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Sample records for amber biomolecular simulation

  1. The Amber Biomolecular Simulation Programs

    PubMed Central

    CASE, DAVID A.; CHEATHAM, THOMAS E.; DARDEN, TOM; GOHLKE, HOLGER; LUO, RAY; MERZ, KENNETH M.; ONUFRIEV, ALEXEY; SIMMERLING, CARLOS; WANG, BING; WOODS, ROBERT J.

    2006-01-01

    We describe the development, current features, and some directions for future development of the Amber package of computer programs. This package evolved from a program that was constructed in the late 1970s to do Assisted Model Building with Energy Refinement, and now contains a group of programs embodying a number of powerful tools of modern computational chemistry, focused on molecular dynamics and free energy calculations of proteins, nucleic acids, and carbohydrates. PMID:16200636

  2. Introduction. Biomolecular simulation

    PubMed Central

    Mulholland, Adrian J.

    2008-01-01

    ‘Everything that living things do can be understood in terms of the jigglings and wigglings of atoms’ as Richard Feynman provocatively stated nearly 50 years ago. But how can we ‘see’ this wiggling and jiggling and understand how it drives biology? Increasingly, computer simulations of biological macromolecules are helping to meet this challenge. PMID:18826912

  3. LIPID11: a modular framework for lipid simulations using amber.

    PubMed

    Skjevik, Åge A; Madej, Benjamin D; Walker, Ross C; Teigen, Knut

    2012-09-13

    Accurate simulation of complex lipid bilayers has long been a goal in condensed phase molecular dynamics (MD). Structure and function of membrane-bound proteins are highly dependent on the lipid bilayer environment and are challenging to study through experimental methods. Within Amber, there has been limited focus on lipid simulations, although some success has been seen with the use of the General Amber Force Field (GAFF). However, to date there are no dedicated Amber lipid force fields. In this paper we describe a new charge derivation strategy for lipids consistent with the Amber RESP approach and a new atom and residue naming and type convention. In the first instance, we have combined this approach with GAFF parameters. The result is LIPID11, a flexible, modular framework for the simulation of lipids that is fully compatible with the existing Amber force fields. The charge derivation procedure, capping strategy, and nomenclature for LIPID11, along with preliminary simulation results and a discussion of the planned long-term parameter development are presented here. Our findings suggest that LIPID11 is a modular framework feasible for phospholipids and a flexible starting point for the development of a comprehensive, Amber-compatible lipid force field. PMID:22916730

  4. Exploring Biomolecular Recognition by Modeling and Simulation

    NASA Astrophysics Data System (ADS)

    Wade, Rebecca

    2007-12-01

    Biomolecular recognition is complex. The balance between the different molecular properties that contribute to molecular recognition, such as shape, electrostatics, dynamics and entropy, varies from case to case. This, along with the extent of experimental characterization, influences the choice of appropriate computational approaches to study biomolecular interactions. I will present computational studies in which we aim to make concerted use of bioinformatics, biochemical network modeling and molecular simulation techniques to study protein-protein and protein-small molecule interactions and to facilitate computer-aided drug design.

  5. CHARMM: The Biomolecular Simulation Program

    PubMed Central

    Brooks, B.R.; Brooks, C.L.; MacKerell, A.D.; Nilsson, L.; Petrella, R.J.; Roux, B.; Won, Y.; Archontis, G.; Bartels, C.; Boresch, S.; Caflisch, A.; Caves, L.; Cui, Q.; Dinner, A.R.; Feig, M.; Fischer, S.; Gao, J.; Hodoscek, M.; Im, W.; Kuczera, K.; Lazaridis, T.; Ma, J.; Ovchinnikov, V.; Paci, E.; Pastor, R.W.; Post, C.B.; Pu, J.Z.; Schaefer, M.; Tidor, B.; Venable, R. M.; Woodcock, H. L.; Wu, X.; Yang, W.; York, D.M.; Karplus, M.

    2009-01-01

    CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estimators, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. In addition, the CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numerous platforms in both serial and parallel architectures. This paper provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM paper in 1983. PMID:19444816

  6. Data Intensive Analysis of Biomolecular Simulations

    SciTech Connect

    Straatsma, TP

    2008-03-01

    The advances in biomolecular modeling and simulation made possible by the availability of increasingly powerful high performance computing resources is extending molecular simulations to biological more relevant system size and time scales. At the same time, advances in simulation methodologies are allowing more complex processes to be described more accurately. These developments make a systems approach to computational structural biology feasible, but this will require a focused emphasis on the comparative analysis of the increasing number of molecular simulations that are being carried out for biomolecular systems with more realistic models, multi-component environments, and for longer simulation times. Just as in the case of the analysis of the large data sources created by the new high-throughput experimental technologies, biomolecular computer simulations contribute to the progress in biology through comparative analysis. The continuing increase in available protein structures allows the comparative analysis of the role of structure and conformational flexibility in protein function, and is the foundation of the discipline of structural bioinformatics. This creates the opportunity to derive general findings from the comparative analysis of molecular dynamics simulations of a wide range of proteins, protein-protein complexes and other complex biological systems. Because of the importance of protein conformational dynamics for protein function, it is essential that the analysis of molecular trajectories is carried out using a novel, more integrative and systematic approach. We are developing a much needed rigorous computer science based framework for the efficient analysis of the increasingly large data sets resulting from molecular simulations. Such a suite of capabilities will also provide the required tools for access and analysis of a distributed library of generated trajectories. Our research is focusing on the following areas: (1) the development of an

  7. Data Intensive Analysis of Biomolecular Simulations

    SciTech Connect

    Straatsma, TP; Soares, Thereza A.

    2007-12-01

    The advances in biomolecular modeling and simulation made possible by the availability of increasingly powerful high performance computing resources is extending molecular simulations to biological more relevant system size and time scales. At the same time, advances in simulation methodologies are allowing more complex processes to be described more accurately. These developments make a systems approach to computational structural biology feasible, but this will require a focused emphasis on the comparative analysis of the increasing number of molecular simulations that are being carried out for biomolecular systems with more realistic models, multi-component environments, and for longer simulation times. Just as in the case of the analysis of the large data sources created by the new high-throughput experimental technologies, biomolecular computer simulations contribute to the progress in biology through comparative analysis. The continuing increase in available protein structures allows the comparative analysis of the role of structure and conformational flexibility in protein function, and is the foundation of the discipline of structural bioinformatics. This creates the opportunity to derive general findings from the comparative analysis of molecular dynamics simulations of a wide range of proteins, protein-protein complexes and other complex biological systems. Because of the importance of protein conformational dynamics for protein function, it is essential that the analysis of molecular trajectories is carried out using a novel, more integrative and systematic approach. We are developing a much needed rigorous computer science based framework for the efficient analysis of the increasingly large data sets resulting from molecular simulations. Such a suite of capabilities will also provide the required tools for access and analysis of a distributed library of generated trajectories. Our research is focusing on the following areas: (1) the development of an

  8. Charge Group Partitioning in Biomolecular Simulation

    PubMed Central

    Canzar, Stefan; El-Kebir, Mohammed; Pool, René; Elbassioni, Khaled; Mark, Alan E.; Geerke, Daan P.; Stougie, Leen; Klau, Gunnar W.

    2013-01-01

    Abstract Molecular simulation techniques are increasingly being used to study biomolecular systems at an atomic level. Such simulations rely on empirical force fields to represent the intermolecular interactions. There are many different force fields available—each based on a different set of assumptions and thus requiring different parametrization procedures. Recently, efforts have been made to fully automate the assignment of force-field parameters, including atomic partial charges, for novel molecules. In this work, we focus on a problem arising in the automated parametrization of molecules for use in combination with the gromos family of force fields: namely, the assignment of atoms to charge groups such that for every charge group the sum of the partial charges is ideally equal to its formal charge. In addition, charge groups are required to have size at most k. We show \\documentclass{aastex}\\usepackage{amsbsy}\\usepackage{amsfonts}\\usepackage{amssymb}\\usepackage{bm}\\usepackage{mathrsfs}\\usepackage{pifont}\\usepackage{stmaryrd}\\usepackage{textcomp}\\usepackage{portland, xspace}\\usepackage{amsmath, amsxtra}\\pagestyle{empty}\\DeclareMathSizes{10}{9}{7}{6}\\begin{document}$${ \\cal N P}$$\\end{document}-hardness and give an exact algorithm that solves practical problem instances to provable optimality in a fraction of a second. PMID:23461571

  9. Simulation of biomolecular diffusion and complex formation.

    PubMed Central

    Allison, S A; Northrup, S H; McCammon, J A

    1986-01-01

    Diffusion is a phenomenon of very widespread importance in molecular biophysics. Diffusion can determine the rates and character of the assembly of multisubunit structures, the binding of ligands to receptors, and the internal motions of molecules and assemblies that involve solvent surface displacements. Current computer simulation techniques provide much more detailed descriptions of diffusional processes than have been available in the past. Models can be constructed to include such realistic features as structural subunits at the submolecular level (domains, monomers, or atoms); detailed electrostatic charge distributions and corresponding solvent-screened inter- and intramolecular interactions; and hydrodynamic interactions. The trajectories can be analyzed either to provide direct information on biomolecular function (e.g., the bimolecular rate constant for formation of an electron-transfer complex between two proteins), or to provide or test models for the interpretation of experimental data (e.g., the time dependence of fluorescence depolarization for segments of DNA). Here, we first review the theory of diffusional simulations, with special emphasis on new techniques such as those for obtaining transport properties of flexible assemblies and rate constants of diffusion-controlled reactions. Then we survey a variety of recent applications, including studies of large-scale motion in DNA segments and substrate "steering" in enzyme-substrate binding. We conclude with a discussion of current work (e.g., formation of protein complexes) and possible areas for future work. PMID:3955168

  10. iBIOMES Lite: Summarizing Biomolecular Simulation Data in Limited Settings

    PubMed Central

    2015-01-01

    As the amount of data generated by biomolecular simulations dramatically increases, new tools need to be developed to help manage this data at the individual investigator or small research group level. In this paper, we introduce iBIOMES Lite, a lightweight tool for biomolecular simulation data indexing and summarization. The main goal of iBIOMES Lite is to provide a simple interface to summarize computational experiments in a setting where the user might have limited privileges and limited access to IT resources. A command-line interface allows the user to summarize, publish, and search local simulation data sets. Published data sets are accessible via static hypertext markup language (HTML) pages that summarize the simulation protocols and also display data analysis graphically. The publication process is customized via extensible markup language (XML) descriptors while the HTML summary template is customized through extensible stylesheet language (XSL). iBIOMES Lite was tested on different platforms and at several national computing centers using various data sets generated through classical and quantum molecular dynamics, quantum chemistry, and QM/MM. The associated parsers currently support AMBER, GROMACS, Gaussian, and NWChem data set publication. The code is available at https://github.com/jcvthibault/ibiomes. PMID:24830957

  11. iBIOMES Lite: summarizing biomolecular simulation data in limited settings.

    PubMed

    Thibault, Julien C; Cheatham, Thomas E; Facelli, Julio C

    2014-06-23

    As the amount of data generated by biomolecular simulations dramatically increases, new tools need to be developed to help manage this data at the individual investigator or small research group level. In this paper, we introduce iBIOMES Lite, a lightweight tool for biomolecular simulation data indexing and summarization. The main goal of iBIOMES Lite is to provide a simple interface to summarize computational experiments in a setting where the user might have limited privileges and limited access to IT resources. A command-line interface allows the user to summarize, publish, and search local simulation data sets. Published data sets are accessible via static hypertext markup language (HTML) pages that summarize the simulation protocols and also display data analysis graphically. The publication process is customized via extensible markup language (XML) descriptors while the HTML summary template is customized through extensible stylesheet language (XSL). iBIOMES Lite was tested on different platforms and at several national computing centers using various data sets generated through classical and quantum molecular dynamics, quantum chemistry, and QM/MM. The associated parsers currently support AMBER, GROMACS, Gaussian, and NWChem data set publication. The code is available at https://github.com/jcvthibault/ibiomes . PMID:24830957

  12. The power of coarse graining in biomolecular simulations

    PubMed Central

    Ingólfsson, Helgi I; Lopez, Cesar A; Uusitalo, Jaakko J; de Jong, Djurre H; Gopal, Srinivasa M; Periole, Xavier; Marrink, Siewert J

    2014-01-01

    Computational modeling of biological systems is challenging because of the multitude of spatial and temporal scales involved. Replacing atomistic detail with lower resolution, coarse grained (CG), beads has opened the way to simulate large-scale biomolecular processes on time scales inaccessible to all-atom models. We provide an overview of some of the more popular CG models used in biomolecular applications to date, focusing on models that retain chemical specificity. A few state-of-the-art examples of protein folding, membrane protein gating and self-assembly, DNA hybridization, and modeling of carbohydrate fibers are used to illustrate the power and diversity of current CG modeling. PMID:25309628

  13. Improved model of hydrated calcium ion for molecular dynamics simulations using classical biomolecular force fields.

    PubMed

    Yoo, Jejoong; Wilson, James; Aksimentiev, Aleksei

    2016-10-01

    Calcium ions (Ca(2+) ) play key roles in various fundamental biological processes such as cell signaling and brain function. Molecular dynamics (MD) simulations have been used to study such interactions, however, the accuracy of the Ca(2+) models provided by the standard MD force fields has not been rigorously tested. Here, we assess the performance of the Ca(2+) models from the most popular classical force fields AMBER and CHARMM by computing the osmotic pressure of model compounds and the free energy of DNA-DNA interactions. In the simulations performed using the two standard models, Ca(2+) ions are seen to form artificial clusters with chloride, acetate, and phosphate species; the osmotic pressure of CaAc2 and CaCl2 solutions is a small fraction of the experimental values for both force fields. Using the standard parameterization of Ca(2+) ions in the simulations of Ca(2+) -mediated DNA-DNA interactions leads to qualitatively wrong outcomes: both AMBER and CHARMM simulations suggest strong inter-DNA attraction whereas, in experiment, DNA molecules repel one another. The artificial attraction of Ca(2+) to DNA phosphate is strong enough to affect the direction of the electric field-driven translocation of DNA through a solid-state nanopore. To address these shortcomings of the standard Ca(2+) model, we introduce a custom model of a hydrated Ca(2+) ion and show that using our model brings the results of the above MD simulations in quantitative agreement with experiment. Our improved model of Ca(2+) can be readily applied to MD simulations of various biomolecular systems, including nucleic acids, proteins and lipid bilayer membranes. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 752-763, 2016. PMID:27144470

  14. An Analysis of Biomolecular Force Fields for Simulations of Polyglutamine in Solution.

    PubMed

    Fluitt, Aaron M; de Pablo, Juan J

    2015-09-01

    Polyglutamine (polyQ) peptides are a useful model system for biophysical studies of protein folding and aggregation, both for their intriguing aggregation properties and their own relevance to human disease. The genetic expansion of a polyQ tract triggers the formation of amyloid aggregates associated with nine neurodegenerative diseases. Several clearly identifiable and separable factors, notably the length of the polyQ tract, influence the mechanism of aggregation, its associated kinetics, and the ensemble of structures formed. Atomistic simulations are well positioned to answer open questions regarding the thermodynamics and kinetics of polyQ folding and aggregation. The additional, explicit representation of water permits deeper investigation of the role of solvent dynamics, and it permits a direct comparison of simulation results with infrared spectroscopy experiments. The generation of meaningful simulation results hinges on satisfying two essential criteria: achieving sufficient conformational sampling to draw statistically valid conclusions, and accurately reproducing the intermolecular forces that govern system structure and dynamics. In this work, we examine the ability of 12 biomolecular force fields to reproduce the properties of a simple, 30-residue polyQ peptide (Q30) in explicit water. In addition to secondary and tertiary structure, we consider generic structural properties of polymers that provide additional dimensions for analysis of the highly degenerate disordered states of the molecule. We find that the 12 force fields produce a wide range of predictions. We identify AMBER ff99SB, AMBER ff99SB*, and OPLS-AA/L to be most suitable for studies of polyQ folding and aggregation. PMID:26331258

  15. An Analysis of Biomolecular Force Fields for Simulations of Polyglutamine in Solution

    SciTech Connect

    Fluitt, Aaron M.; de Pablo, Juan J.

    2015-09-01

    Polyglutamine (polyQ) peptides are a useful model system for biophysical studies of protein folding and aggregation, both for their intriguing aggregation properties and their own relevance to human disease. The genetic expansion of a polyQ tract triggers the formation of amyloid aggregates associated with nine neurodegenerative diseases. Several clearly identifiable and separable factors, notably the length of the polyQ tract, influence the mechanism of aggregation, its associated kinetics, and the ensemble of structures formed. Atomistic simulations are well positioned to answer open questions regarding the thermodynamics and kinetics of polyQ folding and aggregation. The additional, explicit representation of water permits deeper investigation of the role of solvent dynamics, and it permits a direct comparison of simulation results with infrared spectroscopy experiments. The generation of meaningful simulation results hinges on satisfying two essential criteria: achieving sufficient conformational sampling to draw statistically valid conclusions, and accurately reproducing the intermolecular forces that govern system structure and dynamics. In this work, we examine the ability of 12 biomolecular force fields to reproduce the properties of a simple, 30-residue polyQ peptide (Q30) in explicit water. In addition to secondary and tertiary structure, we consider generic structural properties of polymers that provide additional dimensions for analysis of the highly degenerate disordered states of the molecule. We find that the 12 force fields produce a wide range of predictions. We identify AMBER ff99SB, AMBER ff99SB*, and OPLS-AA/L to be most suitable for studies of polyQ folding and aggregation.

  16. An Analysis of Biomolecular Force Fields for Simulations of Polyglutamine in Solution

    PubMed Central

    Fluitt, Aaron M.; de Pablo, Juan J.

    2015-01-01

    Polyglutamine (polyQ) peptides are a useful model system for biophysical studies of protein folding and aggregation, both for their intriguing aggregation properties and their own relevance to human disease. The genetic expansion of a polyQ tract triggers the formation of amyloid aggregates associated with nine neurodegenerative diseases. Several clearly identifiable and separable factors, notably the length of the polyQ tract, influence the mechanism of aggregation, its associated kinetics, and the ensemble of structures formed. Atomistic simulations are well positioned to answer open questions regarding the thermodynamics and kinetics of polyQ folding and aggregation. The additional, explicit representation of water permits deeper investigation of the role of solvent dynamics, and it permits a direct comparison of simulation results with infrared spectroscopy experiments. The generation of meaningful simulation results hinges on satisfying two essential criteria: achieving sufficient conformational sampling to draw statistically valid conclusions, and accurately reproducing the intermolecular forces that govern system structure and dynamics. In this work, we examine the ability of 12 biomolecular force fields to reproduce the properties of a simple, 30-residue polyQ peptide (Q30) in explicit water. In addition to secondary and tertiary structure, we consider generic structural properties of polymers that provide additional dimensions for analysis of the highly degenerate disordered states of the molecule. We find that the 12 force fields produce a wide range of predictions. We identify AMBER ff99SB, AMBER ff99SB∗, and OPLS-AA/L to be most suitable for studies of polyQ folding and aggregation. PMID:26331258

  17. Using FPGA Devices to Accelerate Biomolecular Simulations

    SciTech Connect

    Alam, Sadaf R; Agarwal, Pratul K; Smith, Melissa C; Vetter, Jeffrey S; Caliga, David E

    2007-03-01

    A field-programmable gate array implementation of the particle-mesh Ewald a molecular dynamics simulation method reduces the microprocessor time-to-solution by a factor of three while using only high-level languages. The application speedup on FPGA devices increases with the problem size. The authors use a performance model to analyze the potential of simulating large-scale biological systems faster than many cluster-based supercomputing platforms.

  18. Energy Efficient Biomolecular Simulations with FPGA-based Reconfigurable Computing

    SciTech Connect

    Hampton, Scott S; Agarwal, Pratul K

    2010-05-01

    Reconfigurable computing (RC) is being investigated as a hardware solution for improving time-to-solution for biomolecular simulations. A number of popular molecular dynamics (MD) codes are used to study various aspects of biomolecules. These codes are now capable of simulating nanosecond time-scale trajectories per day on conventional microprocessor-based hardware, but biomolecular processes often occur at the microsecond time-scale or longer. A wide gap exists between the desired and achievable simulation capability; therefore, there is considerable interest in alternative algorithms and hardware for improving the time-to-solution of MD codes. The fine-grain parallelism provided by Field Programmable Gate Arrays (FPGA) combined with their low power consumption make them an attractive solution for improving the performance of MD simulations. In this work, we use an FPGA-based coprocessor to accelerate the compute-intensive calculations of LAMMPS, a popular MD code, achieving up to 5.5 fold speed-up on the non-bonded force computations of the particle mesh Ewald method and up to 2.2 fold speed-up in overall time-to-solution, and potentially an increase by a factor of 9 in power-performance efficiencies for the pair-wise computations. The results presented here provide an example of the multi-faceted benefits to an application in a heterogeneous computing environment.

