one of the most fundamental problems in physical chemistry and yet many unresolved questions remain. In particular, the ability to decompose the solvation free energy into simple and intuitive contributions will have important implications for coarse grained models of electrolyte solution. Here, we provide rigorous definitions of the various types of single ion solvation free energies based on different simulation protocols. We calculate solvation free energies of charged hard spheres using density functional theory interaction potentials with molecular dynamics simulation (DFT-MD) and isolate the effects of charge and cavitation, comparing to the Born (linear response) model. We show that using uncorrected Ewald summation leads to highly unphysical values for the solvation free energy and that charging free energies for cations are approximately linear as a function of charge but that there is a small non-linearity for small anions. The charge hydration asymmetry (CHA) for hard spheres, determined with quantum mechanics, is much larger than for the analogous real ions. This suggests that real ions, particularly anions, are significantly more complex than simple charged hard spheres, a commonly employed representation. We would like to thank Thomas Beck, Shawn Kathmann, Richard Remsing and John Weeks for helpful discussions. Computing resources were generously allocated by PNNL's Institutional Computing program. This research also used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. TTD, GKS, and CJM were supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences. MDB was supported by MS3 (Materials Synthesis and Simulation Across

  5. SAMPL4, a blind challenge for computational solvation free energies: the compounds considered

    Science.gov (United States)

    Guthrie, J. Peter

    2014-03-01

    For the fifth time I have provided a set of solvation energies (1 M gas to 1 M aqueous) for a SAMPL challenge. In this set there are 23 blind compounds and 30 supplementary compounds of related structure to one of the blind sets, but for which the solvation energy is readily available. The best current values of each compound are presented along with complete documentation of the experimental origins of the solvation energies. The calculations needed to go from reported data to solvation energies are presented, with particular attention to aspects which are new to this set. For some compounds the vapor pressures (VP) were reported for the liquid compound, which is solid at room temperature. To correct from VPsubcooled liquid to VPsublimation requires ΔSfusion, which is only known for mannitol. Estimated values were used for the others, all but one of which were benzene derivatives and expected to have very similar values. The final compound for which ΔSfusion was estimated was menthol, which melts at 42 °C so that modest errors in ΔSfusion will have little effect. It was also necessary to look into the effects of including estimated values of ΔCp on this correction. The approximate sizes of the effects of inclusion of ΔCp in the correction from VPsubcooled liquid to VPsublimation were estimated and it was noted that inclusion of ΔCp invariably makes ΔGS more positive. To extend the set of compounds for which the solvation energy could be calculated we explored the use of boiling point (b.p.) data from Reaxys/Beilstein as a substitute for studies of the VP as a function of temperature. B.p. data are not always reliable so it was necessary to develop a criterion for rejecting outliers. For two compounds (chlorinated guaiacols) it became clear that inclusion represented overreach; for each there were only two independent pressure, temperature points, which is too little for a trustworthy extrapolation. For a number of compounds the extrapolation from lowest

  6. Control of boiler temperature with explicit MPC; Panntemperaturreglering med explicit MPC

    Energy Technology Data Exchange (ETDEWEB)

    Slaetteke, Ola; Velut, Stefan; Raaberg, Martin

    2012-02-15

    MPC is the multivariable controller that has been most successful in the process industry and particularly the petrochemical industry. It has been described as one of the most significant developments in process control and the main reasons for this are: 1. It handles multivariable control problems in a natural manner. 2. It is relative easy to understand the structure of the controller, which is the same whether it is a simple loop or a multivariable system. 3. It handles limitations of both the process and other practical constraints in a systematic way. Examples of this is that a valve can only work between 0 and 100 %, but also that the CO-level in the flue gas must not exceed a certain level. 4. It allows for operating conditions near critical process boundaries, which in many cases is synonymous with increased production rates, reduced raw material consumption, better energy utilization, and faster process transitions. The aim of the project is to evaluate the potential of multivariable control in the form of explicit MPC in a boiler at Stora Enso Hylte Bruk. This research task can be divided into two sub-tasks: 1. General evaluation of explicit MPC. 2. Evaluation of multivariable control of boiler temperature The purpose of subtask one is to evaluate what is required of a facility owner to implement explicit MPC in a control system. This includes everything from available calculation tools, what is important to consider during the design phase of the controller, different pitfalls that exist, management of different operating modes, to how the controller should be implemented and commissioned. Subtask two is intended to evaluate the multivariable control of a boiler of CFB type (circulating fluidized bed). MPC controller will regulate the temperature in the boiler. In order to maintain the waste incineration directive, the temperature in the upper part of the boiler is controlled. This is done by means of changes in the flow of natural gas injection and

  7. Certain Verbs Are Syntactically Explicit Quantifiers

    Directory of Open Access Journals (Sweden)