  19. Biomolecular Simulation of Base Excision Repair and Protein Signaling

    SciTech Connect

    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.

  20. New functionalities in the GROMOS biomolecular simulation software.

    PubMed

    Kunz, Anna-Pitschna E; Allison, Jane R; Geerke, Daan P; Horta, Bruno A C; Hünenberger, Philippe H; Riniker, Sereina; Schmid, Nathan; van Gunsteren, Wilfred F

    2012-01-30

    Since the most recent description of the functionalities of the GROMOS software for biomolecular simulation in 2005 many new functions have been implemented. In this article, the new functionalities that involve modified forces in a molecular dynamics (MD) simulation are described: the treatment of electronic polarizability, an implicit surface area and internal volume solvation term to calculate interatomic forces, functions for the GROMOS coarse-grained supramolecular force field, a multiplicative switching function for nonbonded interactions, adiabatic decoupling of a number of degrees of freedom with temperature or force scaling to enhance sampling, and nonequilibrium MD to calculate the dielectric permittivity or viscosity. Examples that illustrate the use of these functionalities are given. PMID:22076815

  1. Stochastic Simulation of Biomolecular Networks in Dynamic Environments.

    PubMed

    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. PMID:27248512

  2. Stochastic Simulation of Biomolecular Networks in Dynamic Environments

    PubMed Central

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

    2016-01-01

    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. PMID:27248512

  3. An extensible interface for QM/MM molecular dynamics simulations with AMBER

    PubMed Central

    Götz, Andreas W.; Clark, Matthew A.; Walker, Ross C.

    2014-01-01

    We present an extensible interface between the AMBER molecular dynamics (MD) software package and electronic structure software packages for quantum mechanical (QM) and mixed QM and classical molecular mechanical (MM) MD simulations within both mechanical and electronic embedding schemes. With this interface, ab initio wave function theory and density functional theory methods, as available in the supported electronic structure software packages, become available for QM/MM MD simulations with AMBER. The interface has been written in a modular fashion that allows straight forward extensions to support additional QM software packages and can easily be ported to other MD software. Data exchange between the MD and QM software is implemented by means of files and system calls or the message passing interface standard. Based on extensive tests, default settings for the supported QM packages are provided such that energy is conserved for typical QM/MM MD simulations in the microcanonical ensemble. Results for the free energy of binding of calcium ions to aspartate in aqueous solution comparing semiempirical and density functional Hamiltonians are shown to demonstrate features of this interface. PMID:24122798

  4. Towards an accurate representation of electrostatics in classical force fields: Efficient implementation of multipolar interactions in biomolecular simulations

    NASA Astrophysics Data System (ADS)

    Sagui, Celeste; Pedersen, Lee G.; Darden, Thomas A.

    2004-01-01

    The accurate simulation of biologically active macromolecules faces serious limitations that originate in the treatment of electrostatics in the empirical force fields. The current use of "partial charges" is a significant source of errors, since these vary widely with different conformations. By contrast, the molecular electrostatic potential (MEP) obtained through the use of a distributed multipole moment description, has been shown to converge to the quantum MEP outside the van der Waals surface, when higher order multipoles are used. However, in spite of the considerable improvement to the representation of the electronic cloud, higher order multipoles are not part of current classical biomolecular force fields due to the excessive computational cost. In this paper we present an efficient formalism for the treatment of higher order multipoles in Cartesian tensor formalism. The Ewald "direct sum" is evaluated through a McMurchie-Davidson formalism [L. McMurchie and E. Davidson, J. Comput. Phys. 26, 218 (1978)]. The "reciprocal sum" has been implemented in three different ways: using an Ewald scheme, a particle mesh Ewald (PME) method, and a multigrid-based approach. We find that even though the use of the McMurchie-Davidson formalism considerably reduces the cost of the calculation with respect to the standard matrix implementation of multipole interactions, the calculation in direct space remains expensive. When most of the calculation is moved to reciprocal space via the PME method, the cost of a calculation where all multipolar interactions (up to hexadecapole-hexadecapole) are included is only about 8.5 times more expensive than a regular AMBER 7 [D. A. Pearlman et al., Comput. Phys. Commun. 91, 1 (1995)] implementation with only charge-charge interactions. The multigrid implementation is slower but shows very promising results for parallelization. It provides a natural way to interface with continuous, Gaussian-based electrostatics in the future. It is

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

    PubMed

    Thibault, J C; Roe, D R; Eilbeck, K; Cheatham Iii, 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. PMID:26387907

  6. Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 1. Generalized Born

    PubMed Central

    2012-01-01

    We present an implementation of generalized Born implicit solvent all-atom classical molecular dynamics (MD) within the AMBER program package that runs entirely on CUDA enabled NVIDIA graphics processing units (GPUs). We discuss the algorithms that are used to exploit the processing power of the GPUs and show the performance that can be achieved in comparison to simulations on conventional CPU clusters. The implementation supports three different precision models in which the contributions to the forces are calculated in single precision floating point arithmetic but accumulated in double precision (SPDP), or everything is computed in single precision (SPSP) or double precision (DPDP). In addition to performance, we have focused on understanding the implications of the different precision models on the outcome of implicit solvent MD simulations. We show results for a range of tests including the accuracy of single point force evaluations and energy conservation as well as structural properties pertainining to protein dynamics. The numerical noise due to rounding errors within the SPSP precision model is sufficiently large to lead to an accumulation of errors which can result in unphysical trajectories for long time scale simulations. We recommend the use of the mixed-precision SPDP model since the numerical results obtained are comparable with those of the full double precision DPDP model and the reference double precision CPU implementation but at significantly reduced computational cost. Our implementation provides performance for GB simulations on a single desktop that is on par with, and in some cases exceeds, that of traditional supercomputers. PMID:22582031

  7. iBIOMES: managing and sharing biomolecular simulation data in a distributed environment.

    PubMed

    Thibault, Julien C; Facelli, Julio C; Cheatham, Thomas E

    2013-03-25

    Biomolecular simulations, which were once batch queue or compute limited, have now become data analysis and management limited. In this paper we introduce a new management system for large biomolecular simulation and computational chemistry data sets. The system can be easily deployed on distributed servers to create a mini-grid at the researcher's site. The system not only offers a simple data deposition mechanism but also a way to register data into the system without moving the data from their original location. Any registered data set can be searched and downloaded using a set of defined metadata for molecular dynamics and quantum mechanics and visualized through a dynamic Web interface. PMID:23413948

  8. Design and application of implicit solvent models in biomolecular simulations

    PubMed Central

    Kleinjung, Jens; Fraternali, Franca

    2014-01-01

    We review implicit solvent models and their parametrisation by introducing the concepts and recent devlopments of the most popular models with a focus on parametrisation via force matching. An overview of recent applications of the solvation energy term in protein dynamics, modelling, design and prediction is given to illustrate the usability and versatility of implicit solvation in reproducing the physical behaviour of biomolecular systems. Limitations of implicit modes are discussed through the example of more challenging systems like nucleic acids and membranes. PMID:24841242

  9. Exploring accurate Poisson–Boltzmann methods for biomolecular simulations

    PubMed Central

    Wang, Changhao; Wang, Jun; Cai, Qin; Li, Zhilin; Zhao, Hong-Kai; Luo, Ray

    2013-01-01

    Accurate and efficient treatment of electrostatics is a crucial step in computational analyses of biomolecular structures and dynamics. In this study, we have explored a second-order finite-difference numerical method to solve the widely used Poisson–Boltzmann equation for electrostatic analyses of realistic bio-molecules. The so-called immersed interface method was first validated and found to be consistent with the classical weighted harmonic averaging method for a diversified set of test biomolecules. The numerical accuracy and convergence behaviors of the new method were next analyzed in its computation of numerical reaction field grid potentials, energies, and atomic solvation forces. Overall similar convergence behaviors were observed as those by the classical method. Interestingly, the new method was found to deliver more accurate and better-converged grid potentials than the classical method on or nearby the molecular surface, though the numerical advantage of the new method is reduced when grid potentials are extrapolated to the molecular surface. Our exploratory study indicates the need for further improving interpolation/extrapolation schemes in addition to the developments of higher-order numerical methods that have attracted most attention in the field. PMID:24443709

  10. Data for molecular dynamics simulations of B-type cytochrome c oxidase with the Amber force field.

    PubMed

    Yang, Longhua; Skjevik, Åge A; Han Du, Wen-Ge; Noodleman, Louis; Walker, Ross C; Götz, Andreas W

    2016-09-01

    Cytochrome c oxidase (CcO) is a vital enzyme that catalyzes the reduction of molecular oxygen to water and pumps protons across mitochondrial and bacterial membranes. This article presents parameters for the cofactors of ba3-type CcO that are compatible with the all-atom Amber ff12SB and ff14SB force fields. Specifically, parameters were developed for the CuA pair, heme b, and the dinuclear center that consists of heme a3 and CuB bridged by a hydroperoxo group. The data includes geometries in XYZ coordinate format for cluster models that were employed to compute proton transfer energies and derive bond parameters and point charges for the force field using density functional theory. Also included are the final parameter files that can be employed with the Amber leap program to generate input files for molecular dynamics simulations with the Amber software package. Based on the high resolution (1.8 Å) X-ray crystal structure of the ba3-type CcO from Thermus thermophilus (Protein Data Bank ID number PDB: 3S8F), we built a model that is embedded in a POPC lipid bilayer membrane and solvated with TIP3P water molecules and counterions. We provide PDB data files of the initial model and the equilibrated model that can be used for further studies. PMID:27547799

  11. Data model, dictionaries, and desiderata for biomolecular simulation data indexing and sharing

    PubMed Central

    2014-01-01

    Background Few environments have been developed or deployed to widely share biomolecular simulation data or to enable collaborative networks to facilitate data exploration and reuse. As the amount and complexity of data generated by these simulations is dramatically increasing and the methods are being more widely applied, the need for new tools to manage and share this data has become obvious. In this paper we present the results of a process aimed at assessing the needs of the community for data representation standards to guide the implementation of future repositories for biomolecular simulations. Results We introduce a list of common data elements, inspired by previous work, and updated according to feedback from the community collected through a survey and personal interviews. These data elements integrate the concepts for multiple types of computational methods, including quantum chemistry and molecular dynamics. The identified core data elements were organized into a logical model to guide the design of new databases and application programming interfaces. Finally a set of dictionaries was implemented to be used via SQL queries or locally via a Java API built upon the Apache Lucene text-search engine. Conclusions The model and its associated dictionaries provide a simple yet rich representation of the concepts related to biomolecular simulations, which should guide future developments of repositories and more complex terminologies and ontologies. The model still remains extensible through the decomposition of virtual experiments into tasks and parameter sets, and via the use of extended attributes. The benefits of a common logical model for biomolecular simulations was illustrated through various use cases, including data storage, indexing, and presentation. All the models and dictionaries introduced in this paper are available for download at http://ibiomes.chpc.utah.edu/mediawiki/index.php/Downloads. PMID:24484917

  12. Equipartition and the Calculation of Temperature in Biomolecular Simulations.

    PubMed

    Eastwood, Michael P; Stafford, Kate A; Lippert, Ross A; Jensen, Morten Ø; Maragakis, Paul; Predescu, Cristian; Dror, Ron O; Shaw, David E

    2010-07-13

    Since the behavior of biomolecules can be sensitive to temperature, the ability to accurately calculate and control the temperature in molecular dynamics (MD) simulations is important. Standard analysis of equilibrium MD simulations-even constant-energy simulations with negligible long-term energy drift-often yields different calculated temperatures for different motions, however, in apparent violation of the statistical mechanical principle of equipartition of energy. Although such analysis provides a valuable warning that other simulation artifacts may exist, it leaves the actual value of the temperature uncertain. We observe that Tolman's generalized equipartition theorem should hold for long stable simulations performed using velocity-Verlet or other symplectic integrators, because the simulated trajectory is thought to sample almost exactly from a continuous trajectory generated by a shadow Hamiltonian. From this we conclude that all motions should share a single simulation temperature, and we provide a new temperature estimator that we test numerically in simulations of a diatomic fluid and of a solvated protein. Apparent temperature variations between different motions observed using standard estimators do indeed disappear when using the new estimator. We use our estimator to better understand how thermostats and barostats can exacerbate integration errors. In particular, we find that with large (albeit widely used) time steps, the common practice of using two thermostats to remedy so-called hot solvent-cold solute problems can have the counterintuitive effect of causing temperature imbalances. Our results, moreover, highlight the utility of multiple-time step integrators for accurate and efficient simulation. PMID:26615934

  13. Strike a Balance: Optimization of Backbone Torsion Parameters of AMBER Polarizable Force Field for Simulations of Proteins and Peptides

    PubMed Central

    WANG, ZHI-XIANG; ZHANG, WEI; WU, CHUN; LEI, HONGXING; CIEPLAK, PIOTR; DUAN, YONG

    2014-01-01

    Based on the AMBER polarizable model (ff02), we have reoptimized the parameters related to the main-chain (Φ, Ψ) torsion angles by fitting to the Boltzmann-weighted average quantum mechanical (QM) energies of the important regions (i.e., β, PII, αR, and αL regions). Following the naming convention of the AMBER force field series, this release will be called ff02pol.rl The force field has been assessed both by energetic comparison against the QM data and by the replica exchange molecular dynamics simulations of short alanine peptides in water. For Ace-Ala-Nme, the simulated populations in the β, PII and αR regions were approximately 30, 43, and 26%, respectively. For Ace-(Ala)7-Nme, the populations in these three regions were approximately 24, 49, and 26%. Both were in qualitative agreement with the NMR and CD experimental conclusions. In comparison with the previous force field, ff02pol.rl demonstrated good balance among these three important regions. The optimized torsion parameters, together with those in ff02, allow us to carry out simulations on proteins and peptides with the consideration of polarization. PMID:16526038

  14. An improved simple polarisable water model for use in biomolecular simulation

    SciTech Connect

    Bachmann, Stephan J.; Gunsteren, Wilfred F. van

    2014-12-14

    The accuracy of biomolecular simulations depends to some degree on the accuracy of the water model used to solvate the biomolecules. Because many biomolecules such as proteins are electrostatically rather inhomogeneous, containing apolar, polar, and charged moieties or side chains, a water model should be able to represent the polarisation response to a local electrostatic field, while being compatible with the force field used to model the biomolecules or protein. The two polarisable water models, COS/G2 and COS/D, that are compatible with the GROMOS biomolecular force fields leave room for improvement. The COS/G2 model has a slightly too large dielectric permittivity and the COS/D model displays a much too slow dynamics. The proposed COS/D2 model has four interaction sites: only one Lennard-Jones interaction site, the oxygen atom, and three permanent charge sites, the two hydrogens, and one massless off-atom site that also serves as charge-on-spring (COS) polarisable site with a damped or sub-linear dependence of the induced dipole on the electric field strength for large values of the latter. These properties make it a cheap and yet realistic water model for biomolecular solvation.

  15. PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations

    PubMed Central

    Dolinsky, Todd J.; Czodrowski, Paul; Li, Hui; Nielsen, Jens E.; Jensen, Jan H.; Klebe, Gerhard; Baker, Nathan A.

    2007-01-01

    Real-world observable physical and chemical characteristics are increasingly being calculated from the 3D structures of biomolecules. Methods for calculating pKa values, binding constants of ligands, and changes in protein stability are readily available, but often the limiting step in computational biology is the conversion of PDB structures into formats ready for use with biomolecular simulation software. The continued sophistication and integration of biomolecular simulation methods for systems- and genome-wide studies requires a fast, robust, physically realistic and standardized protocol for preparing macromolecular structures for biophysical algorithms. As described previously, the PDB2PQR web server addresses this need for electrostatic field calculations (Dolinsky et al., Nucleic Acids Research, 32, W665–W667, 2004). Here we report the significantly expanded PDB2PQR that includes the following features: robust standalone command line support, improved pKa estimation via the PROPKA framework, ligand parameterization via PEOE_PB charge methodology, expanded set of force fields and easily incorporated user-defined parameters via XML input files, and improvement of atom addition and optimization code. These features are available through a new web interface (http://pdb2pqr.sourceforge.net/), which offers users a wide range of options for PDB file conversion, modification and parameterization. PMID:17488841

  16. Dynamical fingerprints for probing individual relaxation processes in biomolecular dynamics with simulations and kinetic experiments

    SciTech Connect

    Noe, F; Diadone, Isabella; Lollmann, Marc; Sauer, Marcus; Chondera, John D; Smith, Jeremy C

    2011-01-01

    There is a gap between kinetic experiment and simulation in their views of the dynamics of complex biomolecular systems. Whereas experiments typically reveal only a few readily discernible exponential relaxations, simulations often indicate complex multistate behavior. Here, a theoretical framework is presented that reconciles these two approaches. The central concept is dynamical fingerprints which contain peaks at the time scales of the dynamical processes involved with amplitudes determined by the experimental observable. Fingerprints can be generated from both experimental and simulation data, and their comparison by matching peaks permits assignment of structural changes present in the simulation to experimentally observed relaxation processes. The approach is applied here to a test case interpreting single molecule fluorescence correlation spectroscopy experiments on a set of fluorescent peptides with molecular dynamics simulations. The peptides exhibit complex kinetics shown to be consistent with the apparent simplicity of the experimental data. Moreover, the fingerprint approach can be used to design new experiments with site-specific labels that optimally probe specific dynamical processes in the molecule under investigation.

  17. Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations.

    PubMed

    Takada, Shoji; Kanada, Ryo; Tan, Cheng; Terakawa, Tsuyoshi; Li, Wenfei; Kenzaki, Hiroo

    2015-12-15

    Due to hierarchic nature of biomolecular systems, their computational modeling calls for multiscale approaches, in which coarse-grained (CG) simulations are used to address long-time dynamics of large systems. Here, we review recent developments and applications of CG modeling methods, focusing on our methods primarily for proteins, DNA, and their complexes. These methods have been implemented in the CG biomolecular simulator, CafeMol. Our CG model has resolution such that ∼10 non-hydrogen atoms are grouped into one CG particle on average. For proteins, each amino acid is represented by one CG particle. For DNA, one nucleotide is simplified by three CG particles, representing sugar, phosphate, and base. The protein modeling is based on the idea that proteins have a globally funnel-like energy landscape, which is encoded in the structure-based potential energy function. We first describe two representative minimal models of proteins, called the elastic network model and the classic Go̅ model. We then present a more elaborate protein model, which extends the minimal model to incorporate sequence and context dependent local flexibility and nonlocal contacts. For DNA, we describe a model developed by de Pablo's group that was tuned to well reproduce sequence-dependent structural and thermodynamic experimental data for single- and double-stranded DNAs. Protein-DNA interactions are modeled either by the structure-based term for specific cases or by electrostatic and excluded volume terms for nonspecific cases. We also discuss the time scale mapping in CG molecular dynamics simulations. While the apparent single time step of our CGMD is about 10 times larger than that in the fully atomistic molecular dynamics for small-scale dynamics, large-scale motions can be further accelerated by two-orders of magnitude with the use of CG model and a low friction constant in Langevin dynamics. Next, we present four examples of applications. First, the classic Go̅ model was used to

  18. Evaluation of Emerging Energy-Efficient Heterogeneous Computing Platforms for Biomolecular and Cellular Simulation Workloads

    PubMed Central

    Stone, John E.; Hallock, Michael J.; Phillips, James C.; Peterson, Joseph R.; Luthey-Schulten, Zaida; Schulten, Klaus

    2016-01-01

    Many of the continuing scientific advances achieved through computational biology are predicated on the availability of ongoing increases in computational power required for detailed simulation and analysis of cellular processes on biologically-relevant timescales. A critical challenge facing the development of future exascale supercomputer systems is the development of new computing hardware and associated scientific applications that dramatically improve upon the energy efficiency of existing solutions, while providing increased simulation, analysis, and visualization performance. Mobile computing platforms have recently become powerful enough to support interactive molecular visualization tasks that were previously only possible on laptops and workstations, creating future opportunities for their convenient use for meetings, remote collaboration, and as head mounted displays for immersive stereoscopic viewing. We describe early experiences adapting several biomolecular simulation and analysis applications for emerging heterogeneous computing platforms that combine power-efficient system-on-chip multi-core CPUs with high-performance massively parallel GPUs. We present low-cost power monitoring instrumentation that provides sufficient temporal resolution to evaluate the power consumption of individual CPU algorithms and GPU kernels. We compare the performance and energy efficiency of scientific applications running on emerging platforms with results obtained on traditional platforms, identify hardware and algorithmic performance bottlenecks that affect the usability of these platforms, and describe avenues for improving both the hardware and applications in pursuit of the needs of molecular modeling tasks on mobile devices and future exascale computers. PMID:27516922

  19. Agent-Based Spatiotemporal Simulation of Biomolecular Systems within the Open Source MASON Framework

    PubMed Central

    Pérez-Rodríguez, Gael; Pérez-Pérez, Martín; Glez-Peña, Daniel; Azevedo, Nuno F.; Lourenço, Anália

    2015-01-01

    Agent-based modelling is being used to represent biological systems with increasing frequency and success. This paper presents the implementation of a new tool for biomolecular reaction modelling in the open source Multiagent Simulator of Neighborhoods framework. The rationale behind this new tool is the necessity to describe interactions at the molecular level to be able to grasp emergent and meaningful biological behaviour. We are particularly interested in characterising and quantifying the various effects that facilitate biocatalysis. Enzymes may display high specificity for their substrates and this information is crucial to the engineering and optimisation of bioprocesses. Simulation results demonstrate that molecule distributions, reaction rate parameters, and structural parameters can be adjusted separately in the simulation allowing a comprehensive study of individual effects in the context of realistic cell environments. While higher percentage of collisions with occurrence of reaction increases the affinity of the enzyme to the substrate, a faster reaction (i.e., turnover number) leads to a smaller number of time steps. Slower diffusion rates and molecular crowding (physical hurdles) decrease the collision rate of reactants, hence reducing the reaction rate, as expected. Also, the random distribution of molecules affects the results significantly. PMID:25874228

  20. Mixing MARTINI: electrostatic coupling in hybrid atomistic-coarse-grained biomolecular simulations.

    PubMed

    Wassenaar, Tsjerk A; Ingólfsson, Helgi I; Priess, Marten; Marrink, Siewert J; Schäfer, Lars V

    2013-04-01

    biomolecular simulations. PMID:23406326

  1. A coarse-grained model for the simulations of biomolecular interactions in cellular environments

    SciTech Connect

    Xie, Zhong-Ru; Chen, Jiawen; Wu, Yinghao

    2014-02-07

    The interactions of bio-molecules constitute the key steps of cellular functions. However, in vivo binding properties differ significantly from their in vitro measurements due to the heterogeneity of cellular environments. Here we introduce a coarse-grained model based on rigid-body representation to study how factors such as cellular crowding and membrane confinement affect molecular binding. The macroscopic parameters such as the equilibrium constant and the kinetic rate constant are calibrated by adjusting the microscopic coefficients used in the numerical simulations. By changing these model parameters that are experimentally approachable, we are able to study the kinetic and thermodynamic properties of molecular binding, as well as the effects caused by specific cellular environments. We investigate the volumetric effects of crowded intracellular space on bio-molecular diffusion and diffusion-limited reactions. Furthermore, the binding constants of membrane proteins are currently difficult to measure. We provide quantitative estimations about how the binding of membrane proteins deviates from soluble proteins under different degrees of membrane confinements. The simulation results provide biological insights to the functions of membrane receptors on cell surfaces. Overall, our studies establish a connection between the details of molecular interactions and the heterogeneity of cellular environments.

  2. Masking Resonance Artifacts in Force-Splitting Methods for Biomolecular Simulations by Extrapolative Langevin Dynamics

    NASA Astrophysics Data System (ADS)

    Sandu, Adrian; Schlick, Tamar

    1999-05-01

    Numerical resonance artifacts have become recognized recently as a limiting factor to increasing the timestep in multiple-timestep (MTS) biomolecular dynamics simulations. At certain timesteps correlated to internal motions (e.g., 5 fs, around half the period of the fastest bond stretch, Tmin), visible inaccuracies or instabilities can occur. Impulse-MTS schemes are vulnerable to these resonance errors since large energy pulses are introduced to the governing dynamics equations when the slow forces are evaluated. We recently showed that such resonance artifacts can be masked significantly by applying extrapolative splitting to stochastic dynamics. Theoretical and numerical analyses of force-splitting integrators based on the Verlet discretization are reported here for linear models to explain these observations and to suggest how to construct effective integrators for biomolecular dynamics that balance stability with accuracy. Analyses for Newtonian dynamics demonstrate the severe resonance patterns of the Impulse splitting, with this severity worsening with the outer timestep, Δ t; Constant Extrapolation is generally unstable, but the disturbances do not grow with Δ t. Thus, the stochastic extrapolative combination can counteract generic instabilities and largely alleviate resonances with a sufficiently strong Langevin heat-bath coupling (γ), estimates for which are derived here based on the fastest and slowest motion periods. These resonance results generally hold for nonlinear test systems: a water tetramer and solvated protein. Proposed related approaches such as Extrapolation/Correction and Midpoint Extrapolation work better than Constant Extrapolation only for timesteps less than Tmin/2. An effective extrapolative stochastic approach for biomolecules that balances long-timestep stability with good accuracy for the fast subsystem is then applied to a biomolecule using a three-class partitioning: the medium forces are treated by Midpoint Extrapolationvia

  3. Poisson-Nernst-Planck equations for simulating biomolecular diffusion-reaction processes I: Finite element solutions

    SciTech Connect

    Lu Benzhuo; Andrew McCammon, J.; Zhou, Y.C.

    2010-09-20

    In this paper we developed accurate finite element methods for solving 3-D Poisson-Nernst-Planck (PNP) equations with singular permanent charges for simulating electrodiffusion in solvated biomolecular systems. The electrostatic Poisson equation was defined in the biomolecules and in the solvent, while the Nernst-Planck equation was defined only in the solvent. We applied a stable regularization scheme to remove the singular component of the electrostatic potential induced by the permanent charges inside biomolecules, and formulated regular, well-posed PNP equations. An inexact-Newton method was used to solve the coupled nonlinear elliptic equations for the steady problems; while an Adams-Bashforth-Crank-Nicolson method was devised for time integration for the unsteady electrodiffusion. We numerically investigated the conditioning of the stiffness matrices for the finite element approximations of the two formulations of the Nernst-Planck equation, and theoretically proved that the transformed formulation is always associated with an ill-conditioned stiffness matrix. We also studied the electroneutrality of the solution and its relation with the boundary conditions on the molecular surface, and concluded that a large net charge concentration is always present near the molecular surface due to the presence of multiple species of charged particles in the solution. The numerical methods are shown to be accurate and stable by various test problems, and are applicable to real large-scale biophysical electrodiffusion problems.

  4. Macromolecular character of amber

    SciTech Connect

    Wert, C.A.; Weller, M.; Schlee, D.; Ledbetter, H.

    1989-03-15

    Measurements are reported of anelastic and dielectric loss of various ambers and copals. They show spectra typical of synthetic polymers. This similarity permits description of the macromolecular character of amber which was not possible from previous studies of chemical composition. Measurements on amber of several origins and geological ages show generally similar character, but also differences in detail. These may be caused by differences in chemistry of the original resin and the geological age and history of the amber, reflecting differences in degree of polymerization. Also reported are elastic constants measured at high frequency.

  5. A synergic simulation-optimization approach for analyzing biomolecular dynamics in living organisms.

    PubMed

    Sadegh Zadeh, Kouroush

    2011-01-01

    A synergic duo simulation-optimization approach was developed and implemented to study protein-substrate dynamics and binding kinetics in living organisms. The forward problem is a system of several coupled nonlinear partial differential equations which, with a given set of kinetics and diffusion parameters, can provide not only the commonly used bleached area-averaged time series in fluorescence microscopy experiments but more informative full biomolecular/drug space-time series and can be successfully used to study dynamics of both Dirac and Gaussian fluorescence-labeled biomacromolecules in vivo. The incomplete Cholesky preconditioner was coupled with the finite difference discretization scheme and an adaptive time-stepping strategy to solve the forward problem. The proposed approach was validated with analytical as well as reference solutions and used to simulate dynamics of GFP-tagged glucocorticoid receptor (GFP-GR) in mouse cancer cell during a fluorescence recovery after photobleaching experiment. Model analysis indicates that the commonly practiced bleach spot-averaged time series is not an efficient approach to extract physiological information from the fluorescence microscopy protocols. It was recommended that experimental biophysicists should use full space-time series, resulting from experimental protocols, to study dynamics of biomacromolecules and drugs in living organisms. It was also concluded that in parameterization of biological mass transfer processes, setting the norm of the gradient of the penalty function at the solution to zero is not an efficient stopping rule to end the inverse algorithm. Theoreticians should use multi-criteria stopping rules to quantify model parameters by optimization. PMID:21106190

  6. CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field

    SciTech Connect

    Lee, Jumin; Cheng, Xi; Swails, Jason M.; Yeom, Min Sun; Eastman, Peter K.; Lemkul, Justin A.; Wei, Shuai; Buckner, Joshua; Jeong, Jong Cheol; Qi, Yifei; Jo, Sunhwan; Pande, Vijay S.; Case, David A.; Brooks, Charles L.; MacKerell, Alexander D.; Klauda, Jeffery B.; Im, Wonpil

    2015-11-12

    Here we report that proper treatment of nonbonded interactions is essential for the accuracy of molecular dynamics (MD) simulations, especially in studies of lipid bilayers. The use of the CHARMM36 force field (C36 FF) in different MD simulation programs can result in disagreements with published simulations performed with CHARMM due to differences in the protocols used to treat the long-range and 1-4 nonbonded interactions. In this study, we systematically test the use of the C36 lipid FF in NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM. A wide range of Lennard-Jones (LJ) cutoff schemes and integrator algorithms were tested to find the optimal simulation protocol to best match bilayer properties of six lipids with varying acyl chain saturation and head groups. MD simulations of a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer were used to obtain the optimal protocol for each program. MD simulations with all programs were found to reasonably match the DPPC bilayer properties (surface area per lipid, chain order parameters, and area compressibility modulus) obtained using the standard protocol used in CHARMM as well as from experiments. The optimal simulation protocol was then applied to the other five lipid simulations and resulted in excellent agreement between results from most simulation programs as well as with experimental data. AMBER compared least favorably with the expected membrane properties, which appears to be due to its use of the hard-truncation in the LJ potential versus a force-based switching function used to smooth the LJ potential as it approaches the cutoff distance. The optimal simulation protocol for each program has been implemented in CHARMM-GUI. This protocol is expected to be applicable to the remainder of the additive C36 FF including the proteins, nucleic acids, carbohydrates, and small molecules.

  7. CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field

    PubMed Central

    2015-01-01

    Proper treatment of nonbonded interactions is essential for the accuracy of molecular dynamics (MD) simulations, especially in studies of lipid bilayers. The use of the CHARMM36 force field (C36 FF) in different MD simulation programs can result in disagreements with published simulations performed with CHARMM due to differences in the protocols used to treat the long-range and 1-4 nonbonded interactions. In this study, we systematically test the use of the C36 lipid FF in NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM. A wide range of Lennard-Jones (LJ) cutoff schemes and integrator algorithms were tested to find the optimal simulation protocol to best match bilayer properties of six lipids with varying acyl chain saturation and head groups. MD simulations of a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer were used to obtain the optimal protocol for each program. MD simulations with all programs were found to reasonably match the DPPC bilayer properties (surface area per lipid, chain order parameters, and area compressibility modulus) obtained using the standard protocol used in CHARMM as well as from experiments. The optimal simulation protocol was then applied to the other five lipid simulations and resulted in excellent agreement between results from most simulation programs as well as with experimental data. AMBER compared least favorably with the expected membrane properties, which appears to be due to its use of the hard-truncation in the LJ potential versus a force-based switching function used to smooth the LJ potential as it approaches the cutoff distance. The optimal simulation protocol for each program has been implemented in CHARMM-GUI. This protocol is expected to be applicable to the remainder of the additive C36 FF including the proteins, nucleic acids, carbohydrates, and small molecules. PMID:26631602

  8. CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field

    DOE PAGESBeta

    Lee, Jumin; Cheng, Xi; Swails, Jason M.; Yeom, Min Sun; Eastman, Peter K.; Lemkul, Justin A.; Wei, Shuai; Buckner, Joshua; Jeong, Jong Cheol; Qi, Yifei; et al

    2015-11-12

    Here we report that proper treatment of nonbonded interactions is essential for the accuracy of molecular dynamics (MD) simulations, especially in studies of lipid bilayers. The use of the CHARMM36 force field (C36 FF) in different MD simulation programs can result in disagreements with published simulations performed with CHARMM due to differences in the protocols used to treat the long-range and 1-4 nonbonded interactions. In this study, we systematically test the use of the C36 lipid FF in NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM. A wide range of Lennard-Jones (LJ) cutoff schemes and integrator algorithms were tested to find themore » optimal simulation protocol to best match bilayer properties of six lipids with varying acyl chain saturation and head groups. MD simulations of a 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) bilayer were used to obtain the optimal protocol for each program. MD simulations with all programs were found to reasonably match the DPPC bilayer properties (surface area per lipid, chain order parameters, and area compressibility modulus) obtained using the standard protocol used in CHARMM as well as from experiments. The optimal simulation protocol was then applied to the other five lipid simulations and resulted in excellent agreement between results from most simulation programs as well as with experimental data. AMBER compared least favorably with the expected membrane properties, which appears to be due to its use of the hard-truncation in the LJ potential versus a force-based switching function used to smooth the LJ potential as it approaches the cutoff distance. The optimal simulation protocol for each program has been implemented in CHARMM-GUI. This protocol is expected to be applicable to the remainder of the additive C36 FF including the proteins, nucleic acids, carbohydrates, and small molecules.« less

  9. Optimal Use of Data in Parallel Tempering Simulations for the Construction of Discrete-State Markov Models of Biomolecular Dynamics

    SciTech Connect

    Prinz, Jan-Hendrik; Chondera, John D; Pande, Vijay S; Swope, William C; Smith, Jeremy C; Noe, F

    2011-01-01

    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.

  10. Implementation of the SCC-DFTB Method for Hybrid QM/MM Simulations within the Amber Molecular Dynamics Package

    PubMed Central

    de M. Seabra, Gustavo; Walker, Ross C.; Elstner, Marcus; Case, David A.; Roitberg, Adrian E.

    2011-01-01

    Self-Consistent Charge Density Functional Tight Binding (SCC-DFTB) is a semi-empirical method based on Density Functional Theory, and has in many cases been shown to provide relative energies and geometries comparable in accuracy to full DFT or ab-initio MP2 calculations using large basis sets. This article shows an implementation of the SCC-DFTB method as part of the new QM/MM support in the AMBER 9 molecular dynamics program suite. Details of the implementation and examples of applications are shown. PMID:17521173

  11. Assessing the Current State of Amber Force Field Modifications for DNA.

    PubMed

    Galindo-Murillo, Rodrigo; Robertson, James C; Zgarbová, Marie; Šponer, Jiří; Otyepka, Michal; Jurečka, Petr; Cheatham, Thomas E

    2016-08-01

    The utility of molecular dynamics (MD) simulations to model biomolecular structure, dynamics, and interactions has witnessed enormous advances in recent years due to the availability of optimized MD software and access to significant computational power, including GPU multicore computing engines and other specialized hardware. This has led researchers to routinely extend conformational sampling times to the microsecond level and beyond. The extended sampling time has allowed the community not only to converge conformational ensembles through complete sampling but also to discover deficiencies and overcome problems with the force fields. Accuracy of the force fields is a key component, along with sampling, toward being able to generate accurate and stable structures of biopolymers. The Amber force field for nucleic acids has been used extensively since the 1990s, and multiple artifacts have been discovered, corrected, and reassessed by different research groups. We present a direct comparison of two of the most recent and state-of-the-art Amber force field modifications, bsc1 and OL15, that focus on accurate modeling of double-stranded DNA. After extensive MD simulations with five test cases and two different water models, we conclude that both modifications are a remarkable improvement over the previous bsc0 force field. Both force field modifications show better agreement when compared to experimental structures. To ensure convergence, the Drew-Dickerson dodecamer (DDD) system was simulated using 100 independent MD simulations, each extended to at least 10 μs, and the independent MD simulations were concatenated into a single 1 ms long trajectory for each combination of force field and water model. This is significantly beyond the time scale needed to converge the conformational ensemble of the internal portions of a DNA helix absent internal base pair opening. Considering all of the simulations discussed in the current work, the MD simulations performed to

  12. Assessing the Current State of Amber Force Field Modifications for DNA

    PubMed Central

    2016-01-01

    The utility of molecular dynamics (MD) simulations to model biomolecular structure, dynamics, and interactions has witnessed enormous advances in recent years due to the availability of optimized MD software and access to significant computational power, including GPU multicore computing engines and other specialized hardware. This has led researchers to routinely extend conformational sampling times to the microsecond level and beyond. The extended sampling time has allowed the community not only to converge conformational ensembles through complete sampling but also to discover deficiencies and overcome problems with the force fields. Accuracy of the force fields is a key component, along with sampling, toward being able to generate accurate and stable structures of biopolymers. The Amber force field for nucleic acids has been used extensively since the 1990s, and multiple artifacts have been discovered, corrected, and reassessed by different research groups. We present a direct comparison of two of the most recent and state-of-the-art Amber force field modifications, bsc1 and OL15, that focus on accurate modeling of double-stranded DNA. After extensive MD simulations with five test cases and two different water models, we conclude that both modifications are a remarkable improvement over the previous bsc0 force field. Both force field modifications show better agreement when compared to experimental structures. To ensure convergence, the Drew–Dickerson dodecamer (DDD) system was simulated using 100 independent MD simulations, each extended to at least 10 μs, and the independent MD simulations were concatenated into a single 1 ms long trajectory for each combination of force field and water model. This is significantly beyond the time scale needed to converge the conformational ensemble of the internal portions of a DNA helix absent internal base pair opening. Considering all of the simulations discussed in the current work, the MD simulations performed to

  13. Comparison of structural, thermodynamic, kinetic and mass transport properties of Mg2+ ion models commonly used in biomolecular simulations

    PubMed Central

    Panteva, Maria T.; GiambaȈsu, George M.; York, Darrin M.

    2015-01-01

    The prevalence of Mg2+ ions in biology and their essential role in nucleic acid structure and function has motivated the development of various Mg2+ ion models for use in molecular simulations. Currently the most widely used models in biomolecular simulations represent a non-bonded metal ion as an ion-centered point charge surrounded by a non-electrostatic 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 Mg2+ 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 non-bonded single-site Mg2+ 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 non-electrostatic non-bonded 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 Mg2+ 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. PMID:25736394

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

    PubMed

    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. PMID:25736394

  15. Poisson-Nernst-Planck Equations for Simulating Biomolecular Diffusion-Reaction Processes I: Finite Element Solutions

    PubMed Central

    Lu, Benzhuo; Holst, Michael J.; McCammon, J. Andrew; Zhou, Y. C.

    2010-01-01

    In this paper we developed accurate finite element methods for solving 3-D Poisson-Nernst-Planck (PNP) equations with singular permanent charges for electrodiffusion in solvated biomolecular systems. The electrostatic Poisson equation was defined in the biomolecules and in the solvent, while the Nernst-Planck equation was defined only in the solvent. We applied a stable regularization scheme to remove the singular component of the electrostatic potential induced by the permanent charges inside biomolecules, and formulated regular, well-posed PNP equations. An inexact-Newton method was used to solve the coupled nonlinear elliptic equations for the steady problems; while an Adams-Bashforth-Crank-Nicolson method was devised for time integration for the unsteady electrodiffusion. We numerically investigated the conditioning of the stiffness matrices for the finite element approximations of the two formulations of the Nernst-Planck equation, and theoretically proved that the transformed formulation is always associated with an ill-conditioned stiffness matrix. We also studied the electroneutrality of the solution and its relation with the boundary conditions on the molecular surface, and concluded that a large net charge concentration is always present near the molecular surface due to the presence of multiple species of charged particles in the solution. The numerical methods are shown to be accurate and stable by various test problems, and are applicable to real large-scale biophysical electrodiffusion problems. PMID:21709855

  16. Lipid14: The Amber Lipid Force Field.

    PubMed

    Dickson, Callum J; Madej, Benjamin D; Skjevik, Age A; Betz, Robin M; Teigen, Knut; Gould, Ian R; Walker, Ross C

    2014-02-11

    The AMBER lipid force field has been updated to create Lipid14, allowing tensionless simulation of a number of lipid types with the AMBER MD package. The modular nature of this force field allows numerous combinations of head and tail groups to create different lipid types, enabling the easy insertion of new lipid species. The Lennard-Jones and torsion parameters of both the head and tail groups have been revised and updated partial charges calculated. The force field has been validated by simulating bilayers of six different lipid types for a total of 0.5 μs each without applying a surface tension; with favorable comparison to experiment for properties such as area per lipid, volume per lipid, bilayer thickness, NMR order parameters, scattering data, and lipid lateral diffusion. As the derivation of this force field is consistent with the AMBER development philosophy, Lipid14 is compatible with the AMBER protein, nucleic acid, carbohydrate, and small molecule force fields. PMID:24803855

  17. Extension of the CHARMM General Force Field to sulfonyl-containing compounds and its utility in biomolecular simulations.