    Anna Szabolcsi

    2010-12-01

    Full Text Available Quantification over individuals, times, and worlds can in principle be made explicit in the syntax of the object language, or left to the semantics and spelled out in the meta-language. The traditional view is that quantification over individuals is syntactically explicit, whereas quantification over times and worlds is not. But a growing body of literature proposes a uniform treatment. This paper examines the scopal interaction of aspectual raising verbs (begin, modals (can, and intensional raising verbs (threaten with quantificational subjects in Shupamem, Dutch, and English. It appears that aspectual raising verbs and at least modals may undergo the same kind of overt or covert scope-changing operations as nominal quantifiers; the case of intensional raising verbs is less clear. Scope interaction is thus shown to be a new potential diagnostic of object-linguistic quantification, and the similarity in the scope behavior of nominal and verbal quantifiers supports the grammatical plausibility of ontological symmetry, explored in Schlenker (2006.ReferencesBen-Shalom, D. 1996. Semantic Trees. Ph.D. thesis, UCLA.Bittner, M. 1993. Case, Scope, and Binding. Dordrecht: Reidel.Cresswell, M. 1990. Entities and Indices. Dordrecht: Kluwer.Cresti, D. 1995. ‘Extraction and reconstruction’. Natural Language Semantics 3: 79–122.http://dx.doi.org/10.1007/BF01252885Curry, B. H. & Feys, R. 1958. Combinatory Logic I. Dordrecht: North-Holland.Dowty, D. R. 1988. ‘Type raising, functional composition, and non-constituent conjunction’. In Richard T. Oehrle, Emmon W. Bach & Deirdre Wheeler (eds. ‘Categorial Grammars and Natural Language Structures’, 153–197. Dordrecht: Reidel.Fox, D. 2002. ‘TOn Logical Form’. In Randall Hendrick (ed. ‘Minimalist Syntax’, 82–124. Oxford: Blackwell.Gallin, D. 1975. Intensional and higher-order modal logic: with applications to Montague semantics. North Holland Pub. Co.; American Elsevier Pub. Co., Amsterdam

  8. Foldamer dynamics expressed via Markov state models. I. Explicit solvent molecular-dynamics simulations in acetonitrile, chloroform, methanol, and water

    Science.gov (United States)

    Elmer, Sidney P.; Park, Sanghyun; Pande, Vijay S.

    2005-09-01

    In this article, we analyze the folding dynamics of an all-atom model of a polyphenylacetylene (pPA) 12-mer in explicit solvent for four common organic and aqueous solvents: acetonitrile, chloroform, methanol, and water. The solvent quality has a dramatic effect on the time scales in which pPA 12-mers fold. Acetonitrile was found to manifest ideal folding conditions as suggested by optimal folding times on the order of ˜100-200ns, depending on temperature. In contrast, chloroform and water were observed to hinder the folding of the pPA 12-mer due to extreme solvation conditions relative to acetonitrile; chloroform denatures the oligomer, whereas water promotes aggregation and traps. The pPA 12-mer in a pure methanol solution folded in ˜400ns at 300K, compared relative to the experimental 12-mer folding time of ˜160ns measured in a 1:1 v/v THF/methanol solution. Requisite in drawing the aforementioned conclusions, analysis techniques based on Markov state models are applied to multiple short independent trajectories to extrapolate the long-time scale dynamics of the 12-mer in each respective solvent. We review the theory of Markov chains and derive a method to impose detailed balance on a transition-probability matrix computed from simulation data.

  9. Measuring Explicit Word Learning of Preschool Children: A Development Study.

    Science.gov (United States)

    Kelley, Elizabeth Spencer

    2017-08-15

    The purpose of this article is to present preliminary results related to the development of a new measure of explicit word learning. The measure incorporated elements of explicit vocabulary instruction and dynamic assessment and was designed to be sensitive to differences in word learning skill and to be feasible for use in clinical settings. The explicit word learning measure included brief teaching trials and repeated fine-grained measurement of semantic knowledge and production of 3 novel words (2 verbs and 1 adjective). Preschool children (N = 23) completed the measure of explicit word learning; standardized, norm-referenced measures of expressive and receptive vocabulary; and an incidental word learning task. The measure of explicit word learning provided meaningful information about word learning. Performance on the explicit measure was related to existing vocabulary knowledge and incidental word learning. Findings from this development study indicate that further examination of the measure of explicit word learning is warranted. The measure may have the potential to identify children who are poor word learners. https://doi.org/10.23641/asha.5170738.

  10. The effect of explicit financial incentives on physician behavior.

    Science.gov (United States)

    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.

  11. Explicit representation of confidence informs future value-based decisions

    DEFF Research Database (Denmark)

    Folke, Tomas; Jacobsen, Catrine; Fleming, Stephen M.

    2016-01-01

    follow a more consistent pattern (fewer transitivity violations). Finally, by tracking participants’ eye movements, we demonstrate that lower-level gaze dynamics can track uncertainty but do not directly impact changes of mind. These results suggest that an explicit and accurate representation......Humans can reflect on decisions and report variable levels of confidence. But why maintain an explicit representation of confidence for choices that have already been made and therefore cannot be undone? Here we show that an explicit representation of confidence is harnessed for subsequent changes...... of confidence has a positive impact on the quality of future value-based decisions....

  12. Explicit strong stability preserving multistep Runge–Kutta methods

    KAUST Repository

    Bresten, Christopher

    2015-10-15

    High-order spatial discretizations of hyperbolic PDEs are often designed to have strong stability properties, such as monotonicity. We study explicit multistep Runge-Kutta strong stability preserving (SSP) time integration methods for use with such discretizations. We prove an upper bound on the SSP coefficient of explicit multistep Runge-Kutta methods of order two and above. Numerical optimization is used to find optimized explicit methods of up to five steps, eight stages, and tenth order. These methods are tested on the linear advection and nonlinear Buckley-Leverett equations, and the results for the observed total variation diminishing and/or positivity preserving time-step are presented.

  13. Ab Initio Molecular Dynamics Simulation of the Phosphate Ion in Water: Insights into Solvation Shell Structure, Dynamics, and Kosmotropic Activity.

    Science.gov (United States)

    Sharma, Bikramjit; Chandra, Amalendu

    2017-11-22

    The structure and dynamics of solvation shells of the phosphate ion in deuterated water are studied by means of Born-Oppenheimer molecular dynamics simulation. The total number of molecules in the first and second solvation shells is found to be close to the effective hydration number reported experimentally. The OD bonds that are hydrogen bonded to the phosphate ion are found to be red shifted as compared to bulk water, which is consistent with experimental results. However, the two OD bonds of the same water molecule in the first hydration shell are found to be vibrationally distinct, which can be attributed to different strengths of the ion-water and water-water hydrogen bonds near the ion. Also, the hydrogen bonds formed by the second solvation shell OD bonds are somewhat stronger than the bulk. This finding shows a long ranged effect of the phosphate ion on water and also gives insights into the water structure making property of this anion. The dynamics of water in the first solvation shell is found to be significantly slower than that of the bulk. We have investigated the origin of the orientational slowing down of the first solvation shell water molecules and made connections to similar results observed experimentally.

  14. Structure of solvates of o-hydroxybenzoic acid in supercritical CO2-cosolvent media, according to molecular dynamics data

    Science.gov (United States)

    Petrenko, V. E.; Antipova, M. L.; Gurina, D. L.

    2015-03-01

    Three-component supercritical carbon dioxide-cosolvent (methanol, ethanol, water)- o-hydroxybenzoic acid ( o-HBA) mixtures at a density of 0.7 g/cm3 and temperatures of 318 and 348 K are simulated by means of molecular dynamics. The solvate structures are investigated. It is shown that the solvation mechanism of o-HBA (particularly the o-HBA molecule forming a stable solvate complex with one molecule of a cosolvent via a hydrogen bond through the carboxyl group) does not depend on the temperature or the cosolvent. It is noted that the form of the cosolvent in a supercritical fluid varies: alcohols are distributed in the bulk in the form of monomers and hydrogen-bonded dimers, and water molecules tend to form microclusters along with chained and spatially branched structures by means of hydrogen bonds. It is established that the local molar fraction of cosolvent around the solvate complexes grows. It is concluded that the solvation of o-HBA is determined by the behavior of cosolvent in media of supercritical CO2.

  15. Tibialis anterior muscle needle biopsy and sensitive biomolecular methods: a useful tool in myotonic dystrophy type 1

    Directory of Open Access Journals (Sweden)

    S. Iachettini

    2015-10-01

    Full Text Available Myotonic dystrophy type 1 (DM1 is a neuromuscular disorder caused by a CTG repeat expansion in 3’UTR of DMPK gene. This mutation causes accumulation of toxic RNA in nuclear foci leading to splicing misregulation of specific genes. In view of future clinical trials with antisense oligonucleotides in DM1 patients, it is important to set up sensitive and minimally-invasive tools to monitor the efficacy of treatments on skeletal muscle. A tibialis anterior (TA muscle sample of about 60 mg was obtained from 5 DM1 patients and 5 healthy subjects through a needle biopsy. A fragment of about 40 mg was used for histological examination and a fragment of about 20 mg was used for biomolecular analysis. The TA fragments obtained with the minimally-invasive needle biopsy technique is enough to perform all the histopathological and biomolecular evaluations useful to monitor a clinical trial on DM1 patients.

  16. Explicit Dynamic DDA Method considering Dynamic Contact Force

    National Research Council Canada - National Science Library

    Jian Zhao; Ming Xiao; Juntao Chen; Dongdong Li

    2016-01-01

      This paper proposes an explicit dynamic DDA method considering dynamic contact force, which aims at solving the problems of low efficiency of dynamic contact detection and the simulation of dynamic...

  17. Lightweight Solar Vehicle Impact Analysis Using ABAQUS/EXPLICIT

    National Research Council Canada - National Science Library

    Rossi Passarella; Zahari Taha

    2012-01-01

    Makalah ini menggambarkan the Abaqus/Explicit 6.7 simulasi performa kinerja untuk mempelajari dampak kondisi kecelakaan frontal untuk sebuah rancangan dan produksi struktur badan utama kendaraan ringan tenaga surya ringan rumahan...

  18. Optimal Explicit Binomial Confidence Interval with Guaranteed Coverage Probability

    OpenAIRE

    Chen, Xinjia

    2008-01-01

    In this paper, we develop an approach for optimizing the explicit binomial confidence interval recently derived by Chen et al. The optimization reduces conservativeness while guaranteeing prescribed coverage probability.

  19. Explicit Nonlinear Model Predictive Control Theory and Applications

    CERN Document Server

    Grancharova, Alexandra

    2012-01-01

    Nonlinear Model Predictive Control (NMPC) has become the accepted methodology to solve complex control problems related to process industries. The main motivation behind explicit NMPC is that an explicit state feedback law avoids the need for executing a numerical optimization algorithm in real time. The benefits of an explicit solution, in addition to the efficient on-line computations, include also verifiability of the implementation and the possibility to design embedded control systems with low software and hardware complexity. This book considers the multi-parametric Nonlinear Programming (mp-NLP) approaches to explicit approximate NMPC of constrained nonlinear systems, developed by the authors, as well as their applications to various NMPC problem formulations and several case studies. The following types of nonlinear systems are considered, resulting in different NMPC problem formulations: Ø  Nonlinear systems described by first-principles models and nonlinear systems described by black-box models; �...