    PubMed

    Yu, Wenbo; He, Xibing; Vanommeslaeghe, Kenno; MacKerell, Alexander D

    2012-12-01

    Presented is an extension of the CHARMM General Force Field (CGenFF) to enable the modeling of sulfonyl-containing compounds. Model compounds containing chemical moieties such as sulfone, sulfonamide, sulfonate, and sulfamate were used as the basis for the parameter optimization. Targeting high-level quantum mechanical and experimental crystal data, the new parameters were optimized in a hierarchical fashion designed to maintain compatibility with the remainder of the CHARMM additive force field. The optimized parameters satisfactorily reproduced equilibrium geometries, vibrational frequencies, interactions with water, gas phase dipole moments, and dihedral potential energy scans. Validation involved both crystalline and liquid phase calculations showing the newly developed parameters to satisfactorily reproduce experimental unit cell geometries, crystal intramolecular geometries, and pure solvent densities. The force field was subsequently applied to study conformational preference of a sulfonamide based peptide system. Good agreement with experimental IR/NMR data further validated the newly developed CGenFF parameters as a tool to investigate the dynamic behavior of sulfonyl groups in a biological environment. CGenFF now covers sulfonyl group containing moieties allowing for modeling and simulation of sulfonyl-containing compounds in the context of biomolecular systems including compounds of medicinal interest. PMID:22821581

  18. AMBER User's Manual

    SciTech Connect

    Vay, J.L.; Fawley, W.

    2000-11-08

    AMBER is a Particle-In-Cell (PIC) code which models the evolution of a representative slice of a relativistic electron beam in a linear accelerator. The beam is modeled as a steady flow and therefore no electromagnetic waves: all the fields (external and self-fields) are electrostatic and magnetostatic fields (for a complete description, see chapter 5). The possible elements describing the accelerator lattice are solenoids, accelerating gaps, pipes and apertures. Several kinds of beam distribution can be loaded: KV, gaussian, semi-gaussian, etc. Alternatively, the user can reconstruct (or load) a distribution from the output of another codefile, for example, an interface generating the beam distribution from output produced from EGUN or LSP codes is available as an option. This documentation first describes in detail the input files needed to run AMBER and the procedure to start the executable. The possible data files and graphical output are explained in the two following chapters. The last chapter describes the physics model and numerical techniques used. An example of input files and the result obtained with these inputs are also given in the Appendix.

  19. PIP(2)-binding site in Kir channels: definition by multiscale biomolecular simulations.

    PubMed

    Stansfeld, Phillip J; Hopkinson, Richard; Ashcroft, Frances M; Sansom, Mark S P

    2009-11-24

    Phosphatidylinositol bisphosphate (PIP(2)) is an activator of mammalian inwardly rectifying potassium (Kir) channels. Multiscale simulations, via a sequential combination of coarse-grained and atomistic molecular dynamics, enabled exploration of the interactions of PIP(2) molecules within the inner leaflet of a lipid bilayer membrane with possible binding sites on Kir channels. Three Kir channel structures were investigated: X-ray structures of KirBac1.1 and of a Kir3.1-KirBac1.3 chimera and a homology model of Kir6.2. Coarse-grained simulations of the Kir channels in PIP(2)-containing lipid bilayers identified the PIP(2)-binding site on each channel. These models of the PIP(2)-channel complexes were refined by conversion to an atomistic representation followed by molecular dynamics simulation in a lipid bilayer. All three channels were revealed to contain a conserved binding site at the N-terminal end of the slide (M0) helix, at the interface between adjacent subunits of the channel. This binding site agrees with mutagenesis data and is in the proximity of the site occupied by a detergent molecule in the Kir chimera channel crystal. Polar contacts in the coarse-grained simulations corresponded to long-lived electrostatic and H-bonding interactions between the channel and PIP(2) in the atomistic simulations, enabling identification of key side chains. PMID:19839652

  20. REACH coarse-grained biomolecular simulation: transferability between different protein structural classes.

    PubMed

    Moritsugu, Kei; Smith, Jeremy C

    2008-08-01

    Coarse graining of protein interactions provides a means of simulating large biological systems. The REACH (Realistic Extension Algorithm via Covariance Hessian) coarse-graining method, in which the force constants of a residue-scale elastic network model are calculated from the variance-covariance matrix obtained from atomistic molecular dynamics (MD) simulation, involves direct mapping between scales without the need for iterative optimization. Here, the transferability of the REACH force field is examined between protein molecules of different structural classes. As test cases, myoglobin (all alpha), plastocyanin (all beta), and dihydrofolate reductase (alpha/beta) are taken. The force constants derived are found to be closely similar in all three proteins. An MD version of REACH is presented, and low-temperature coarse-grained (CG) REACH MD simulations of the three proteins are compared with atomistic MD results. The mean-square fluctuations of the atomistic MD are well reproduced by the CGMD. Model functions for the CG interactions, derived by averaging over the three proteins, are also shown to produce fluctuations in good agreement with the atomistic MD. The results indicate that, similarly to the use of atomistic force fields, it is now possible to use a single, generic REACH force field for all protein studies, without having first to derive parameters from atomistic MD simulation for each individual system studied. The REACH method is thus likely to be a reliable way of determining spatiotemporal motion of a variety of proteins without the need for expensive computation of long atomistic MD simulations. PMID:18469078

  1. Mapping to Irregular Torus Topologies and Other Techniques for Petascale Biomolecular Simulation

    PubMed Central

    Phillips, James C.; Sun, Yanhua; Jain, Nikhil; Bohm, Eric J.; Kalé, Laxmikant V.

    2014-01-01

    Currently deployed petascale supercomputers typically use toroidal network topologies in three or more dimensions. While these networks perform well for topology-agnostic codes on a few thousand nodes, leadership machines with 20,000 nodes require topology awareness to avoid network contention for communication-intensive codes. Topology adaptation is complicated by irregular node allocation shapes and holes due to dedicated input/output nodes or hardware failure. In the context of the popular molecular dynamics program NAMD, we present methods for mapping a periodic 3-D grid of fixed-size spatial decomposition domains to 3-D Cray Gemini and 5-D IBM Blue Gene/Q toroidal networks to enable hundred-million atom full machine simulations, and to similarly partition node allocations into compact domains for smaller simulations using multiple-copy algorithms. Additional enabling techniques are discussed and performance is reported for NCSA Blue Waters, ORNL Titan, ANL Mira, TACC Stampede, and NERSC Edison. PMID:25594075

  2. On the structural convergence of biomolecular simulations by determination of the effective sample size

    PubMed Central

    Lyman, Edward; Zuckerman, Daniel M.

    2008-01-01

    Although atomistic simulations of proteins and other biological systems are approaching microsecond timescales, the quality of simulation trajectories has remained difficult to assess. Such assessment is critical not only for establishing the relevance of any individual simulation, but also in the extremely active field of developing computational methods. Here we map the trajectory assessment problem onto a simple statistical calculation of the “effective sample size” - i.e., the number of statistically independent configurations. The mapping is achieved by asking the question, “How much time must elapse between snapshots included in a sample for that sample to exhibit the statistical properties expected for independent and identically distributed configurations?” Our method is more general than standard autocorrelation methods, in that it directly probes the configuration space distribution, without requiring a priori definition of configurational substates, and without any fitting parameters. We show that the method is equally and directly applicable to toy models, peptides, and a 72-residue protein model. Variants of our approach can readily be applied to a wide range of physical and chemical systems. PMID:17935314

  3. Multi-resolution simulation of biomolecular systems: a review of methodological issues.

    PubMed

    Meier, Katharina; Choutko, Alexandra; Dolenc, Jozica; Eichenberger, Andreas P; Riniker, Sereina; van Gunsteren, Wilfred F

    2013-03-01

    Theoretical-computational modeling with an eye to explaining experimental observations in regard to a particular chemical phenomenon or process requires choices concerning essential degrees of freedom and types of interactions and the generation of a Boltzmann ensemble or trajectories of configurations. Depending on the degrees of freedom that are essential to the process of interest, for example, electronic or nuclear versus atomic, molecular or supra-molecular, quantum- or classical-mechanical equations of motion are to be used. In multi-resolution simulation, various levels of resolution, for example, electronic, atomic, supra-atomic or supra-molecular, are combined in one model. This allows an enhancement of the computational efficiency, while maintaining sufficient detail with respect to particular degrees of freedom. The basic challenges and choices with respect to multi-resolution modeling are reviewed and as an illustration the differential catalytic properties of two enzymes with similar folds but different substrates with respect to these substrates are explored using multi-resolution simulation at the electronic, atomic and supra-molecular levels of resolution. PMID:23417997

  4. Identifying localized changes in large systems: Change-point detection for biomolecular simulations

    PubMed Central

    Fan, Zhou; Dror, Ron O.; Mildorf, Thomas J.; Piana, Stefano; Shaw, David E.

    2015-01-01

    Research on change-point detection, the classical problem of detecting abrupt changes in sequential data, has focused predominantly on datasets with a single observable. A growing number of time series datasets, however, involve many observables, often with the property that a given change typically affects only a few of the observables. We introduce a general statistical method that, given many noisy observables, detects points in time at which various subsets of the observables exhibit simultaneous changes in data distribution and explicitly identifies those subsets. Our work is motivated by the problem of identifying the nature and timing of biologically interesting conformational changes that occur during atomic-level simulations of biomolecules such as proteins. This problem has proved challenging both because each such conformational change might involve only a small region of the molecule and because these changes are often subtle relative to the ever-present background of faster structural fluctuations. We show that our method is effective in detecting biologically interesting conformational changes in molecular dynamics simulations of both folded and unfolded proteins, even in cases where these changes are difficult to detect using alternative techniques. This method may also facilitate the detection of change points in other types of sequential data involving large numbers of observables—a problem likely to become increasingly important as such data continue to proliferate in a variety of application domains. PMID:26025225

  5. Best bang for your buck: GPU nodes for GROMACS biomolecular simulations.

    PubMed

    Kutzner, Carsten; Páll, Szilárd; Fechner, Martin; Esztermann, Ansgar; de Groot, Bert L; Grubmüller, Helmut

    2015-10-01

    The molecular dynamics simulation package GROMACS runs efficiently on a wide variety of hardware from commodity workstations to high performance computing clusters. Hardware features are well-exploited with a combination of single instruction multiple data, multithreading, and message passing interface (MPI)-based single program multiple data/multiple program multiple data parallelism while graphics processing units (GPUs) can be used as accelerators to compute interactions off-loaded from the CPU. Here, we evaluate which hardware produces trajectories with GROMACS 4.6 or 5.0 in the most economical way. We have assembled and benchmarked compute nodes with various CPU/GPU combinations to identify optimal compositions in terms of raw trajectory production rate, performance-to-price ratio, energy efficiency, and several other criteria. Although hardware prices are naturally subject to trends and fluctuations, general tendencies are clearly visible. Adding any type of GPU significantly boosts a node's simulation performance. For inexpensive consumer-class GPUs this improvement equally reflects in the performance-to-price ratio. Although memory issues in consumer-class GPUs could pass unnoticed as these cards do not support error checking and correction memory, unreliable GPUs can be sorted out with memory checking tools. Apart from the obvious determinants for cost-efficiency like hardware expenses and raw performance, the energy consumption of a node is a major cost factor. Over the typical hardware lifetime until replacement of a few years, the costs for electrical power and cooling can become larger than the costs of the hardware itself. Taking that into account, nodes with a well-balanced ratio of CPU and consumer-class GPU resources produce the maximum amount of GROMACS trajectory over their lifetime. PMID:26238484

  6. Reproducing kernel potential energy surfaces in biomolecular simulations: Nitric oxide binding to myoglobin

    SciTech Connect

    Soloviov, Maksym; Meuwly, Markus

    2015-09-14

    Multidimensional potential energy surfaces based on reproducing kernel-interpolation are employed to explore the energetics and dynamics of free and bound nitric oxide in myoglobin (Mb). Combining a force field description for the majority of degrees of freedom and the higher-accuracy representation for the NO ligand and the Fe out-of-plane motion allows for a simulation approach akin to a mixed quantum mechanics/molecular mechanics treatment. However, the kernel-representation can be evaluated at conventional force-field speed. With the explicit inclusion of the Fe-out-of-plane (Fe-oop) coordinate, the dynamics and structural equilibrium after photodissociation of the ligand are correctly described compared to experiment. Experimentally, the Fe-oop coordinate plays an important role for the ligand dynamics. This is also found here where the isomerization dynamics between the Fe–ON and Fe–NO state is significantly affected whether or not this co-ordinate is explicitly included. Although the Fe–ON conformation is metastable when considering only the bound {sup 2}A state, it may disappear once the {sup 4}A state is included. This explains the absence of the Fe–ON state in previous experimental investigations of MbNO.

  7. Dynamics of biomolecular processes

    NASA Astrophysics Data System (ADS)

    Behringer, Hans; Eichhorn, Ralf; Wallin, Stefan

    2013-05-01

    The last few years have seen enormous progress in the availability of computational resources, so that the size and complexity of physical systems that can be investigated numerically has increased substantially. The physical mechanisms behind the processes creating life, such as those in a living cell, are of foremost interest in biophysical research. A main challenge here is that complexity not only emerges from interactions of many macro-molecular compounds, but is already evident at the level of a single molecule. An exciting recent development in this context is, therefore, that detailed atomistic level characterization of large-scale dynamics of individual bio-macromolecules, such as proteins and DNA, is starting to become feasible in some cases. This has contributed to a better understanding of the molecular mechanisms of, e.g. protein folding and aggregation, as well as DNA dynamics. Nevertheless, simulations of the dynamical behaviour of complex multicomponent cellular processes at an all-atom level will remain beyond reach for the foreseeable future, and may not even be desirable. Ultimate understanding of many biological processes will require the development of methods targeting different time and length scales and, importantly, ways to bridge these in multiscale approaches. At the scientific programme Dynamics of biomolecular processes: from atomistic representations to coarse-grained models held between 27 February and 23 March 2012, and hosted by the Nordic Institute for Theoretical Physics, new modelling approaches and results for particular biological systems were presented and discussed. The programme was attended by around 30 scientists from the Nordic countries and elsewhere. It also included a PhD and postdoc 'winter school', where basic theoretical concepts and techniques of biomolecular modelling and simulations were presented. One to two decades ago, the biomolecular modelling field was dominated by two widely different and largely

  8. Where Does Amber Come from?

    ERIC Educational Resources Information Center

    Booth, Bibi

    2005-01-01

    Amber is the fossilized resin of now-extinct trees, primarily ancient conifers but also some flowering tropical trees. An aromatic, soft, sticky substance, resin in extinct trees probably served the same purposes as resin in modern trees: to protect the plant by sealing cuts and by excluding bacteria, fungi, and insects.

  9. Event Detection and Sub-state Discovery from Bio-molecular Simulations Using Higher-Order Statistics: Application To Enzyme Adenylate Kinase

    PubMed Central

    Ramanathan, Arvind; Savol, Andrej J.; Agarwal, Pratul K.; Chennubhotla, Chakra S.

    2012-01-01

    Biomolecular simulations at milli-second and longer timescales can provide vital insights into functional mechanisms. Since post-simulation analyses of such large trajectory data-sets can be a limiting factor in obtaining biological insights, there is an emerging need to identify key dynamical events and relating these events to the biological function online, that is, as simulations are progressing. Recently, we have introduced a novel computational technique, quasi-anharmonic analysis (QAA) (PLoS One 6(1): e15827), for partitioning the conformational landscape into a hierarchy of functionally relevant sub-states. The unique capabilities of QAA are enabled by exploiting anharmonicity in the form of fourth-order statistics for characterizing atomic fluctuations. In this paper, we extend QAA for analyzing long time-scale simulations online. In particular, we present HOST4MD - a higher-order statistical toolbox for molecular dynamics simulations, which (1) identifies key dynamical events as simulations are in progress, (2) explores potential sub-states and (3) identifies conformational transitions that enable the protein to access those sub-states. We demonstrate HOST4MD on micro-second time-scale simulations of the enzyme adenylate kinase in its apo state. HOST4MD identifies several conformational events in these simulations, revealing how the intrinsic coupling between the three sub-domains (LID, CORE and NMP) changes during the simulations. Further, it also identifies an inherent asymmetry in the opening/closing of the two binding sites. We anticipate HOST4MD will provide a powerful and extensible framework for detecting biophysically relevant conformational coordinates from long time-scale simulations. PMID:22733562

  10. Biomolecular Science (Fact Sheet)

    SciTech Connect

    Not Available

    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.

  11. Comparing amber fossil assemblages across the Cenozoic

    PubMed Central

    Penney, David; Langan, A. Mark

    2006-01-01

    To justify faunistic comparisons of ambers that differ botanically, geographically and by age, we need to determine that resins sampled uniformly. Our pluralistic approach, analysing size distributions of 671 fossilized spider species from different behavioural guilds, demonstrates that ecological information about the communities of two well-studied ambers is retained. Several lines of evidence show that greater structural complexity of Baltic compared to Dominican amber trees explains the presence of larger web-spinners. No size differences occur in active hunters. Consequently, we demonstrate for the first time that resins were trapping organisms uniformly and that comparisons of amber palaeoecosystem structure across deep time are possible. PMID:17148379

  12. Dynamics of biomolecular fibers

    NASA Astrophysics Data System (ADS)

    Plewa, Joseph Steven

    We describe theoretical and experimental investigations of biomolecular dynamics. First we demonstrate a lattice Monte Carlo simulation which conserves a topological linking number by forbidding moves through cis conformations. Unlike previous models that conserve linking number, our simulated ring chains have flexibility and the scaling properties of a lattice self-avoiding walk. A linking number of order 0.2 per bond leads to an eight-percent reduction of the radius for 128-bond chains. For ring chains evolving without the conservation of linking number, we demonstrate a substantial anti-correlation between the twist and writhe variables whose sum yields the linking number. We raise the possibility that our observed anti-correlations may have counterparts in biomolecules like DNA. We then discuss experiments which combine digital video microscopy and total-internal reflection microscopy (TIRM) in a single technique (3DTIRM) which allows accurate measurement of the three-dimensional location of microscopic particles. We compare two methods for measuring the total scattered light intensity. The first method uses an external photodiode as in conventional TIRM, the second uses only digitized video frames. We employ 3DTIRM to study the material properties of yeast amyloid fibers, consisting of aggregates of Sup35 protein. We attach one end of a biotin-labelled fiber to a glass slide and the other end to a streptavidin-coated 4.4 mum polystyrene sphere. By studying the equilibrium fluctuations of the colloidal sphere, we determine the elastic modulus of the fibers, and set limits on the twisting persistence length.

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

    PubMed

    Sun, Yudong; McKeever, Steve

    2008-01-01

    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. PMID:20134068

  14. Teal Amber Visible Focal Plane Technology

    NASA Astrophysics Data System (ADS)

    Johnson, Charles R.; Burczewski, Ron

    1981-12-01

    Deep-space surveillance missions have imposed severe demands on existing technology and simulated the search for new, advanced technology developments to provide higher performance. Defense Advanced Research Projects Agency (DARPA) sponsored Teal Amber as a visible charge-coupled device (CCD) and associated focal plane signal processing technology development and demonstration program. This paper describes this large-scale, staring-array-sensor concept. The current state of art in the resulting visibled CCD imagers is specified, along with the focal plane signal processor implementation in low power-weight-volume large-scale integrated (LSI) circuitry. Performance requirements and analytic predictions are compared to demonstration system results from an electro-optical test site in White Sands, New Mexico.

  15. Extension of the GLYCAM06 Biomolecular Force Field to Lipids, Lipid Bilayers and Glycolipids.

    PubMed

    Tessier, Matthew B; Demarco, Mari L; Yongye, Austin B; Woods, Robert J

    2008-01-01

    GLYCAM06 is a generalisable biomolecular force field that is extendible to diverse molecular classes in the spirit of a small-molecule force field. Here we report parameters for lipids, lipid bilayers and glycolipids for use with GLYCAM06. Only three lipid-specific atom types have been introduced, in keeping with the general philosophy of transferable parameter development. Bond stretching, angle bending, and torsional force constants were derived by fitting to quantum mechanical data for a collection of minimal molecular fragments and related small molecules. Partial atomic charges were computed by fitting to ensemble-averaged quantum-computed molecular electrostatic potentials.In addition to reproducing quantum mechanical internal rotational energies and experimental valence geometries for an array of small molecules, condensed-phase simulations employing the new parameters are shown to reproduce the bulk physical properties of a DMPC lipid bilayer. The new parameters allow for molecular dynamics simulations of complex systems containing lipids, lipid bilayers, glycolipids, and carbohydrates, using an internally consistent force field. By combining the AMBER parameters for proteins with the GLYCAM06 parameters, it is also possible to simulate protein-lipid complexes and proteins in biologically relevant membrane-like environments. PMID:22247593

  16. The identity of Romanian amber (rumanite) with Baltic amber (succinite).

    SciTech Connect

    Stout, E. C.; Beck, C. W.; Anderson, K. B.; Chemistry; Vassar Coll.