  20. Study of the effect hydrogen binding in the solvation of alkaline earth cations with MeOH in nitromethane using 1 H NMR technique and determination of ionic solvation number

    CERN Document Server

    Alizadeh, N

    2001-01-01

    A proton NMR method for the study of the effect hydrogen binding and determination of solvation numbers of alkaline earth cations with methanol (MeOH) in in tromethane (NM) as diluent is described. The method is based on monitoring the resonance frequency of MeOH protons as a function of MeOH to metal ion mole ratio at constant metal ion concentration. the average solvation number of cation, n, at any MeOH/ metal ion mole ration was calculated from the NMR chemical shift-mole ration data and was plotted against the mole ration values. The solvation numbers of alkaline earth cations were obtained from the limiting values of the corresponding n, vs. mole ratio plots.

  1. Explicit and implicit reinforcement learning across the psychosis spectrum.

    Science.gov (United States)

    Barch, Deanna M; Carter, Cameron S; Gold, James M; Johnson, Sheri L; Kring, Ann M; MacDonald, Angus W; Pizzagalli, Diego A; Ragland, J Daniel; Silverstein, Steven M; Strauss, Milton E

    2017-07-01

    Motivational and hedonic impairments are core features of a variety of types of psychopathology. An important aspect of motivational function is reinforcement learning (RL), including implicit (i.e., outside of conscious awareness) and explicit (i.e., including explicit representations about potential reward associations) learning, as well as both positive reinforcement (learning about actions that lead to reward) and punishment (learning to avoid actions that lead to loss). Here we present data from paradigms designed to assess both positive and negative components of both implicit and explicit RL, examine performance on each of these tasks among individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis, and examine their relative relationships to specific symptom domains transdiagnostically. None of the diagnostic groups differed significantly from controls on the implicit RL tasks in either bias toward a rewarded response or bias away from a punished response. However, on the explicit RL task, both the individuals with schizophrenia and schizoaffective disorder performed significantly worse than controls, but the individuals with bipolar did not. Worse performance on the explicit RL task, but not the implicit RL task, was related to worse motivation and pleasure symptoms across all diagnostic categories. Performance on explicit RL, but not implicit RL, was related to working memory, which accounted for some of the diagnostic group differences. However, working memory did not account for the relationship of explicit RL to motivation and pleasure symptoms. These findings suggest transdiagnostic relationships across the spectrum of psychotic disorders between motivation and pleasure impairments and explicit RL. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  2. A shortcut for IMEX methods: integrate the residual explicitly

    OpenAIRE

    Rodrigues, Savio B.

    2017-01-01

    In numerical time-integration with implicit-explicit (IMEX) methods, a within-step adaptable decomposition called residual balanced decomposition is introduced. This decomposition allows any residual occurring in the implicit equation of the implicit-step to be moved into the explicit part of the decomposition. By balancing the residual, the accuracy of the local truncation error of the time-stepping method becomes independent from the accuracy by which the implicit equation is solved. In thi...

  3. Explicit signal to noise ratio in reproducing kernel Hilbert spaces

    DEFF Research Database (Denmark)

    Gomez-Chova, Luis; Nielsen, Allan Aasbjerg; Camps-Valls, Gustavo

    2011-01-01

    an alternative kernel MNF (KMNF) in which the noise is explicitly estimated in the reproducing kernel Hilbert space. This enables KMNF dealing with non-linear relations between the noise and the signal features jointly. Results show that the proposed KMNF provides the most noise-free features when confronted...... with PCA, MNF, KPCA, and the previous version of KMNF. Extracted features with the explicit KMNF also improve hyperspectral image classification....

  4. Recent Advances in Explicit Multiparametric Nonlinear Model Predictive Control

    KAUST Repository

    Domínguez, Luis F.

    2011-01-19

    In this paper we present recent advances in multiparametric nonlinear programming (mp-NLP) algorithms for explicit nonlinear model predictive control (mp-NMPC). Three mp-NLP algorithms for NMPC are discussed, based on which novel mp-NMPC controllers are derived. The performance of the explicit controllers are then tested and compared in a simulation example involving the operation of a continuous stirred-tank reactor (CSTR). © 2010 American Chemical Society.

  5. Biomolecular Interaction Analysis Using an Optical Surface Plasmon Resonance Biosensor: The Marquardt Algorithm vs Newton Iteration Algorithm.

    Science.gov (United States)

    Hu, Jiandong; Ma, Liuzheng; Wang, Shun; Yang, Jianming; Chang, Keke; Hu, Xinran; Sun, Xiaohui; Chen, Ruipeng; Jiang, Min; Zhu, Juanhua; Zhao, Yuanyuan

    2015-01-01

    Kinetic analysis of biomolecular interactions are powerfully used to quantify the binding kinetic constants for the determination of a complex formed or dissociated within a given time span. Surface plasmon resonance biosensors provide an essential approach in the analysis of the biomolecular interactions including the interaction process of antigen-antibody and receptors-ligand. The binding affinity of the antibody to the antigen (or the receptor to the ligand) reflects the biological activities of the control antibodies (or receptors) and the corresponding immune signal responses in the pathologic process. Moreover, both the association rate and dissociation rate of the receptor to ligand are the substantial parameters for the study of signal transmission between cells. A number of experimental data may lead to complicated real-time curves that do not fit well to the kinetic model. This paper presented an analysis approach of biomolecular interactions established by utilizing the Marquardt algorithm. This algorithm was intensively considered to implement in the homemade bioanalyzer to perform the nonlinear curve-fitting of the association and disassociation process of the receptor to ligand. Compared with the results from the Newton iteration algorithm, it shows that the Marquardt algorithm does not only reduce the dependence of the initial value to avoid the divergence but also can greatly reduce the iterative regression times. The association and dissociation rate constants, ka, kd and the affinity parameters for the biomolecular interaction, KA, KD, were experimentally obtained 6.969×10(5) mL·g(-1)·s(-1), 0.00073 s(-1), 9.5466×10(8) mL·g(-1) and 1.0475×10(-9) g·mL(-1), respectively from the injection of the HBsAg solution with the concentration of 16 ng·mL(-1). The kinetic constants were evaluated distinctly by using the obtained data from the curve-fitting results.

  6. Cybersex: regulating sexually explicit expression on the Internet.

    Science.gov (United States)

    Cate, F H

    1996-01-01

    While the First Amendment restricts the power of the government to control access by adults to sexually explicit expression that is not obscene, the government may restrict access by children, provided that those restrictions do not limit adults to reading only "what is fit for children." Controlling access by children presents special problems in the context of broadcasting, because broadcast programming is accessible to children too young to read and because of the impossibility of segregating adults and children in the audience. The Supreme Court therefore permits the government to require "channeling" of sexually explicit programming to times when fewer unsupervised children are in the audience, to facilitate parental control over children's access to sexually explicit material. Although Internet content includes less than one percent of sexually explicit expression, that material has been the subject of intensive media and government attention. Much of that attention ignores (1) the high level of constitutional protection applicable to non-obscene, sexually explicit expression; (2) features of the Internet which facilitate controlling access by children to sexually explicit expression far more effectively than in broadcasting or print media; and (3) the First Amendment values served by permitting expression of all forms on the Internet.

  7. Detection of Ammonia and Phosphine Gas using Heterojunction Biomolecular Chain with Multilayer GaAs Nanopore Electrode

    Directory of Open Access Journals (Sweden)

    Debarati Dey

    2017-01-01

    Full Text Available This paper presents Density Functional Theory and Non-Equilibrium Green’s Function based First Principles calculations to explore the sensing property of Adenine and Thymine based hetero-junction chins for Ammonia and Phosphine gas molecules. This modeling and simulation technique plays an important and crucial role in the fast growing semiconductor based nanotechnology field. The hetero-junction chain has been passed through the multi layer GaAs nanopore electrodes. It has been found that Current-Voltage characteristics of the bio-molecular chain highly depend during the foreign gas molecules adsorption. This Current-Voltage sensitivity has been raised upto 40 and 9.3 times with the presence of single Ammonia and Phosphine molecules respectively under the ultra low bias voltage application. Adsorption of single molecule Ammonia and Phosphine increases the conductivity of the heterogeneous bio-molecular chain at room temperature. The quantum ballistic transmission through the direct band gap semi-conductor material GaAs nanopore increases during the Ammonia and Phosphine gas adsorption by the heterogeneous chain. In this paper we attempt to present the molecular model sensor with circuit elements. The attractive potential of conductivity modulation suggests this heterogeneous bio-molecular chain as an application in future generation bio-sensor technology.

  8. miRNAs Plasma Profiles in Vascular Dementia: Biomolecular Data and Biomedical Implications

    Science.gov (United States)

    Ragusa, Marco; Bosco, Paolo; Tamburello, Lucia; Barbagallo, Cristina; Condorelli, Angelo G.; Tornitore, Mariangela; Spada, Rosario S.; Barbagallo, Davide; Scalia, Marina; Elia, Maurizio; Di Pietro, Cinzia; Purrello, Michele

    2016-01-01

    Vascular dementia (VaD) is a pathogenetically heterogeneous neuropsychiatric syndrome, mainly characterized by cognitive impairment. Among dementias, it is second by incidence after Alzheimer’s dementia (AD). VaD biomolecular bases have been poorly characterized, but vascular-linked factors affecting the CNS and its functions are generally hypothesized to perform a major role, together with cardiovascular and immunological factors. miRNAs, which perform critically important biomolecular roles within cell networks, are also found in biological fluids as circulating miRNAs (cmiRNAs). We hypothesized that differentially expressed (DE) cmiRNAs in plasma from VaD patients could be applied to diagnose VaD through liquid biopsies; these profiles also could allow to start investigating VaD molecular bases. By exploiting TaqMan Low-Density Arrays and single TaqMan assays, miR-10b*, miR29a-3p, and miR-130b-3p were discovered and validated as significantly downregulated DE cmiRNAs in VaD patients compared to unaffected controls (NCs). These miRNAs also were found to be significantly downregulated in a matched cohort of AD patients, but miR-130b-3p levels were lower in AD than in VaD. A negative correlation was detected between miR-29a and miR-130b expression and cognitive impairment in VaD and AD, respectively. Receiver operating characteristic curves demonstrated that decreased plasma levels of miR-10b*, miR29a-3p, and miR-130b-3p allow to discriminate VaD and AD patients from NCs. Furthermore, the concurrent downregulation of both miR-10b* and miR-130b-3p in VaD showed an area under the curve (AUC) of 0.789 (p < 0.0001) with 75% of sensitivity and 72% of specificity, whereas an AUC of 0.789 (p < 0.0001) with 92% of sensitivity and 81% of specificity was found for both in AD. The miRNAs profiles reported in this paper pave the way to translational applications to molecular VaD diagnosis, but they also should allow to further investigate on its molecular bases. PMID