    2000-11-01

    Romanian amber (rumanite) has been considered to be a separate species of fossil resin for more than a century. While earlier investigators held it to be very similar to succinite (Baltic amber), modern scholars have assigned it a distinctly different botanical origin. We have found that almost all of the constituents of the ether-soluble fractions of 13 specimens of authentic rumanite identified by gas chromatography-mass spectrometry have previously been reported in the soluble fraction of succinite, including succinic acid and its monoterpene esters. Additionally and significantly, the soluble fraction of rumanite contains a number defunctionalized compounds that do not preexist in succinite, but that are produced by pyrolysis of whole succinite or of its insoluble polymeric fraction. Simultaneous methylation pyrolysis-gas chromatography-mass spectrometry of the polymeric fraction of seven of the rumanite specimens yielded further copious amounts of dimethyl succinate, a number of diterpene resin acid methyl esters, and additional defunctionalized compounds known to be pyrolysis products of succinite. The evidence shows conclusively that the botanical origin of rumanite is not distinct from that of succinite. Rather, rumanite is a succinite that has suffered partial thermal degradation in the course of the folding of the Oligocene Kliwa sandstone formation in which it is most commonly found.

  17. Extension of the AMBER force field to cyclic α,α dialkylated peptides.

    PubMed

    Grubišić, Sonja; Brancato, Giuseppe; Pedone, Alfonso; Barone, Vincenzo

    2012-11-28

    The popular biomolecular AMBER (ff99SB) force field (FF) has been extended with new parameters for the simulations of peptides containing α,α dialkylated residues with cyclic side chains. Together with the recent set of nitroxide parameters [E. Stendardo, A. Pedone, P. Cimino, M. C. Menziani, O. Crescenzi and V. Barone, Phys. Chem. Chem. Phys., 2010, 12, 11697] this extension allows treating the TOAC residue (TOAC, 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) widely used as a spin label in protein studies. All the conformational minima of the Ac-Ac(6)C-NMe (Ac = acetyl, Ac(6)C = 1-aminocyclohexaneacetic acid, NMe = methylamino) and Ac-TOAC-NMe dipeptides have been examined in terms of geometry and relative energy stability by Quantum Mechanical (QM) computations employing an hybrid density functional (PBE0) for an extended training set of conformers with various folds. A very good agreement between QM and MM (molecular mechanics) data has been obtained in most of the investigated properties, including solvent effects. Finally, the new set of parameters has been validated by comparing the conformational and dynamical behavior of TOAC-labeled polypeptides investigated by means of classical molecular dynamics (MD) simulations with QM data and experimental evidence. The new FF accurately describes the tuning of conformational and dynamical behavior of the Ac-TOAC-NMe dipeptide and double spin-labeled heptapeptide Fmoc-(Aib-Aib-TOAC)(2)-Aib-OMe (Fmoc, fluorenyl-9-methoxycarbonyl; Aib, α-aminoisobutyric acid; OMe, methoxy) by solvents with different polarity. In particular, we found that the 3(10) helical structure of heptapeptide is the most stable one in vacuo, with a geometry very similar to the X-ray crystallographic structure, whereas a conformational equilibrium between the 3(10)- and α-helical structures is established in aqueous solution, in agreement with EPR data. PMID:23051698

  18. Foundations of Biomolecular Modeling

    PubMed Central

    Jorgensen, William L.

    2014-01-01

    The 2013 Nobel Prize in Chemistry has been awarded to Martin Kaplus, Michael Levitt, and Arieh Warshel for “Development of Multiscale Models for Complex Chemical Systems”. The honored work from the 1970s has provided a foundation for the widespread activities today in modeling organic and biomolecular systems. PMID:24315087

  19. Technology for melting amber chips to produce a solid block

    NASA Astrophysics Data System (ADS)

    Vikhareva, A. S.; Melnikov, A. G.; Utyev, O. M.

    2016-04-01

    This research is relevant, because the bulk of the mined amber comes in amber chips. Therefore, we have decided to review the current ways of melting amber chips to develop the most technologically efficient algorithm and to use it further for producing decorative items. The purpose of the work is to perfect the technology of obtaining whole-piece amber from amber chips and to explore the usability of the obtained material in decorative items and jewelry.

  20. ORAC: a molecular dynamics simulation program to explore free energy surfaces in biomolecular systems at the atomistic level.

    PubMed

    Marsili, Simone; Signorini, Giorgio Federico; Chelli, Riccardo; Marchi, Massimo; Procacci, Piero

    2010-04-15

    We present the new release of the ORAC engine (Procacci et al., Comput Chem 1997, 18, 1834), a FORTRAN suite to simulate complex biosystems at the atomistic level. The previous release of the ORAC code included multiple time steps integration, smooth particle mesh Ewald method, constant pressure and constant temperature simulations. The present release has been supplemented with the most advanced techniques for enhanced sampling in atomistic systems including replica exchange with solute tempering, metadynamics and steered molecular dynamics. All these computational technologies have been implemented for parallel architectures using the standard MPI communication protocol. ORAC is an open-source program distributed free of charge under the GNU general public license (GPL) at http://www.chim.unifi.it/orac. PMID:19824035

  1. Palaeontology: Chinese amber insects bridge the gap.

    PubMed

    Ross, Andrew

    2014-07-21

    n the study of fossil insects, Chinese amber from Fushun has been largely overlooked. A new study now reveals a highly diverse biota and provides a wealth of new information on the past Asian insect fauna. PMID:25050958

  2. Optical characterization of amber from Chiapas, Mexico

    NASA Astrophysics Data System (ADS)

    López-Morales, Guadalupe; Espinosa-Luna, Rafael; Frausto-Reyes, Claudio

    2013-09-01

    An optical characterization of amber samples from México, the Baltic Sea and fake samples is presented, with the aim of discriminate between genuine and fake samples. We sought to identify the physical variables that could serve as the basis for the development of a device whose operation was able to discriminate between samples of genuine and fake amber. The optical refractive index was determined by Spectroscopic Ellipsometry, Abbe refractometry, and by the Brewster angle. The Raman spectra and the fluorescence optical responses were also determined. The results obtained indicate that the refractive index is not a robust variable that can differentiate between genuine amber and a fake sample. On the other hand, the Raman spectra and the fluorescence responses provide information that allows discriminating between both types of samples. For this reason, we used the results obtained by fluorescence as a basis for the design and construction of a prototype simple, reliable, portable, and affordable for authentication of the Mexican amber.

  3. Thermodynamic properties of water solvating biomolecular surfaces

    NASA Astrophysics Data System (ADS)

    Heyden, Matthias

    Changes in the potential energy and entropy of water molecules hydrating biomolecular interfaces play a significant role for biomolecular solubility and association. Free energy perturbation and thermodynamic integration methods allow calculations of free energy differences between two states from simulations. However, these methods are computationally demanding and do not provide insights into individual thermodynamic contributions, i.e. changes in the solvent energy or entropy. Here, we employ methods to spatially resolve distributions of hydration water thermodynamic properties in the vicinity of biomolecular surfaces. This allows direct insights into thermodynamic signatures of the hydration of hydrophobic and hydrophilic solvent accessible sites of proteins and small molecules and comparisons to ideal model surfaces. We correlate dynamic properties of hydration water molecules, i.e. translational and rotational mobility, to their thermodynamics. The latter can be used as a guide to extract thermodynamic information from experimental measurements of site-resolved water dynamics. Further, we study energy-entropy compensations of water at different hydration sites of biomolecular surfaces. This work is supported by the Cluster of Excellence RESOLV (EXC 1069) funded by the Deutsche Forschungsgemeinschaft.

  4. Amber Plug-In for Protein Shop

    Energy Science and Technology Software Center (ESTSC)

    2004-05-10

    The Amber Plug-in for ProteinShop has two main components: an AmberEngine library to compute the protein energy models, and a module to solve the energy minimization problem using an optimization algorithm in the OPTI-+ library. Together, these components allow the visualization of the protein folding process in ProteinShop. AmberEngine is a object-oriented library to compute molecular energies based on the Amber model. The main class is called ProteinEnergy. Its main interface methods are (1) "init"more » to initialize internal variables needed to compute the energy. (2) "eval" to evaluate the total energy given a vector of coordinates. Additional methods allow the user to evaluate the individual components of the energy model (bond, angle, dihedral, non-bonded-1-4, and non-bonded energies) and to obtain the energy of each individual atom. The Amber Engine library source code includes examples and test routines that illustrate the use of the library in stand alone programs. The energy minimization module uses the AmberEngine library and the nonlinear optimization library OPT++. OPT++ is open source software available under the GNU Lesser General Public License. The minimization module currently makes use of the LBFGS optimization algorithm in OPT++ to perform the energy minimization. Future releases may give the user a choice of other algorithms available in OPT++.« less

  5. Improved Parameterization of Amine-Carboxylate and Amine-Phosphate Interactions for Molecular Dynamics Simulations Using the CHARMM and AMBER Force Fields.

    PubMed

    Yoo, Jejoong; Aksimentiev, Aleksei

    2016-01-12

    Over the past decades, molecular dynamics (MD) simulations of biomolecules have become a mainstream biophysics technique. As the length and time scales amenable to the MD method increase, shortcomings of the empirical force fields, which have been developed and validated using relatively short simulations of small molecules, become apparent. One common artifact is aggregation of water-soluble biomolecules driven by artificially strong charge-charge interactions. Here, we report a systematic atom pair-specific refinement of Lennard-Jones parameters (NBFIX) describing amine-carboxylate and amine-phosphate interactions, which bring MD simulations of basic peptide-mediated nucleic acid assemblies and lipid bilayer membranes into better agreement with experimental data. As our refinement does not affect the existing parametrization of bonded interactions or alter the solvation free energies, it improves the realism of an MD simulation without introducing additional artifacts. PMID:26632962

  6. NMscatt: a program for calculating inelastic scattering from large biomolecular systems using classical force-field simulations

    NASA Astrophysics Data System (ADS)

    Merzel, Franci; Fontaine-Vive, Fabien; Johnson, Mark R.

    2007-09-01

    Computational tools for normal mode analysis, which are widely used in physics and materials science problems, are designed here in a single package called NMscatt (Normal Modes & scattering) that allows arbitrarily large systems to be handled. The package allows inelastic neutron and X-ray scattering observables to be calculated, allowing comparison with experimental data produced at large scale facilities. Various simplification schemes are presented for analyzing displacement vectors, which are otherwise too complicated to understand in very large systems. Program summaryTitle of program:NMscatt Catalogue identifier:ADZA_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADZA_v1_0.html Program obtainable from:CPC Program Library, Queen's University of Belfast, N. Ireland Licensing provisions:no No. of lines in distributed program, including test data, etc.:573 535 No. of bytes in distributed program, including test data, etc.:4 516 496 Distribution format:tar.gz Programming language:FORTRAN 77 Computer:x86 PC Operating system:GNU/Linux, UNIX RAM:Depends on the system size to be simulated Word size:32 or 64 bits Classification:16.3 External routines:LAPACK Nature of problem: Normal mode analysis, phonons calculation, derivation of incoherent and coherent inelastic scattering spectra. Solution method: Full diagonalization (producing eigen-vectors and eigen-values) of dynamical matrix which is obtained from potential energy function derivation using finite difference method. Running time: About 7 hours per one k-point evaluation in sampling all modes dispersion curves for a system containing 3550 atoms in the unit cell on AMD Athlon 64 X2 Dual Core Processor 4200+.

  7. Carnivorous leaves from Baltic amber

    PubMed Central

    Sadowski, Eva-Maria; Seyfullah, Leyla J.; Sadowski, Friederike; Fleischmann, Andreas; Behling, Hermann; Schmidt, Alexander R.

    2015-01-01

    The fossil record of carnivorous plants is very scarce and macrofossil evidence has been restricted to seeds of the extant aquatic genus Aldrovanda of the Droseraceae family. No case of carnivorous plant traps has so far been reported from the fossil record. Here, we present two angiosperm leaves enclosed in a piece of Eocene Baltic amber that share relevant morphological features with extant Roridulaceae, a carnivorous plant family that is today endemic to the Cape flora of South Africa. Modern Roridula species are unique among carnivorous plants as they digest prey in a complex mutualistic association in which the prey-derived nutrient uptake depends on heteropteran insects. As in extant Roridula, the fossil leaves possess two types of plant trichomes, including unicellular hairs and five size classes of multicellular stalked glands (or tentacles) with an apical pore. The apices of the narrow and perfectly tapered fossil leaves end in a single tentacle, as in both modern Roridula species. The glandular hairs of the fossils are restricted to the leaf margins and to the abaxial lamina, as in extant Roridula gorgonias. Our discovery supports current molecular age estimates for Roridulaceae and suggests a wide Eocene distribution of roridulid plants. PMID:25453067

  8. Carnivorous leaves from Baltic amber.

    PubMed

    Sadowski, Eva-Maria; Seyfullah, Leyla J; Sadowski, Friederike; Fleischmann, Andreas; Behling, Hermann; Schmidt, Alexander R

    2015-01-01

    The fossil record of carnivorous plants is very scarce and macrofossil evidence has been restricted to seeds of the extant aquatic genus Aldrovanda of the Droseraceae family. No case of carnivorous plant traps has so far been reported from the fossil record. Here, we present two angiosperm leaves enclosed in a piece of Eocene Baltic amber that share relevant morphological features with extant Roridulaceae, a carnivorous plant family that is today endemic to the Cape flora of South Africa. Modern Roridula species are unique among carnivorous plants as they digest prey in a complex mutualistic association in which the prey-derived nutrient uptake depends on heteropteran insects. As in extant Roridula, the fossil leaves possess two types of plant trichomes, including unicellular hairs and five size classes of multicellular stalked glands (or tentacles) with an apical pore. The apices of the narrow and perfectly tapered fossil leaves end in a single tentacle, as in both modern Roridula species. The glandular hairs of the fossils are restricted to the leaf margins and to the abaxial lamina, as in extant Roridula gorgonias. Our discovery supports current molecular age estimates for Roridulaceae and suggests a wide Eocene distribution of roridulid plants. PMID:25453067

  9. Biomolecular visualization using AVS.

    PubMed

    Duncan, B S; Macke, T J; Olson, A J

    1995-10-01

    Dataflow systems for scientific visualization are becoming increasingly sophisticated in their architecture and functionality. AVS, from Advanced Visual Systems Inc., is a powerful dataflow environment that has been applied to many computation and visualization tasks. An important, yet complex, application area is molecular modeling and biomolecular visualization. Problems in biomolecular visualization tax the capability of dataflow systems because of the diversity of operations that are required and because many operations do not fit neatly into the dataflow paradigm. Here we describe visualization strategies and auxiliary programs developed to enhance the applicability of AVS for molecular modelling. Our visualization strategy is to use general-purpose AVS modules and a small number of chemistry-specific modules. We have developed methods to control AVS using AVS-tool, a programmable interface to the AVS Command Line Interpreter (CLI), and have also developed NAB, a C-like language for writing AVS modules that has extensions for operating on proteins and nucleic acids. This strategy provides a flexible and extensible framework for a wide variety of molecular modeling tasks. PMID:8603055

  10. Arthropods in amber from the Triassic Period

    PubMed Central

    Schmidt, Alexander R.; Jancke, Saskia; Lindquist, Evert E.; Ragazzi, Eugenio; Roghi, Guido; Nascimbene, Paul C.; Schmidt, Kerstin; Wappler, Torsten; Grimaldi, David A.

    2012-01-01

    The occurrence of arthropods in amber exclusively from the Cretaceous and Cenozoic is widely regarded to be a result of the production and preservation of large amounts of tree resin beginning ca. 130 million years (Ma) ago. Abundant 230 million-year-old amber from the Late Triassic (Carnian) of northeastern Italy has previously yielded myriad microorganisms, but we report here that it also preserves arthropods some 100 Ma older than the earliest prior records in amber. The Triassic specimens are a nematoceran fly (Diptera) and two disparate species of mites, Triasacarus fedelei gen. et sp. nov., and Ampezzoa triassica gen. et sp. nov. These mites are the oldest definitive fossils of a group, the Eriophyoidea, which includes the gall mites and comprises at least 3,500 Recent species, 97% of which feed on angiosperms and represents one of the most specialized lineages of phytophagous arthropods. Antiquity of the gall mites in much their extant form was unexpected, particularly with the Triassic species already having many of their present-day features (such as only two pairs of legs); further, it establishes conifer feeding as an ancestral trait. Feeding by the fossil mites may have contributed to the formation of the amber droplets, but we find that the abundance of amber during the Carnian (ca. 230 Ma) is globally anomalous for the pre-Cretaceous and may, alternatively, be related to paleoclimate. Further recovery of arthropods in Carnian-aged amber is promising and will have profound implications for understanding the evolution of terrestrial members of the most diverse phylum of organisms. PMID:22927387

  11. Arthropods in amber from the Triassic Period.

    PubMed

    Schmidt, Alexander R; Jancke, Saskia; Lindquist, Evert E; Ragazzi, Eugenio; Roghi, Guido; Nascimbene, Paul C; Schmidt, Kerstin; Wappler, Torsten; Grimaldi, David A

    2012-09-11

    The occurrence of arthropods in amber exclusively from the Cretaceous and Cenozoic is widely regarded to be a result of the production and preservation of large amounts of tree resin beginning ca. 130 million years (Ma) ago. Abundant 230 million-year-old amber from the Late Triassic (Carnian) of northeastern Italy has previously yielded myriad microorganisms, but we report here that it also preserves arthropods some 100 Ma older than the earliest prior records in amber. The Triassic specimens are a nematoceran fly (Diptera) and two disparate species of mites, Triasacarus fedelei gen. et sp. nov., and Ampezzoa triassica gen. et sp. nov. These mites are the oldest definitive fossils of a group, the Eriophyoidea, which includes the gall mites and comprises at least 3,500 Recent species, 97% of which feed on angiosperms and represents one of the most specialized lineages of phytophagous arthropods. Antiquity of the gall mites in much their extant form was unexpected, particularly with the Triassic species already having many of their present-day features (such as only two pairs of legs); further, it establishes conifer feeding as an ancestral trait. Feeding by the fossil mites may have contributed to the formation of the amber droplets, but we find that the abundance of amber during the Carnian (ca. 230 Ma) is globally anomalous for the pre-Cretaceous and may, alternatively, be related to paleoclimate. Further recovery of arthropods in Carnian-aged amber is promising and will have profound implications for understanding the evolution of terrestrial members of the most diverse phylum of organisms. PMID:22927387

  12. An opilioacarid mite in Cretaceous Burmese amber

    NASA Astrophysics Data System (ADS)

    Dunlop, Jason A.; de Oliveira Bernardi, Leopoldo Ferreira

    2014-09-01

    A fossil opilioacarid mite (Parasitiformes: Opilioacarida) in Burmese amber is described as ? Opilioacarus groehni sp. nov. This ca. 99 Ma record (Upper Cretaceous: Cenomanian) represents only the third fossil example of this putatively basal mite lineage, the others originating from Eocene Baltic amber (ca. 44-49 Ma). Our new record is not only the oldest record of Opilioacarida, but it is also one of the oldest examples of the entire Parasitiformes clade. The presence of Opilioacarida—potentially Opiloacarus—in the Cretaceous of SE Asia suggests that some modern genus groups were formerly more widely distributed across the northern hemisphere, raising questions about previously suggested Gondwanan origins for these mites.

  13. Experiments in Biomolecular Computing

    NASA Astrophysics Data System (ADS)

    Kaplan, Peter; Cecchi, Guillermo; Libchaber, Albert

    1996-03-01

    We review our experiments on computing with DNA(L. M. Adleman, Science) 266, 1021 (1994)., presenting findings about the technologies that will be required to make biomolecular computing useful. The advantages of using DNA for molecular computation include large information density (> 1 terabyte/mm^3), massive parallelism, and the existence of tools (enzymes) with which to manipulate the molecules. The major disadvantage is the slow cycle time (hours per biochemical step). The only demonstrated DNA computing algorithm involves first producing a pool of DNA containing all possible answers to a combinatorial question and then searching in that pool for the correct answer. We will discuss new work on the technical details of the polymerase chain reaction (PCR), a DNA amplifier, and on the construction of the pool of DNA from which the correct answer will be extracted.