  9. Hierarchical Biomolecular Emulsions Using 3-D Microfluidics with Uniform Surface Chemistry.

    Science.gov (United States)

    Toprakcioglu, Zenon; Levin, Aviad; Knowles, Tuomas P J

    2017-11-13

    Microfluidic devices can be used to produce single, double and higher order emulsions, where droplet sizes can be precisely controlled and modulated. Such emulsions have great potential for the storage and study of biomolecules, including peptides and proteins. However, advancement of this technique has remained challenging due to the tendency of various biomolecules to adhere to the surface of the formed channels, resulting in changes in surface wetting and fouling on the micrometer scale. Thus, precise control of surface wettability plays a crucial role in the processes that govern droplet formation. Here, we report an approach for producing both water-oil-water (w/o/w) and oil-water-oil (o/w/o) double emulsions without any need for surface modification, an enabling feature for biomolecular encapsulation. Using this strategy, we show that the number of monodisperse encapsulated internal droplets can be controlled systematically and reproducibly by suitable adjustment of the relevant flow rates, and ranges from 1 to 40 in the case of w/o/w emulsions. We further demonstrate that the number of internal droplets scales linearly with the reciprocal flow rate of the outer continuous phase, when the inner and middle phase flow rates are kept constant. We demonstrate that this approach is suitable for forming double emulsions where the inner phase consists of reconstituted silk protein solution whereby incubation of the internal droplets can be induced to form a gel resulting in silk fibroin microgels surrounded by an external oil shell. Finally, for o/w/o emulsions, we show that single or multiple monodisperse internal droplets can be encapsulated with a size that ranges over 1 order of magnitude, from ca. 10 μm to >100 μm. Moreover, o/w/o emulsions where the middle phase consists of silk fibroin solution were prepared and by allowing the protein to aggregate, a core-shell structure was formed. This microfluidic strategy allows for multiple emulsions to be generated

  10. Solubility prediction, solvate and cocrystal screening as tools for rational crystal engineering.

    Science.gov (United States)

    Loschen, Christoph; Klamt, Andreas

    2015-06-01

    The fact that novel drug candidates are becoming increasingly insoluble is a major problem of current drug development. Computational tools may address this issue by screening for suitable solvents or by identifying potential novel cocrystal formers that increase bioavailability. In contrast to other more specialized methods, the fluid phase thermodynamics approach COSMO-RS (conductor-like screening model for real solvents) allows for a comprehensive treatment of drug solubility, solvate and cocrystal formation and many other thermodynamics properties in liquids. This article gives an overview of recent COSMO-RS developments that are of interest for drug development and contains several new application examples for solubility prediction and solvate/cocrystal screening. For all property predictions COSMO-RS has been used. The basic concept of COSMO-RS consists of using the screening charge density as computed from first principles calculations in combination with fast statistical thermodynamics to compute the chemical potential of a compound in solution. The fast and accurate assessment of drug solubility and the identification of suitable solvents, solvate or cocrystal formers is nowadays possible and may be used to complement modern drug development. Efficiency is increased by avoiding costly quantum-chemical computations using a database of previously computed molecular fragments. COSMO-RS theory can be applied to a range of physico-chemical properties, which are of interest in rational crystal engineering. Most notably, in combination with experimental reference data, accurate quantitative solubility predictions in any solvent or solvent mixture are possible. Additionally, COSMO-RS can be extended to the prediction of cocrystal formation, which results in considerable predictive accuracy concerning coformer screening. In a recent variant costly quantum chemical calculations are avoided resulting in a significant speed-up and ease-of-use. © 2015 Royal

  11. On the Modeling of Polar Component of Solvation Energy using Smooth Gaussian-Based Dielectric Function.

    Science.gov (United States)

    Li, Lin; Li, Chuan; Alexov, Emil

    2014-05-01

    Traditional implicit methods for modeling electrostatics in biomolecules use a two-dielectric approach: a biomolecule is assigned low dielectric constant while the water phase is considered as a high dielectric constant medium. However, such an approach treats the biomolecule-water interface as a sharp dielectric border between two homogeneous dielectric media and does not account for inhomogeneous dielectric properties of the macromolecule as well. Recently we reported a new development, a smooth Gaussian-based dielectric function which treats the entire system, the solute and the water phase, as inhomogeneous dielectric medium (J Chem Theory Comput. 2013 Apr 9; 9(4): 2126-2136.). Here we examine various aspects of the modeling of polar solvation energy in such inhomogeneous systems in terms of the solute-water boundary and the inhomogeneity of the solute in the absence of water surrounding. The smooth Gaussian-based dielectric function is implemented in the DelPhi finite-difference program, and therefore the sensitivity of the results with respect to the grid parameters is investigated, and it is shown that the calculated polar solvation energy is almost grid independent. Furthermore, the results are compared with the standard two-media model and it is demonstrated that on average, the standard method overestimates the magnitude of the polar solvation energy by a factor 2.5. Lastly, the possibility of the solute to have local dielectric constant larger than of a bulk water is investigated in a benchmarking test against experimentally determined set of pKa's and it is speculated that side chain rearrangements could result in local dielectric constant larger than 80.

  12. Use of the FACTS solvation model for protein-ligand docking calculations. Application to EADock.

    Science.gov (United States)

    Zoete, Vincent; Grosdidier, Aurélien; Cuendet, Michel; Michielin, Olivier

    2010-01-01

    Protein-ligand docking has made important progress during the last decade and has become a powerful tool for drug development, opening the way to virtual high throughput screening and in silico structure-based ligand design. Despite the flattering picture that has been drawn, recent publications have shown that the docking problem is far from being solved, and that more developments are still needed to achieve high successful prediction rates and accuracy. Introducing an accurate description of the solvation effect upon binding is thought to be essential to achieve this goal. In particular, EADock uses the Generalized Born Molecular Volume 2 (GBMV2) solvent model, which has been shown to reproduce accurately the desolvation energies calculated by solving the Poisson equation. Here, the implementation of the Fast Analytical Continuum Treatment of Solvation (FACTS) as an implicit solvation model in small molecules docking calculations has been assessed using the EADock docking program. Our results strongly support the use of FACTS for docking. The success rates of EADock/FACTS and EADock/GBMV2 are similar, i.e. around 75% for local docking and 65% for blind docking. However, these results come at a much lower computational cost: FACTS is 10 times faster than GBMV2 in calculating the total electrostatic energy, and allows a speed up of EADock by a factor of 4. This study also supports the EADock development strategy relying on the CHARMM package for energy calculations, which enables straightforward implementation and testing of the latest developments in the field of Molecular Modeling.

  13. Origin of diverse time scales in the protein hydration layer solvation dynamics: A simulation study

    Science.gov (United States)

    Mondal, Sayantan; Mukherjee, Saumyak; Bagchi, Biman

    2017-10-01

    In order to inquire the microscopic origin of observed multiple time scales in solvation dynamics, we carry out several computer experiments. We perform atomistic molecular dynamics simulations on three protein-water systems, namely, lysozyme, myoglobin, and sweet protein monellin. In these experiments, we mutate the charges of the neighbouring amino acid side chains of certain natural probes (tryptophan) and also freeze the side chain motions. In order to distinguish between different contributions, we decompose the total solvation energy response in terms of various components present in the system. This allows us to capture the interplay among different self- and cross-energy correlation terms. Freezing the protein motions removes the slowest component that results from side chain fluctuations, but a part of slowness remains. This leads to the conclusion that the slow component approximately in the 20-80 ps range arises from slow water molecules present in the hydration layer. While the more than 100 ps component has multiple origins, namely, adjacent charges in amino acid side chains, hydrogen bonded water molecules and a dynamically coupled motion between side chain and water. In addition, the charges enforce a structural ordering of nearby water molecules and helps to form a local long-lived hydrogen bonded network. Further separation of the spatial and temporal responses in solvation dynamics reveals different roles of hydration and bulk water. We find that the hydration layer water molecules are largely responsible for the slow component, whereas the initial ultrafast decay arises predominantly (approximately 80%) due to the bulk. This agrees with earlier theoretical observations. We also attempt to rationalise our results with the help of a molecular hydrodynamic theory that was developed using classical time dependent density functional theory in a semi-quantitative manner.

  14. A Comparison of Predictive Thermo and Water Solvation Property Prediction Tools and Experimental Data for Selected Traditional Chemical Warfare Agents and Simulants II: COSMO RS and COSMOTherm

    Science.gov (United States)

    2017-04-01

    A COMPARISON OF PREDICTIVE THERMO AND WATER SOLVATION PROPERTY PREDICTION TOOLS AND EXPERIMENTAL DATA FOR...4. TITLE AND SUBTITLE A Comparison of Predictive Thermo and Water Solvation Property Prediction Tools and Experimental Data for Selected...ambient temperature. We then directed these descriptions of each molecule to COSMOTherm to calculate boiling point, vapor pressure, water solubility

  15. Mapping the Free Energy of Lithium Solvation in the Protic Ionic Liquid Ethylammonuim Nitrate: A Metadynamics Study.

    Science.gov (United States)

    Kachmar, Ali; Carignano, Marcelo; Laino, Teodoro; Iannuzzi, Marcella; Hutter, Jürg

    2017-08-10

    Understanding lithium solvation and transport in ionic liquids is important due to their possible application in electrochemical devices. Using first-principles simulations aided by a metadynamics approach we study the free-energy landscape for lithium ions at infinite dilution in ethylammonium nitrate, a protic ionic liquid. We analyze the local structure of the liquid around the lithium cation and obtain a quantitative picture in agreement with experimental findings. Our simulations show that the lowest two free energy minima correspond to conformations with the lithium ion being solvated either by three or four nitrate ions with a transition barrier between them of 0.2 eV. Other less probable conformations having different solvation pattern are also investigated. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Photo-illuminated diamond as a solid-state source of solvated electrons in water for nitrogen reduction.