  14. GENESIS: a hybrid-parallel and multi-scale molecular dynamics simulator with enhanced sampling algorithms for biomolecular and cellular simulations

    PubMed Central

    Jung, Jaewoon; Mori, Takaharu; Kobayashi, Chigusa; Matsunaga, Yasuhiro; Yoda, Takao; Feig, Michael; Sugita, Yuji

    2015-01-01

    GENESIS (Generalized-Ensemble Simulation System) is a new software package for molecular dynamics (MD) simulations of macromolecules. It has two MD simulators, called ATDYN and SPDYN. ATDYN is parallelized based on an atomic decomposition algorithm for the simulations of all-atom force-field models as well as coarse-grained Go-like models. SPDYN is highly parallelized based on a domain decomposition scheme, allowing large-scale MD simulations on supercomputers. Hybrid schemes combining OpenMP and MPI are used in both simulators to target modern multicore computer architectures. Key advantages of GENESIS are (1) the highly parallel performance of SPDYN for very large biological systems consisting of more than one million atoms and (2) the availability of various REMD algorithms (T-REMD, REUS, multi-dimensional REMD for both all-atom and Go-like models under the NVT, NPT, NPAT, and NPγT ensembles). The former is achieved by a combination of the midpoint cell method and the efficient three-dimensional Fast Fourier Transform algorithm, where the domain decomposition space is shared in real-space and reciprocal-space calculations. Other features in SPDYN, such as avoiding concurrent memory access, reducing communication times, and usage of parallel input/output files, also contribute to the performance. We show the REMD simulation results of a mixed (POPC/DMPC) lipid bilayer as a real application using GENESIS. GENESIS is released as free software under the GPLv2 licence and can be easily modified for the development of new algorithms and molecular models. WIREs Comput Mol Sci 2015, 5:310–323. doi: 10.1002/wcms.1220 PMID:26753008

  15. VFFDT: A New Software for Preparing AMBER Force Field Parameters for Metal-Containing Molecular Systems.

    PubMed

    Zheng, Suqing; Tang, Qing; He, Jian; Du, Shiyu; Xu, Shaofang; Wang, Chaojie; Xu, Yong; Lin, Fu

    2016-04-25

    Force fields are fundamental to molecular dynamics simulations. However, the incompleteness of force field parameters has been a long-standing problem, especially for metal-related systems. In our previous work, we adopted the Seminario method based on the Hessian matrix to systematically derive the zinc-related force field parameters for AMBER. In this work, in order to further simplify the whole protocol, we have implemented a user-friendly Visual Force Field Derivation Toolkit (VFFDT) to derive the force field parameters via simply clicking on the bond or angle in the 3D viewer, and we have further extended our previous program to support the Hessian matrix output from a variety of quantum mechanics (QM) packages, including Gaussian 03/09, ORCA 3.0, QChem, GAMESS-US, and MOPAC 2009/2012. In this toolkit, a universal VFFDT XYZ file format containing the raw Hessian matrix is available for all of the QM packages, and an instant force field parametrization protocol based on a semiempirical quantum mechanics (SQM) method is introduced. The new function that can automatically obtain the relevant parameters for zinc, copper, iron, etc., which can be exported in AMBER Frcmod format, has been added. Furthermore, our VFFDT program can read and write files in AMBER Prepc, AMBER Frcmod, and AMBER Mol2 format and can also be used to customize, view, copy, and paste the force field parameters in the context of the 3D viewer, which provides utilities complementary to ANTECHAMBER, MCPB, and MCPB.py in the AmberTools. PMID:26998926

  16. Penis morphology in a Burmese amber harvestman.

    PubMed

    Dunlop, Jason A; Selden, Paul A; Giribet, Gonzalo

    2016-02-01

    A unique specimen of the fossil harvestman Halitherses grimaldii Giribet and Dunlop, 2005 (Arachnida: Opiliones) from the Cretaceous (ca. 99 Ma) Burmese amber of Myanmar reveals a fully extended penis. This is the first record of a male copulatory organ of this nature preserved in amber and is of special importance due to the age of the deposit. The penis has a slender, distally flattened truncus, a spatulate heart-shaped glans and a short distal stylus, twisted at the tip. In living harvestmen, the penis yields crucial characters for their systematics. Male genital morphology in H. grimaldii appears to be unique among the wider Dyspnoi clade to which this fossil belongs. The large eyes in the fossil differ markedly from other members of the subfamily Ortholasmatinae to which H. grimaldii was originally referred. Based on recent data, it has been argued that large eyes may be plesiomorphic for Palpatores (i.e. the suborders Eupnoi and Dyspnoi), potentially rendering this character plesiomorphic for the fossil too. Thus, the unique structure of the penis seen here, and the probable lack of diaphanous teeth, present in all other extant non-acropsopilionid Dyspnoi, suggest that H. grimaldii represents a new, extinct family of large-eyed dyspnoid harvestmen, Halithersidae fam. nov.; a higher taxon in amber diagnosed here on both somatic and genital characters. PMID:26820298

  17. Penis morphology in a Burmese amber harvestman

    NASA Astrophysics Data System (ADS)

    Dunlop, Jason A.; Selden, Paul A.; Giribet, Gonzalo

    2016-02-01

    A unique specimen of the fossil harvestman Halitherses grimaldii Giribet and Dunlop, 2005 (Arachnida: Opiliones) from the Cretaceous (ca. 99 Ma) Burmese amber of Myanmar reveals a fully extended penis. This is the first record of a male copulatory organ of this nature preserved in amber and is of special importance due to the age of the deposit. The penis has a slender, distally flattened truncus, a spatulate heart-shaped glans and a short distal stylus, twisted at the tip. In living harvestmen, the penis yields crucial characters for their systematics. Male genital morphology in H. grimaldii appears to be unique among the wider Dyspnoi clade to which this fossil belongs. The large eyes in the fossil differ markedly from other members of the subfamily Ortholasmatinae to which H. grimaldii was originally referred. Based on recent data, it has been argued that large eyes may be plesiomorphic for Palpatores (i.e. the suborders Eupnoi and Dyspnoi), potentially rendering this character plesiomorphic for the fossil too. Thus, the unique structure of the penis seen here, and the probable lack of diaphanous teeth, present in all other extant non-acropsopilionid Dyspnoi, suggest that H. grimaldii represents a new, extinct family of large-eyed dyspnoid harvestmen, Halithersidae fam. nov.; a higher taxon in amber diagnosed here on both somatic and genital characters.

  18. Three-dimensional molecular theory of solvation coupled with molecular dynamics in Amber

    PubMed Central

    Luchko, Tyler; Gusarov, Sergey; Roe, Daniel R.; Simmerling, Carlos; Case, David A.; Tuszynski, Jack; Kovalenko, Andriy

    2010-01-01

    We present the three-dimensional molecular theory of solvation (also known as 3D-RISM) coupled with molecular dynamics (MD) simulation by contracting solvent degrees of freedom, accelerated by extrapolating solvent-induced forces and applying them in large multi-time steps (up to 20 fs) to enable simulation of large biomolecules. The method has been implemented in the Amber molecular modeling package, and is illustrated here on alanine dipeptide and protein G. PMID:20440377

  19. First early Mesozoic amber in the Western Hemisphere

    NASA Astrophysics Data System (ADS)

    Litwin, Ronald J.; Ash, Sidney R.

    1991-03-01

    Detrital amber pebbles and granules have been discovered in Upper Triassic strata on the Colorado Plateau. Although amber pre-viously has been reported from Pennsylvanian, Jurassic, Cretaceous, and Tertiary strata, we know of no other reported Triassic occurrence in North America or the Western Hemisphere. The newly discovered occurrences of amber are at two localities in the lower part of the Petrified }Forest Member of the Upper Triassic Chinle Formation in Petrified Forest National Park, Arizona. The paper coals and carbonaceous paper shales containing the amber also contain fossil palynomorph assemblages that indicate a late Carnian age for these occurrences.

  20. Improvements in continuum modeling for biomolecular systems

    NASA Astrophysics Data System (ADS)

    Yu, Qiao; Ben-Zhuo, Lu

    2016-01-01

    Modeling of biomolecular systems plays an essential role in understanding biological processes, such as ionic flow across channels, protein modification or interaction, and cell signaling. The continuum model described by the Poisson- Boltzmann (PB)/Poisson-Nernst-Planck (PNP) equations has made great contributions towards simulation of these processes. However, the model has shortcomings in its commonly used form and cannot capture (or cannot accurately capture) some important physical properties of the biological systems. Considerable efforts have been made to improve the continuum model to account for discrete particle interactions and to make progress in numerical methods to provide accurate and efficient simulations. This review will summarize recent main improvements in continuum modeling for biomolecular systems, with focus on the size-modified models, the coupling of the classical density functional theory and the PNP equations, the coupling of polar and nonpolar interactions, and numerical progress. Project supported by the National Natural Science Foundation of China (Grant No. 91230106) and the Chinese Academy of Sciences Program for Cross & Cooperative Team of the Science & Technology Innovation.

  1. Markov state models of biomolecular conformational dynamics

    PubMed Central

    Chodera, John D.; Noé, Frank

    2014-01-01

    It has recently become practical to construct Markov state models (MSMs) that reproduce the long-time statistical conformational dynamics of biomolecules using data from molecular dynamics simulations. MSMs can predict both stationary and kinetic quantities on long timescales (e.g. milliseconds) using a set of atomistic molecular dynamics simulations that are individually much shorter, thus addressing the well-known sampling problem in molecular dynamics simulation. In addition to providing predictive quantitative models, MSMs greatly facilitate both the extraction of insight into biomolecular mechanism (such as folding and functional dynamics) and quantitative comparison with single-molecule and ensemble kinetics experiments. A variety of methodological advances and software packages now bring the construction of these models closer to routine practice. Here, we review recent progress in this field, considering theoretical and methodological advances, new software tools, and recent applications of these approaches in several domains of biochemistry and biophysics, commenting on remaining challenges. PMID:24836551

  2. Surface topography dependence of biomolecular hydrophobic hydration

    NASA Astrophysics Data System (ADS)

    Cheng, Yuen-Kit; Rossky, Peter J.

    1998-04-01

    Many biomolecules are characterized by surfaces containing extended nonpolar regions, and the aggregation and subsequent removal of such surfaces from water is believed to play a critical role in the biomolecular assembly in cells. A better understanding of the hydrophobic hydration of biomolecules may therefore yield new insights into intracellular assembly. Conventional views hold that the hydration shell of small hydrophobic solutes is clathrate-like, characterized by local cage-like hydrogen-bonding structures and a distinct loss in entropy. The hydration of extended nonpolar planar surfaces, however, appears to involve structures that are orientationally inverted relative to clathrate-like hydration shells,, with unsatisfied hydrogen bonds that are directed towards the hydrophobic surface. Here we present computer simulations of the interaction between the polypeptide melittin and water that demonstrate that the two different hydration structures also exist near a biomolecular surface. We find that the two structures are distinguished by a substantial difference in the water-water interaction enthalpy, and that their relative contributions depend strongly on the surface topography of the melittin molecule: clathrate-like structures dominate near convex surface patches, whereas the hydration shell near flat surfaces fluctuates between clathrate-like and less-ordered or inverted structures. The strong influence of surface topography on the structure and free energy of hydrophobic hydration is likely to hold in general, and will be particularly important for the many biomolecules whose surfaces contain convex patches, deep or shallow concave grooves and roughly planar areas.

  3. Raman microspectroscopic studies of amber resins with insect inclusions

    NASA Astrophysics Data System (ADS)

    Edwards, Howell G. M.; Farwell, Dennis W.; Villar, Susana E. Jorge

    2007-12-01

    Raman microscope spectra of specimens of Baltic and Mexican amber resins containing insect inclusions have been analysed using near-infrared excitation to assess the potential for discrimination between the keratotic remains of the insects and the terpenoid matrix. For the Mexican amber specimen the insect spectra exhibit evidence of significant protein degradation compared with the insect remains in the Baltic amber specimen. In both cases the Raman spectra of the insect remains are still distinguishable from the amber resins. Despite its better preservation, however, no spectra could be obtained from the inside of the larger insect preserved in the Baltic amber in agreement with the observation that most insect inclusions in amber are hollow. It is noted that the Mexican amber insect is located adjacent to a large gas bubble in the amber matrix, to which the observed degradation of the insect and its poor state of preservation are attributed. It is concluded that Raman spectra of insect inclusions can provide useful information about the chemical composition of the remains and that confocal microscopy is particularly advantageous in this respect.

  4. Molecular dynamics simulation of triclinic lysozyme in a crystal lattice.

    PubMed

    Janowski, Pawel A; Liu, Chunmei; Deckman, Jason; Case, David A

    2016-01-01

    Molecular dynamics simulations of crystals can enlighten interpretation of experimental X-ray crystallography data and elucidate structural dynamics and heterogeneity in biomolecular crystals. Furthermore, because of the direct comparison against experimental data, they can inform assessment of molecular dynamics methods and force fields. We present microsecond scale results for triclinic hen egg-white lysozyme in a supercell consisting of 12 independent unit cells using four contemporary force fields (Amber ff99SB, ff14ipq, ff14SB, and CHARMM 36) in crystalline and solvated states (for ff14SB only). We find the crystal simulations consistent across multiple runs of the same force field and robust to various solvent equilibration schemes. However, convergence is slow compared with solvent simulations. All the tested force fields reproduce experimental structural and dynamic properties well, but Amber ff14SB maintains structure and reproduces fluctuations closest to the experimental model: its average backbone structure differs from the deposited structure by 0.37Å; by contrast, the average backbone structure in solution differs from the deposited by 0.65Å. All the simulations are affected by a small progressive deterioration of the crystal lattice, presumably due to imperfect modeling of hydrogen bonding and other crystal contact interactions; this artifact is smallest in ff14SB, with average lattice positions deviating by 0.20Å from ideal. Side-chain disorder is surprisingly low with fewer than 30% of the nonglycine or alanine residues exhibiting significantly populated alternate rotamers. Our results provide helpful insight into the methodology of biomolecular crystal simulations and indicate directions for future work to obtain more accurate energy models for molecular dynamics. PMID:26013419

  5. Lightweight Object Oriented Structure analysis: Tools for building Tools to Analyze Molecular Dynamics Simulations

    PubMed Central

    Romo, Tod D.; Leioatts, Nicholas; Grossfield, Alan

    2014-01-01

    LOOS (Lightweight Object-Oriented Structure-analysis) is a C++ library designed to facilitate making novel tools for analyzing molecular dynamics simulations by abstracting out the repetitive tasks, allowing developers to focus on the scientifically relevant part of the problem. LOOS supports input using the native file formats of most common biomolecular simulation packages, including CHARMM, NAMD, Amber, Tinker, and Gromacs. A dynamic atom selection language based on the C expression syntax is included and is easily accessible to the tool-writer. In addition, LOOS is bundled with over 120 pre-built tools, including suites of tools for analyzing simulation convergence, 3D histograms, and elastic network models. Through modern C++ design, LOOS is both simple to develop with (requiring knowledge of only 4 core classes and a few utility functions) and is easily extensible. A python interface to the core classes is also provided, further facilitating tool development. PMID:25327784

  6. Mammalian hairs in Early Cretaceous amber

    NASA Astrophysics Data System (ADS)

    Vullo, Romain; Girard, Vincent; Azar, Dany; Néraudeau, Didier

    2010-07-01

    Two mammalian hairs have been found in association with an empty puparium in a ˜100-million-year-old amber (Early Cretaceous) from France. Although hair is known to be an ancestral, ubiquitous feature in the crown Mammalia, the structure of Mesozoic hair has never been described. In contrast to fur and hair of some Jurassic and Cretaceous mammals preserved as carbonized filaments, the exceptional preservation of the fossils described here allows for the study of the cuticular structure. Results show the oldest direct evidence of hair with a modern scale pattern. This discovery implies that the morphology of hair cuticula may have remained unchanged throughout most of mammalian evolution. The association of these hairs with a possible fly puparium provides paleoecological information and indicates peculiar taphonomic conditions.

  7. Stochastic computing with biomolecular automata

    NASA Astrophysics Data System (ADS)

    Adar, Rivka; Benenson, Yaakov; Linshiz, Gregory; Rosner, Amit; Tishby, Naftali; Shapiro, Ehud

    2004-07-01

    Stochastic computing has a broad range of applications, yet electronic computers realize its basic step, stochastic choice between alternative computation paths, in a cumbersome way. Biomolecular computers use a different computational paradigm and hence afford novel designs. We constructed a stochastic molecular automaton in which stochastic choice is realized by means of competition between alternative biochemical pathways, and choice probabilities are programmed by the relative molar concentrations of the software molecules coding for the alternatives. Programmable and autonomous stochastic molecular automata have been shown to perform direct analysis of disease-related molecular indicators in vitro and may have the potential to provide in situ medical diagnosis and cure.

  8. An asterid flower from neotropical mid-Tertiary amber.

    PubMed

    Poinar, George O; Struwe, Lena

    2016-01-01

    Fossils preserved in amber may provide significant palaeoevolutionary and biogeographical data regarding the evolution of life on Earth(1). Although amber is particularly noted for its detailed preservation of arthropods, the same degree of preservation can be found for vascular plant remains(2). Mid-Tertiary Dominican amber is a rich source for such fossils, and representatives of several angiosperm families have been described. However, no fossilized examples of the large asterid plant clade have yet been reported. Here we describe the first fossil neotropical flowers found in amber from a representative of the asterids. The asterids are one of the largest lineages of flowering plants, containing groups such as the sunflower, potato, coffee and mint families, totalling over 80,000 species(3). The new fossils are only known as flowers, more precisely corollas with stamens and styles. We here describe them as a new species, Strychnos electri sp. nov, in the plant family Loganiaceae (Gentianales). PMID:27249345

  9. E9-Im9 Colicin DNase−Immunity Protein Biomolecular Association in Water: A Multiple-Copy and Accelerated Molecular Dynamics Simulation Study

    PubMed Central

    2008-01-01

    Protein−protein transient and dynamic interactions underlie all biological processes. The molecular dynamics (MD) of the E9 colicin DNase protein, its Im9 inhibitor protein, and their E9-Im9 recognition complex are investigated by combining multiple-copy (MC) MD and accelerated MD (aMD) explicit-solvent simulation approaches, after validation with crystalline-phase and solution experiments. Im9 shows higher flexibility than its E9 counterpart. Im9 displays a significant reduction of backbone flexibility and a remarkable increase in motional correlation upon E9 association. Im9 loops 23−31 and 54−64 open with respect to the E9-Im9 X-ray structure and show high conformational diversity. Upon association a large fraction (∼20 nm2) of E9 and Im9 protein surfaces become inaccessible to water. Numerous salt bridges transiently occurring throughout our six 50 ns long MC-MD simulations are not present in the X-ray model. Among these Im9 Glu31−E9 Arg96 and Im9 Glu41−Lys89 involve interface interactions. Through the use of 10 ns of Im9 aMD simulation, we reconcile the largest thermodynamic impact measured for Asp51Ala mutation with Im9 structure and dynamics. Lys57 acts as an essential molecular switch to shift Im9 surface loop towards an ideal configuration for E9 inhibition. This is achieved by switching Asp60−Lys57 and Asp62−Lys57 hydrogen bonds to Asp51−Lys57 salt bridge. E9-Im9 recognition involves shifts of conformational distributions, reorganization of intramolecular hydrogen bond patterns, and formation of new inter- and intramolecular interactions. The description of key transient biological interactions can be significantly enriched by the dynamic and atomic-level information provided by computer simulations. PMID:19053689

  10. An Assembly Funnel Makes Biomolecular Complex Assembly Efficient

    PubMed Central

    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

  11. AMBER: a PIC slice code for DARHT

    NASA Astrophysics Data System (ADS)

    Vay, Jean-Luc; Fawley, William

    1999-11-01

    The accelerator for the second axis of the Dual Axis Radiographic Hydrodynamic Test (DARHT) facility will produce a 4-kA, 20-MeV, 2-μ s output electron beam with a design goal of less than 1000 π mm-mrad normalized transverse emittance and less than 0.5-mm beam centroid motion. In order to study the beam dynamics throughout the accelerator, we have developed a slice Particle-In-Cell code named AMBER, in which the beam is modeled as a time-steady flow, subject to self, as well as external, electrostatic and magnetostatic fields. The code follows the evolution of a slice of the beam as it propagates through the DARHT accelerator lattice, modeled as an assembly of pipes, solenoids and gaps. In particular, we have paid careful attention to non-paraxial phenomena that can contribute to nonlinear forces and possible emittance growth. We will present the model and the numerical techniques implemented, as well as some test cases and some preliminary results obtained when studying emittance growth during the beam propagation.

  12. Incoporating Existing Large Applications in the PUPIL System: Amber

    NASA Astrophysics Data System (ADS)

    Trickey, Sam; Torras Costa, Juan; Seabra, Gustavo De Miranda; Roitberg, Adrian; Deumens, E.

    2007-03-01

    PUPIL (Program for User Package Interfacing and Linking)^1 inter-operates existing codes for multi-threaded, multi-scale quantum and classical mechanical simulations via JAVA, XML, JAVA, a C++ library, and minimally intrusive wrappers for each code. An architectural challenge for PUPIL is support of modules from a multi-scale QM-MD suite with much internal coupling. We have succeeded with the AMBER suite MD module (Sander), with Gaussian03 for QM. Our demonstration study is the decomposition of Angelis' salt with explict water. A variable quantum zone (solute and first solvation cell) was used, with the remaining waters via TIP3P. Sander calculated the Potential of Mean Force for the reaction through umbrella sampling, with the QM forces from Gaussian. We summarize PUPIL architecture and implementation aspects, report efficiency and overhead measures, and discuss the computed results. ^1J. Torras, E. Deumens and S.B. Trickey, J. Computer Aided Mat. Des. 13, 201 (2006); J. Torras et al. Comp. Phys. Comm. 2006 [accepted

  13. Integrative NMR for biomolecular research.

    PubMed

    Lee, Woonghee; Cornilescu, Gabriel; Dashti, Hesam; Eghbalnia, Hamid R; Tonelli, Marco; Westler, William M; Butcher, Samuel E; Henzler-Wildman, Katherine A; Markley, John L

    2016-04-01

    NMR spectroscopy is a powerful technique for determining structural and functional features of biomolecules in physiological solution as well as for observing their intermolecular interactions in real-time. However, complex steps associated with its practice have made the approach daunting for non-specialists. We introduce an NMR platform that makes biomolecular NMR spectroscopy much more accessible by integrating tools, databases, web services, and video tutorials that can be launched by simple installation of NMRFAM software packages or using a cross-platform virtual machine that can be run on any standard laptop or desktop computer. The software package can be downloaded freely from the NMRFAM software download page ( http://pine.nmrfam.wisc.edu/download_packages.html ), and detailed instructions are available from the Integrative NMR Video Tutorial page ( http://pine.nmrfam.wisc.edu/integrative.html ). PMID:27023095

  14. Exploring biomolecular systems: From methodology to application

    NASA Astrophysics Data System (ADS)

    Liu, Pu

    This thesis describes new methodology development and applications in the computer simulation on biomolecular systems. To reduce the number of parallel processors in replica exchange, we deform the Hamiltonian function for each replica in such a way that the acceptance probability for the exchange of replica configurations does not depend on the number of explicit water molecules in the system. To accelerate barrier crossing in sampling of rough energy landscape, we invoke quantum tunnelling by using Feynman path-integral theory. Combined with local minimization, this new global optimization method successfully locates almost all the known classical global energy minima for Lennard-Jones clusters of size up to 100. We present a new methodology for calculating diffusion coefficients for molecules in confined space and apply it in water-vapor interface. We examine hydrogen bond dynamics of water-vapor interface and compare dynamics in polarizable and fixed charge water models. The result highlights the potential importance of polarization effect in the water-vapor interface. Finally, we discover a strong water drying transition in a biological protein system, the melittin tetramer. This is the first observation of such a strong transition in computer simulation for protein systems. The surface topology is shown to be very important for this drying transition.

  15. Microbial Cretaceous park: biodiversity of microbial fossils entrapped in amber

    NASA Astrophysics Data System (ADS)

    Martín-González, Ana; Wierzchos, Jacek; Gutiérrez, Juan C.; Alonso, Jesús; Ascaso, Carmen

    2009-05-01

    Microorganisms are the most ancient cells on this planet and they include key phyla for understanding cell evolution and Earth history, but, unfortunately, their microbial records are scarce. Here, we present a critical review of fossilized prokaryotic and eukaryotic microorganisms entrapped in Cretaceous ambers (but not exclusively from this geological period) obtained from deposits worldwide. Microbiota in ambers are rather diverse and include bacteria, fungi, and protists. We comment on the most important microbial records from the last 25 years, although it is not an exhaustive bibliographic compilation. The most frequently reported eukaryotic microfossils are shells of amoebae and protists with a cell wall or a complex cortex. Likewise, diverse dormant stages (palmeloid forms, resting cysts, spores, etc.) are abundant in ambers. Besides, viral and protist pathogens have been identified inside insects entrapped in amber. The situation regarding filamentous bacteria and fungi is quite confusing because in some cases, the same record was identified consecutively as a member of these phylogenetically distant groups. To avoid these identification errors in the future, we propose to apply a more resolute microscopic and analytical method in amber studies. Also, we discuss the most recent findings about ancient DNA repair and bacterial survival in remote substrates, which support the real possibility of ancient DNA amplification and bacterial resuscitation from Cretaceous resins.

  16. Solution influence on biomolecular equilibria - Nucleic acid base associations

    NASA Technical Reports Server (NTRS)

    Pohorille, A.; Pratt, L. R.; Burt, S. K.; Macelroy, R. D.

    1984-01-01

    Various attempts to construct an understanding of the influence of solution environment on biomolecular equilibria at the molecular level using computer simulation are discussed. First, the application of the formal statistical thermodynamic program for investigating biomolecular equilibria in solution is presented, addressing modeling and conceptual simplications such as perturbative methods, long-range interaction approximations, surface thermodynamics, and hydration shell. Then, Monte Carlo calculations on the associations of nucleic acid bases in both polar and nonpolar solvents such as water and carbon tetrachloride are carried out. The solvent contribution to the enthalpy of base association is positive (destabilizing) in both polar and nonpolar solvents while negative enthalpies for stacked complexes are obtained only when the solute-solute in vacuo energy is added to the total energy. The release upon association of solvent molecules from the first hydration layer around a solute to the bulk is accompanied by an increase in solute-solvent energy and decrease in solvent-solvent energy. The techniques presented are expectd to displace less molecular and more heuristic modeling of biomolecular equilibria in solution.

  17. [Advances in biomolecular machine: methane monooxygenases].

    PubMed

    Lu, Jixue; Wang, Shizhen; Fang, Baishan

    2015-07-01

    Methane monooxygenases (MMO), regarded as "an amazing biomolecular machine", catalyze the oxidation of methane to methanol under aerobic conditions. MMO catalyze the oxidation of methane elaborately, which is a novel way to catalyze methane to methanol. Furthermore, MMO can inspire the biomolecular machine design. In this review, we introduced MMO including structure, gene and catalytic mechanism. The history and the taxonomy of MMO were also introduced. PMID:26647577

  18. Impact Amber, Popcorn, and Pathology: The Biology of Impact Melt Breccias and Implications for Astrobiology

    NASA Astrophysics Data System (ADS)

    Harris, R. S.; Schultz, P. H.

    2007-03-01

    We present evidence that superheated impact melts can trap and preserve both floral and faunal remains forming "impact amber." We discuss terrestrial occurrences of impact amber and the strategy it suggests in searching for evidence of past life on other

  19. Two new fossil species of Cryptocephalus Geoffroy (Coleoptera: Chrysomelidae) from Baltic and Dominican Amber

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two new species of Cryptocephalus Geoffroy (Coleoptera: Chrysomelidae) are described and illustrated from fossil resin: Cryptocephalus groehni sp. nov (Baltic amber) and Cryptocephalus kheelorum sp. nov. (Dominican amber). These are the first described species of Cryptocephalinae from fossil resin. ...

  20. A new proposal concerning the botanical origin of Baltic amber

    PubMed Central

    Wolfe, Alexander P.; Tappert, Ralf; Muehlenbachs, Karlis; Boudreau, Marc; McKellar, Ryan C.; Basinger, James F.; Garrett, Amber

    2009-01-01

    Baltic amber constitutes the largest known deposit of fossil plant resin and the richest repository of fossil insects of any age. Despite a remarkable legacy of archaeological, geochemical and palaeobiological investigation, the botanical origin of this exceptional resource remains controversial. Here, we use taxonomically explicit applications of solid-state Fourier-transform infrared (FTIR) microspectroscopy, coupled with multivariate clustering and palaeobotanical observations, to propose that conifers of the family Sciadopityaceae, closely allied to the sole extant representative, Sciadopitys verticillata, were involved in the genesis of Baltic amber. The fidelity of FTIR-based chemotaxonomic inferences is upheld by modern–fossil comparisons of resins from additional conifer families and genera (Cupressaceae: Metasequoia; Pinaceae: Pinus and Pseudolarix). Our conclusions challenge hypotheses advocating members of either of the families Araucariaceae or Pinaceae as the primary amber-producing trees and correlate favourably with the progressive demise of subtropical forest biomes from northern Europe as palaeotemperatures cooled following the Eocene climate optimum. PMID:19570786

  1. IOT Overview: Calibrations of the VLTI Instruments (MIDI and AMBER)

    NASA Astrophysics Data System (ADS)

    Morel, S.; Rantakyrö, F.; Rivinius, T.; Stefl, S.; Hummel, C.; Brillant, S.; Schöller, M.; Percheron, I.; Wittkowski, M.; Richichi, A.; Ballester, P.

    We present here a short review of the calibration processes that are currently applied to the instruments AMBER and MIDI of the VLTI (Very Large Telescope Interferometer) at Paranal. We first introduce the general principles to calibrate the raw data (the "visibilities") that have been measured by long-baseline optical interferometry. Then, we focus on the specific case of the scientific operation of the VLTI instruments. We explain the criteria that have been used to select calibrator stars for the observations with the VLTI instruments, as well as the routine internal calibration techniques. Among these techniques, the "P2VM" (Pixel-to-Visibility Matrix) in the case of AMBER is explained. Also, the daily monitoring of AMBER and MIDI, that has recently been implemented, is shortly introduced.

  2. Isolation and Genetic Analysis of Amber uvrA and uvrB Mutants

    PubMed Central

    Morimyo, Mitsuoki; Shimazu, Yoshie; Ishii, Naoaki

    1976-01-01

    Genetic properties of amber uvrA and uvrB mutants of Escherichia coli K-12 are described. The isolation of three amber uvrA and two amber uvrB mutants indicates that the products of these genes are proteins. PMID:770438

  3. Adaptive Skin Meshes Coarsening for Biomolecular Simulation.

    PubMed

    Shi, Xinwei; Koehl, Patrice

    2011-06-01

    In this paper, we present efficient algorithms for generating hierarchical molecular skin meshes with decreasing size and guaranteed quality. Our algorithms generate a sequence of coarse meshes for both the surfaces and the bounded volumes. Each coarser surface mesh is adaptive to the surface curvature and maintains the topology of the skin surface with guaranteed mesh quality. The corresponding tetrahedral mesh is conforming to the interface surface mesh and contains high quality tetrahedral that decompose both the interior of the molecule and the surrounding region (enclosed in a sphere). Our hierarchical tetrahedral meshes have a number of advantages that will facilitate fast and accurate multigrid PDE solvers. Firstly, the quality of both the surface triangulations and tetrahedral meshes is guaranteed. Secondly, the interface in the tetrahedral mesh is an accurate approximation of the molecular boundary. In particular, all the boundary points lie on the skin surface. Thirdly, our meshes are Delaunay meshes. Finally, the meshes are adaptive to the geometry. PMID:21779137

  4. Adaptive Skin Meshes Coarsening for Biomolecular Simulation

    PubMed Central

    Shi, Xinwei; Koehl, Patrice

    2011-01-01

    In this paper, we present efficient algorithms for generating hierarchical molecular skin meshes with decreasing size and guaranteed quality. Our algorithms generate a sequence of coarse meshes for both the surfaces and the bounded volumes. Each coarser surface mesh is adaptive to the surface curvature and maintains the topology of the skin surface with guaranteed mesh quality. The corresponding tetrahedral mesh is conforming to the interface surface mesh and contains high quality tetrahedral that decompose both the interior of the molecule and the surrounding region (enclosed in a sphere). Our hierarchical tetrahedral meshes have a number of advantages that will facilitate fast and accurate multigrid PDE solvers. Firstly, the quality of both the surface triangulations and tetrahedral meshes is guaranteed. Secondly, the interface in the tetrahedral mesh is an accurate approximation of the molecular boundary. In particular, all the boundary points lie on the skin surface. Thirdly, our meshes are Delaunay meshes. Finally, the meshes are adaptive to the geometry. PMID:21779137

  5. Multidimensional persistence in biomolecular data

    PubMed Central

    Xia, Kelin; Wei, Guo-Wei

    2015-01-01

    Persistent homology has emerged as a popular technique for the topological simplification of big data, including biomolecular data. Multidimensional persistence bears considerable promise to bridge the gap between geometry and topology. However, its practical and robust construction has been a challenge. We introduce two families of multidimensional persistence, namely pseudo-multidimensional persistence and multiscale multidimensional persistence. The former is generated via the repeated applications of persistent homology filtration to high dimensional data, such as results from molecular dynamics or partial differential equations. The latter is constructed via isotropic and anisotropic scales that create new simiplicial complexes and associated topological spaces. The utility, robustness and efficiency of the proposed topological methods are demonstrated via protein folding, protein flexibility analysis, the topological denoising of cryo-electron microscopy data, and the scale dependence of nano particles. Topological transition between partial folded and unfolded proteins has been observed in multidimensional persistence. The separation between noise topological signatures and molecular topological fingerprints is achieved by the Laplace-Beltrami flow. The multiscale multidimensional persistent homology reveals relative local features in Betti-0 invariants and the relatively global characteristics of Betti-1 and Betti-2 invariants. PMID:26032339

  6. Multidimensional persistence in biomolecular data.

    PubMed

    Xia, Kelin; Wei, Guo-Wei

    2015-07-30

    Persistent homology has emerged as a popular technique for the topological simplification of big data, including biomolecular data. Multidimensional persistence bears considerable promise to bridge the gap between geometry and topology. However, its practical and robust construction has been a challenge. We introduce two families of multidimensional persistence, namely pseudomultidimensional persistence and multiscale multidimensional persistence. The former is generated via the repeated applications of persistent homology filtration to high-dimensional data, such as results from molecular dynamics or partial differential equations. The latter is constructed via isotropic and anisotropic scales that create new simiplicial complexes and associated topological spaces. The utility, robustness, and efficiency of the proposed topological methods are demonstrated via protein folding, protein flexibility analysis, the topological denoising of cryoelectron microscopy data, and the scale dependence of nanoparticles. Topological transition between partial folded and unfolded proteins has been observed in multidimensional persistence. The separation between noise topological signatures and molecular topological fingerprints is achieved by the Laplace-Beltrami flow. The multiscale multidimensional persistent homology reveals relative local features in Betti-0 invariants and the relatively global characteristics of Betti-1 and Betti-2 invariants. PMID:26032339

  7. The Amber ff99 Force Field Predicts Relative Free Energy Changes for RNA Helix Formation

    PubMed Central

    Spasic, Aleksandar; Serafini, John; Mathews, David H.

    2012-01-01

    The ability of the Amber ff99 force field to predict relative free energies of RNA helix formation was investigated. The test systems were three hexaloop RNA hairpins with identical loops and varying stems. The potential of mean force of stretching the hairpins from the native state to an extended conformation was calculated with umbrella sampling. Because the hairpins have identical loop sequence, the differences in free energy changes are only from the stem composition. The Amber ff99 force field was able to correctly predict the order of stabilities of the hairpins, although the magnitude of the free energy change is larger than that determined by optical melting experiments. The two measurements cannot be compared directly because the unfolded state in the optical melting experiments is a random coil, while the end state in the umbrella sampling simulations was an elongated chain. The calculations can be compared to reference data by using a thermodynamic cycle. By applying the thermodynamic cycle to the transitions between the hairpins using simulations and nearest neighbor data, agreement was found to be within the sampling error of simulations, thus demonstrating that ff99 force field is able to accurately predict relative free energies of RNA helix formation. PMID:23112748

  8. Fragment-based error estimation in biomolecular modeling

    PubMed Central

    Faver, John C.; Merz, Kenneth M.

    2013-01-01

    Computer simulations are becoming an increasingly more important component of drug discovery. Computational models are now often able to reproduce and sometimes even predict outcomes of experiments. Still, potential energy models such as force fields contain significant amounts of bias and imprecision. We have shown how even small uncertainties in potential energy models can propagate to yield large errors, and have devised some general error-handling protocols for biomolecular modeling with imprecise energy functions. Herein we discuss those protocols within the contexts of protein–ligand binding and protein folding. PMID:23993915

  9. New fossil ants in French Cretaceous amber (Hymenoptera: Formicidae)

    NASA Astrophysics Data System (ADS)

    Perrichot, Vincent; Nel, André; Néraudeau, Didier; Lacau, Sébastien; Guyot, Thierry

    2008-02-01

    Recent studies on the ant phylogeny are mainly based on the molecular analyses of extant subfamilies and do not include the extinct, only Cretaceous subfamily Sphecomyrminae. However, the latter is of major importance for ant relationships, as it is considered the most basal subfamily. Therefore, each new discovery of a Mesozoic ant is of high interest for improving our understanding of their early history and basal relationships. In this paper, a new sphecomyrmine ant, allied to the Burmese amber genus Haidomyrmex, is described from mid-Cretaceous amber of France as Haidomyrmodes mammuthus gen. and sp. n. The diagnosis of the tribe Haidomyrmecini is emended based on the new type material, which includes a gyne (alate female) and two incomplete workers. The genus Sphecomyrmodes, hitherto known by a single species from Burmese amber, is also reported and a new species described as S. occidentalis sp. n. after two workers remarkably preserved in a single piece of Early Cenomanian French amber. The new fossils provide additional information on early ant diversity and relationships and demonstrate that the monophyly of the Sphecomyrminae, as currently defined, is still weakly supported.

  10. Structural changes in amber due to uranium mineralization.

    PubMed

    Havelcová, Martina; Machovič, Vladimír; Mizera, Jiří; Sýkorová, Ivana; René, Miloš; Borecká, Lenka; Lapčák, Ladislav; Bičáková, Olga; Janeček, Oldřich; Dvořák, Zdeněk

    2016-07-01

    The presence of uranium, with a bulk mass fraction of about 1.5 wt% and radiolytic alterations are a feature of Cenomanian amber from Křižany, at the northeastern edge of the North Bohemian Cretaceous uranium ore district. Pores and microcracks in the amber were filled with a mineral admixture, mainly in the form of Zr-Y-REE enriched uraninite. As a result of radiolytic alterations due to the presence of uranium, structural changes were observed in the Křižany amber in comparison with a reference amber from Nové Strašecí in central Bohemia; this was of similar age and botanical origin but did not contain elevated levels of uranium. Structural changes involved an increase in aromaticity due to dehydroaromatization of aliphatic cyclic hydrocarbons, loss of oxygen functional groups, an increase in the degree of polymerization, crosslinking of CC bonds, formation of a three-dimensional hydrocarbon network in the bulk organic matrix, and carbonization of the organic matrix around the uraninite infill. PMID:27085038

  11. Bird's nest fungi (Nidulariales: Nidulariaceae) in Baltic and Dominican amber.

    PubMed

    Poinar, George

    2014-03-01

    Nidula baltica sp. nov. and Cyathus dominicanus sp. nov. are described from Cenozoic Baltic and Dominican amber. These are the first fossil members of the Family Nidulariaceae and show that the basic characteristics of this group were already established some 40-50 million years ago. PMID:24607356

  12. Symmetrization of the AMBER and CHARMM force fields.

    PubMed

    Małolepsza, Edyta; Strodel, Birgit; Khalili, Mey; Trygubenko, Semen; Fejer, Szilard N; Wales, David J

    2010-05-01

    The AMBER and CHARMM force fields are analyzed from the viewpoint of the permutational symmetry of the potential for feasible exchanges of identical atoms and chemical groups in amino and nucleic acids. In each case, we propose schemes for symmetrizing the potentials, which greatly facilitate the bookkeeping associated with constructing kinetic transition networks via geometry optimization. PMID:20082393

  13. Structural Survey of Zinc Containing Proteins and the Development of the Zinc AMBER Force Field (ZAFF)

    PubMed Central

    Peters, Martin B.; Yang, Yue; Wang, Bing; Füsti-Molnár, László; Weaver, Michael N.; Merz, Kenneth M.

    2010-01-01

    Currently the Protein Data Bank (PDB) contains over 18,000 structures that contain a metal ion including Na, Mg, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Pd, Ag, Cd, Ir, Pt, Au, and Hg. In general, carrying out classical molecular dynamics (MD) simulations of metalloproteins is a convoluted and time consuming process. Herein, we describe MCPB (Metal Center Parameter Builder), which allows one, to conveniently and rapidly incorporate metal ions using the bonded plus electrostatics model (Hoops et al., J. Am. Chem. Soc. 1991, 113, 8262–8270) into the AMBER Force Field (FF). MCPB was used to develop a Zinc FF, ZAFF, which is compatible with the existing AMBER FFs. The PDB was mined for all Zn containing structures with most being tetrahedrally bound. The most abundant primary shell ligand combinations were extracted and FFs were created. These include Zn bound to CCCC, CCCH, CCHH, CHHH, HHHH, HHHO, HHOO, HOOO, HHHD, and HHDD (O = water and the remaining are 1 letter amino acid codes). Bond and angle force constants and RESP charges were obtained from B3LYP/6-31G* calculations of model structures from the various primary shell combinations. MCPB and ZAFF can be used to create FFs for MD simulations of metalloproteins to study enzyme catalysis, drug design and metalloprotein crystal refinement. PMID:20856692

  14. Perspective: Markov models for long-timescale biomolecular dynamics

    SciTech Connect

    Schwantes, C. R.; McGibbon, R. T.; Pande, V. S.

    2014-09-07

    Molecular dynamics simulations have the potential to provide atomic-level detail and insight to important questions in chemical physics that cannot be observed in typical experiments. However, simply generating a long trajectory is insufficient, as researchers must be able to transform the data in a simulation trajectory into specific scientific insights. Although this analysis step has often been taken for granted, it deserves further attention as large-scale simulations become increasingly routine. In this perspective, we discuss the application of Markov models to the analysis of large-scale biomolecular simulations. We draw attention to recent improvements in the construction of these models as well as several important open issues. In addition, we highlight recent theoretical advances that pave the way for a new generation of models of molecular kinetics.