    Science.gov (United States)

    Zhu, Di; Zhang, Linghong; Ruther, Rose E; Hamers, Robert J

    2013-09-01

    The photocatalytic reduction of N₂ to NH₃ is typically hampered by poor binding of N₂ to catalytic materials and by the very high energy of the intermediates involved in this reaction. Solvated electrons directly introduced into the reactant solution can provide an alternative pathway to overcome such limitations. Here we demonstrate that illuminated hydrogen-terminated diamond yields facile electron emission into water, thus inducing reduction of N₂ to NH₃ at ambient temperature and pressure. Transient absorption measurements at 632 nm reveal the presence of solvated electrons adjacent to the diamond after photoexcitation. Experiments using inexpensive synthetic diamond samples and diamond powder show that photocatalytic activity is strongly dependent on the surface termination and correlates with the production of solvated electrons. The use of diamond to eject electrons into a reactant liquid represents a new paradigm for photocatalytic reduction, bringing electrons directly to reactants without requiring molecular adsorption to the surface.

  17. Importance of the solvation degree of peptide-resin beads for amine groups determination by the picric acid method

    Directory of Open Access Journals (Sweden)

    Cilli Eduardo M.

    2000-01-01

    Full Text Available The classic and important picric acid method used in polymers biochemical and chemical fields of polymers for amine group quantification was chosen in this work as a model for evaluating the influence of the resin bead solvation during an analytical procedure. It was observed that this method, proposed almost three decades ago, failed to quantify amine groups of peptidyl-resin containing aggregating and polar sequence. This was due to inefficient solvation of resin beads when only CH2Cl2 was used for picrate anion binding and subsequent washing steps. It was demonstrated that the use of CH2Cl2/DMF (dimethylformamide and CH2Cl2/EtOH solutions during these steps allows correct determination of peptidyl-resin amine groups. Besides the importance for the solid phase peptide synthesis methodology itself, these findings also represent the first quantitative demonstration of the relationship between solvation degree and the efficiency of a polymer-supported analytical method.

  18. Fast Domain Decomposition Algorithm for Continuum Solvation Models: Energy and First Derivatives.

    Science.gov (United States)

    Lipparini, Filippo; Stamm, Benjamin; Cancès, Eric; Maday, Yvon; Mennucci, Benedetta

    2013-08-13

    In this contribution, an efficient, parallel, linear scaling implementation of the conductor-like screening model (COSMO) is presented, following the domain decomposition (dd) algorithm recently proposed by three of us. The implementation is detailed and its linear scaling properties, both in computational cost and memory requirements, are demonstrated. Such behavior is also confirmed by several numerical examples on linear and globular large-sized systems, for which the calculation of the energy and of the forces is achieved with timings compatible with the use of polarizable continuum solvation for molecular dynamics simulations.

  19. Preferential solvation, ion pairing, and dynamics of concentrated aqueous solutions of divalent metal nitrate salts

    Science.gov (United States)

    Yadav, Sushma; Chandra, Amalendu

    2017-12-01

    We have investigated the characteristics of preferential solvation of ions, structure of solvation shells, ion pairing, and dynamics of aqueous solutions of divalent alkaline-earth metal nitrate salts at varying concentration by means of molecular dynamics simulations. Hydration shell structures and the extent of preferential solvation of the metal and nitrate ions in the solutions are investigated through calculations of radial distribution functions, tetrahedral ordering, and also spatial distribution functions. The Mg2+ ions are found to form solvent separated ion-pairs while the Ca2+ and Sr2+ ions form contact ion pairs with the nitrate ions. These findings are further corroborated by excess coordination numbers calculated through Kirkwood-Buff G factors for different ion-ion and ion-water pairs. The ion-pairing propensity is found to be in the order of Mg(NO3) 2 coefficients. It is found that proper modeling of these solutions requires the inclusion of electronic polarization of the ions which is achieved in the current study through electronic continuum correction force fields. A detailed analysis of the effects of ion-pairs on the structure and dynamics of water around the hydrated ions is done through classification of water into different subspecies based on their locations around the cations or anions only or bridged between them. We have looked at the diffusion coefficients, relaxation of orientational correlation functions, and also the residence times of different subspecies of water to explore the dynamics of water in different structural environments in the solutions. The current results show that the water molecules are incorporated into fairly well-structured hydration shells of the ions, thus decreasing the single-particle diffusivities and increasing the orientational relaxation times of water with an increase in salt concentration. The different structural motifs also lead to the presence of substantial dynamical heterogeneity in these solutions

  20. Dynamic Processes in Prochiral Solvating Agents (pro-CSAs Studied by NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Jan Labuta

    2014-05-01

    Full Text Available Several dynamic processes, including tautomerism and macrocyclic inversion, in 1H-NMR prochiral solvating agents (pro-CSAs are investigated. Various features of pro-CSA, including modes of interaction for complex formation, stoichiometry, binding strength and temperature effects were compared for three representative pro-CSA molecules. Structural effects of conjugated tetrapyrrole pro-CSA on the mechanism of enantiomeric excess determination are also discussed. Detailed analysis of species (complexes and dynamic processes occurring in solution and their 1H-NMR spectral manifestations at various temperatures is presented.