  15. Molecular Dynamics Simulations of 441 Two-Residue Peptides in Aqueous Solution: Conformational Preferences and Neighboring Residue Effects with the Amber ff99SB-ildn-nmr Force Field

    PubMed Central

    Li, Shuxiang; Andrews, Casey T.; Frembgen-Kesner, Tamara; Miller, Mark S.; Siemonsma, Stephen L.; Collingsworth, Timothy D.; Rockafellow, Isaac T.; Ngo, Nguyet Anh; Campbell, Brady A.; Brown, Reid F.; Guo, Chengxuan; Schrodt, Michael; Liu, Yu-Tsan; Elcock, Adrian H.

    2015-01-01

    Understanding the intrinsic conformational preferences of amino acids and the extent to which they are modulated by neighboring residues is a key issue for developing predictive models of protein folding and stability. Here we present the results of 441 independent explicit-solvent MD simulations of all possible two-residue peptides that contain the 20 standard amino acids with histidine modeled in both its neutral and protonated states. 3Jhnhα coupling constants and δhα chemical shifts calculated from the MD simulations correlate quite well with recently published experimental measurements for a corresponding set of two-residue peptides. Neighboring residue effects (NREs) on the average 3Jhnhα and δhα values of adjacent residues are also reasonably well reproduced, with the large NREs exerted experimentally by aromatic residues, in particular, being accurately captured. NREs on the secondary structure preferences of adjacent amino acids have been computed and compared with corresponding effects observed in a coil library and the average β-turn preferences of all amino acid types have been determined. Finally, the intrinsic conformational preferences of histidine, and its NREs on the conformational preferences of adjacent residues, are both shown to be strongly affected by the protonation state of the imidazole ring. PMID:26579777

  16. A Validation Study of the General Amber Force Field Applied to Energetic Molecular Crystals

    NASA Astrophysics Data System (ADS)

    Bergh, Magnus; Caleman, Carl

    2016-01-01

    Molecula dynamics is a well-established tool to computationally study molecules. However, to reach predictive capability at the level required for applied research and design, extensive validation of the available force fields is pertinent. Here we present a study of density, isothermal compressibility and coefficients of thermal expansion of four energetic materials (FOX-7, RDX, CL-20 and HMX) based on molecular dynamics simulations with the General Amber Force Field (GAFF), and compare the results to experimental measurements from the literature. Furthermore, we quantify the accuracy of the calculated properties through hydrocode simulation of a typical impact scenario. We find that molecular dynamics simulations with generic and computationally efficient force fields may be used to understand and estimate important physical properties of nitramine-like energetic materials.

  17. VIBE: A virtual biomolecular environment for interactive molecular modeling

    SciTech Connect

    Cruz-Neira, C.; Langley, R.; Bash, P.A.

    1996-12-31

    Virtual reality tightly coupled to high performance computing and communications ushers in a new era for the study of molecular recognition and the rational design of pharmaceutical compounds. We have created a Virtual Biomolecular Environment (VIBE), which consists of (1) massively parallel computing to simulate the physical and chemical properties of a molecular system, (2) the Cave Automatic Virtual Environment (CAVE) for immersive display and interaction with the molecular system, and (3) a high-speed network interface to exchange data between the simulation and the CAVE. VIBE enables molecular scientists to have a visual, auditory, and haptic experience with a chemical system, while simultaneously manipulating its physical properties by steering, in real-time, a simulation executed on a supercomputer. We demonstrate the characteristics of VIBE using an HIV protease-cyclic urea inhibitor complex. 22 refs., 4 figs.

  18. 40Ar/39Ar systematics and argon diffusion in amber: implications for ancient earth atmospheres

    USGS Publications Warehouse

    Landis, G.P.; Snee, L.W.

    1991-01-01

    Argon isotope data indicate retained argon in bulk amber (matrix gas) is radiogenic [40Ar/39Ar ???32o] than the much more abundant surface absorbed argon [40Ar/39Ar ???295.5]. Neutron-induced 39Ar is retained in amber during heating experiments to 150?? -250??C, with no evidence of recoiled 39Ar found after irradiation. A maximum permissible volume diffusion coefficient of argon in amber (at ambient temperature) D???1.5 x 10-17 cm2S-1 is calculated from 39Ar retention. 40Ar/39Ar age calculations indicate Dominican Republic amber is ??? 45 Ma and North Dakota amber is ??? 89 Ma, both at least reasonable ages for the amber based upon stratigraphic and paleontological constraints and upon the small amount of radiogenic 40Ar. To date, over 300 gas analyses of ambers and resins of Cretaceous to Recent age that are geographically distributed among fifteen noted world locations identify mixtures of gases in different sites within amber (Berner and Landis, 1988). The presence of multiple mixing trends between compositionally distinct end-members gases within the same sample and evidence for retained radiogenic argon within the amber argue persuasivley against rapid exchange by diffusion of amber-contained gases with moder air. Only gas in primary bubbles entrapped between successive flows of tree resin has been interpreted as original "ancient air", which is an O2-rich end-member gas with air-like N2/Ar ratios. Gas analyses of these primary bubbles indicate atmospheric O2 levels in the Late Cretaceous of ??? 35%, and that atmospheric O2 dropped by early Tertiary time to near a present atmospheric level of 21% O2. A very low argon diffusion coefficient in amber persuasively argues for a gas in primary bubbles trapped in amber being ancient air (possibly modified only by O2 reaction with amber). ?? 1991.

  19. Mummified precocial bird wings in mid-Cretaceous Burmese amber

    PubMed Central

    Xing, Lida; McKellar, Ryan C.; Wang, Min; Bai, Ming; O'Connor, Jingmai K.; Benton, Michael J.; Zhang, Jianping; Wang, Yan; Tseng, Kuowei; Lockley, Martin G.; Li, Gang; Zhang, Weiwei; Xu, Xing

    2016-01-01

    Our knowledge of Cretaceous plumage is limited by the fossil record itself: compression fossils surrounding skeletons lack the finest morphological details and seldom preserve visible traces of colour, while discoveries in amber have been disassociated from their source animals. Here we report the osteology, plumage and pterylosis of two exceptionally preserved theropod wings from Burmese amber, with vestiges of soft tissues. The extremely small size and osteological development of the wings, combined with their digit proportions, strongly suggests that the remains represent precocial hatchlings of enantiornithine birds. These specimens demonstrate that the plumage types associated with modern birds were present within single individuals of Enantiornithes by the Cenomanian (99 million years ago), providing insights into plumage arrangement and microstructure alongside immature skeletal remains. This finding brings new detail to our understanding of infrequently preserved juveniles, including the first concrete examples of follicles, feather tracts and apteria in Cretaceous avialans. PMID:27352215

  20. Mummified precocial bird wings in mid-Cretaceous Burmese amber.

    PubMed

    Xing, Lida; McKellar, Ryan C; Wang, Min; Bai, Ming; O'Connor, Jingmai K; Benton, Michael J; Zhang, Jianping; Wang, Yan; Tseng, Kuowei; Lockley, Martin G; Li, Gang; Zhang, Weiwei; Xu, Xing

    2016-01-01

    Our knowledge of Cretaceous plumage is limited by the fossil record itself: compression fossils surrounding skeletons lack the finest morphological details and seldom preserve visible traces of colour, while discoveries in amber have been disassociated from their source animals. Here we report the osteology, plumage and pterylosis of two exceptionally preserved theropod wings from Burmese amber, with vestiges of soft tissues. The extremely small size and osteological development of the wings, combined with their digit proportions, strongly suggests that the remains represent precocial hatchlings of enantiornithine birds. These specimens demonstrate that the plumage types associated with modern birds were present within single individuals of Enantiornithes by the Cenomanian (99 million years ago), providing insights into plumage arrangement and microstructure alongside immature skeletal remains. This finding brings new detail to our understanding of infrequently preserved juveniles, including the first concrete examples of follicles, feather tracts and apteria in Cretaceous avialans. PMID:27352215

  1. Double fossilization in eukaryotic microorganisms from Lower Cretaceous amber

    PubMed Central

    Martín-González, Ana; Wierzchos, Jacek; Gutiérrez, Juan-Carlos; Alonso, Jesús; Ascaso, Carmen

    2009-01-01

    Background Microfossils are not only useful for elucidating biological macro- and microevolution but also the biogeochemical history of our planet. Pyritization is the most important and extensive mode of preservation of animals and especially of plants. Entrapping in amber, a fossilized resin, is considered an alternative mode of biological preservation. For the first time, the internal organization of 114-million-year-old microfossils entrapped in Lower Cretaceous amber is described and analyzed, using adapted scanning electron microscopy in backscattered electron mode in association with energy dispersive X-ray spectroscopy microanalysis. Double fossilization of several protists included in diverse taxonomical groups and some vegetal debris is described and analyzed. Results In protists without an exoskeleton or shell (ciliates, naked amoebae, flagellates), determinate structures, including the nuclei, surface envelopes (cortex or cytoplasmic membrane) and hyaloplasm are the main sites of pyritization. In protists with a biomineralized skeleton (diatoms), silicon was replaced by pyrite. Permineralization was the main mode of pyritization. Framboidal, subhedral and microcrystalline are the predominant pyrite textures detected in the cells. Abundant pyritized vegetal debris have also been found inside the amber nuggets and the surrounding sediments. This vegetal debris usually contained numerous pyrite framboids and very densely packed polycrystalline pyrite formations infilled with different elements of the secondary xylem. Conclusion Embedding in amber and pyritization are not always alternative modes of biological preservation during geological times, but double fossilization is possible under certain environmental conditions. Pyritization in protists shows a quite different pattern with regard to plants, due to the different composition and cellular architecture in these microorganisms and organisms. Anaerobic sulphate-reducing bacteria could play a crucial

  2. Diversity of Scydmaeninae (Coleoptera: Staphylinidae) in Upper Eocene Rovno amber.

    PubMed

    Jałoszyński, Paweł; Perkovsky, Evgeny

    2016-01-01

    Among nearly 1270 inclusions of Coleoptera found in Upper Eocene Rovno amber, 69 were identified as ant-like stone beetles (Scydmaeninae); 34 were possible to unambiguously determine to the tribal level and were studied in detail. Rovnoleptochromus ableptonoides gen. & sp. n. (Mastigitae: Clidicini), Vertheia quadrisetosa gen. & sp. n. (Cephenniitae: Eutheiini), Cephennomicrus giganteus sp. n. (Cephenniitae: Cephenniini), Glaesoconnus unicus gen. & sp. n. (Scydmaenitae: Glandulariini), Rovnoscydmus frontalis gen. & sp. n. (Scydmaenitae: Glandulariini; type species of Rovnoscydmus), Rovnoscydmus microscopicus sp. n., Euconnus (incertae sedis, near Cladoconnus) palaeogenus sp. n. (Scydmaenitae: Glandulariini), and Stenichnus (s. str.) proavus sp. n. (Scydmaenitae: Glandulariini) are described. Additionally, specimens representing one undescribed species of Vertheia, one of Cephennodes, five of Cephennomicrus, one of Euconnus, one of Microscydmus are recorded, and nine specimens representing an unknown number of species of Rovnoscydmus (and two putative Rovnoscydmus), one Euconnus (and one putative Euconnus), two putative Microscydmus and one putative Scydmoraphes were found in the studied material. The composition of Scydmaeninae fauna in Rovno amber is discussed in the context of ecological preferences and distribution of extant taxa. It is concluded that subtropical and tropical taxa were present in the region where Rovno amber has formed, most notably the second genus and species of the extant tribe Clidicini known from the Eocene of Europe, and six species of the extant genus Cephennomicrus, for the first time found in the fossil record. An annotated catalog of nominal species of Scydmaeninae known in the fossil record is given. PMID:27615867

  3. New fossil Stylops (Strepsiptera: Stylopidae) from Dominican amber.

    PubMed

    Kogan, Marcos; Poinar, George

    2010-01-01

    Description of a new species of the genus Stylops from Dominican amber expands the number of families of this order represented by fossils of the mid-Eocene in the Neotropical region. The specimen described herein is reasonably well preserved, except for the tip of the abdomen that hampered observation of the aedeagus. The specimen fits definition of the comtemporary genus Stylops and differs from a related species, Jantarostylops kinzelbachi Kulicka, from Baltic amber, by the larger number of ommatidia, relative proportion of antennal segments, and venation of hind wings. The specimen differs from other contemporary species of Nearctic Stylops in, among other characters, the smaller size, sub-costa detached from costa and maxillary structure. Discovery of this fossil species of Stylops provides evidence of a possibly more temperate climate in the Antilles, since most contemporary species of the genus occur predominantly in the temperate zones of the Nearctic, Palearctic, and Oriental regions. All known species of the genus parasitize bees of the genus Andrena ( sensu lato). Existence of a fossil andrenid, Protandrena eickworti Rozen Jr, of the same Dominican amber, offers evidence of a potential host for this new species of Stylops. PMID:20498960

  4. Seeking carotenoid pigments in amber-preserved fossil feathers

    PubMed Central

    Thomas, Daniel B.; Nascimbene, Paul C.; Dove, Carla J.; Grimaldi, David A.; James, Helen F.

    2014-01-01

    Plumage colours bestowed by carotenoid pigments can be important for visual communication and likely have a long evolutionary history within Aves. Discovering plumage carotenoids in fossil feathers could provide insight into the ecology of ancient birds and non-avian dinosaurs. With reference to a modern feather, we sought chemical evidence of carotenoids in six feathers preserved in amber (Miocene to mid-Cretaceous) and in a feather preserved as a compression fossil (Eocene). Evidence of melanin pigmentation and microstructure preservation was evaluated with scanning electron and light microscopies. We observed fine microstructural details including evidence for melanin pigmentation in the amber and compression fossils, but Raman spectral bands did not confirm the presence of carotenoids in them. Carotenoids may have been originally absent from these feathers or the pigments may have degraded during burial; the preservation of microstructure may suggest the former. Significantly, we show that carotenoid plumage pigments can be detected without sample destruction through an amber matrix using confocal Raman spectroscopy. PMID:24909554

  5. Seeking carotenoid pigments in amber-preserved fossil feathers

    NASA Astrophysics Data System (ADS)

    Thomas, Daniel B.; Nascimbene, Paul C.; Dove, Carla J.; Grimaldi, David A.; James, Helen F.

    2014-06-01

    Plumage colours bestowed by carotenoid pigments can be important for visual communication and likely have a long evolutionary history within Aves. Discovering plumage carotenoids in fossil feathers could provide insight into the ecology of ancient birds and non-avian dinosaurs. With reference to a modern feather, we sought chemical evidence of carotenoids in six feathers preserved in amber (Miocene to mid-Cretaceous) and in a feather preserved as a compression fossil (Eocene). Evidence of melanin pigmentation and microstructure preservation was evaluated with scanning electron and light microscopies. We observed fine microstructural details including evidence for melanin pigmentation in the amber and compression fossils, but Raman spectral bands did not confirm the presence of carotenoids in them. Carotenoids may have been originally absent from these feathers or the pigments may have degraded during burial; the preservation of microstructure may suggest the former. Significantly, we show that carotenoid plumage pigments can be detected without sample destruction through an amber matrix using confocal Raman spectroscopy.

  6. Conformational dynamics of two natively unfolded fragment peptides: Comparison of the AMBER and CHARMM force fields

    PubMed Central

    Chen, Wei; Shi, Chuanyin; MacKerell, Alexander D.; Shen, Jana

    2015-01-01

    Physics-based force fields are the backbone of molecular dynamics simulations. In recent years, significant progress has been made in the assessment and improvement of commonly-used force fields for describing conformational dynamics of folded proteins. However, the accuracy for the unfolded states remains unclear. The latter is however important for detailed studies of protein folding pathways, conformational transitions involving unfolded states and dynamics of intrinsically disordered proteins. In this work we compare the three commonly-used force fields, AMBER ff99SB-ILDN, CHARMM22/CMAP and CHARMM36, for modeling the natively unfolded fragment peptides, NTL9(1-22) and NTL9(6-17), using explicit-solvent replica-exchange molecular dynamics simulations. All three simulations show that NTL9(6-17) is completely unstructured, while NTL9(1-22) transiently samples various β-hairpin states, reminiscent of the first β-hairpin in the structure of the intact NT9 protein. The radius of gyration of the two peptides is force field independent but likely underestimated due to the current deficiency of additive force fields. Compared to the CHARMM force fields, ff99SB-ILDN gives slightly higher β-sheet propensity and more native-like residual structures for NTL9(1-22), which may be attributed to its known β preference. Surprisingly, only two sequence-local pairs of charged residues make appreciable ionic contacts in the simulations of NTL9(1-22), which are sampled slightly more by the CHARMM force fields. Taken together, these data suggest that the current CHARMM and AMBER force fields are globally in agreement in modeling the unfolded states corresponding to β-sheet in the folded structure, while differing in details such as the native-likeness of the residual structures and interactions. PMID:26020564

  7. Conformational Dynamics of Two Natively Unfolded Fragment Peptides: Comparison of the AMBER and CHARMM Force Fields.

    PubMed

    Chen, Wei; Shi, Chuanyin; MacKerell, Alexander D; Shen, Jana

    2015-06-25

    Physics-based force fields are the backbone of molecular dynamics simulations. In recent years, significant progress has been made in the assessment and improvement of commonly used force fields for describing conformational dynamics of folded proteins. However, the accuracy for the unfolded states remains unclear. The latter is however important for detailed studies of protein folding pathways, conformational transitions involving unfolded states, and dynamics of intrinsically disordered proteins. In this work, we compare the three commonly used force fields, AMBER ff99SB-ILDN, CHARMM22/CMAP, and CHARMM36, for modeling the natively unfolded fragment peptides, NTL9(1-22) and NTL9(6-17), using explicit-solvent replica-exchange molecular dynamics simulations. All three simulations show that NTL9(6-17) is completely unstructured, while NTL9(1-22) transiently samples various β-hairpin states, reminiscent of the first β-hairpin in the structure of the intact NTL9 protein. The radius of gyration of the two peptides is force field independent but likely underestimated due to the current deficiency of additive force fields. Compared to the CHARMM force fields, ff99SB-ILDN gives slightly higher β-sheet propensity and more native-like residual structures for NTL9(1-22), which may be attributed to its known β preference. Surprisingly, only two sequence-local pairs of charged residues make appreciable ionic contacts in the simulations of NTL9(1-22), which are sampled slightly more by the CHARMM force fields. Taken together, these data suggest that the current CHARMM and AMBER force fields are globally in agreement in modeling the unfolded states corresponding to β-sheet in the folded structure, while differing in details such as the native-likeness of the residual structures and interactions. PMID:26020564

  8. Amber bearing deposit in SW Saaremaa, Estonia - sedimentary environment and palaeogeography

    NASA Astrophysics Data System (ADS)

    Post, Triine; Ots, Mirja; Rosentau, Alar

    2015-04-01

    The paper describes a deposit of natural amber found form Estonia. Finds of natural amber are important in the context of the Bronze Age archaeology, because the amount of Bronze Age archaeological amber found in Estonia is very small. Most of the amber is from the Late Bronze Age and is mainly discovered from the fortified settlements in Saaremaa, some also from burials of the same time. Now, the discovery of the deposit of natural amber in the island of Saaremaa makes us reconsider the general opinion that all archaeological amber items found in Estonia have been imported. The aim of this study is to clarify the origin and age of the natural amber using scientific methods. A layer of buried organic matter (BOM) containing pieces of natural amber was discovered in Holocene coastal plain on Sõrve peninsula, island of Saaremaa. The BOM layer is buried under ca 90 cm-thick sandy coastal deposits and consists of remains of coastal plants and pieces of driftwood. Palaeogeographic reconstructions and sediment composition indicate that the layer was deposited in the coastal zone and buried quickly by sandy marine sediments. According to radiocarbon dating of the seeds of Polygonum lapathifolium the formation of the BOM layer remained in the Late Bronze Age (2480 ± 30 14C yr BP). Amber finds have been characterized using ATR-FTIR spectroscopy and isotope analysis of light elements (H and C) - both are referring to Baltic amber. Therefore it is probable that amber was transported to Saaremaa within organic matter from the Latvian-Lithuanian coastal zone where secondary Baltic amber deposits are widely known.

  9. Computational and theoretical aspects of biomolecular structure and dynamics

    SciTech Connect

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

    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.

  10. A statistical mechanical description of biomolecular hydration

    SciTech Connect

    1996-02-01

    We present an efficient and accurate theoretical description of the structural hydration of biological macromolecules. The hydration of molecules of almost arbitrary size (tRNA, antibody-antigen complexes, photosynthetic reaction centre) can be studied in solution and in the crystal environment. The biomolecular structure obtained from x-ray crystallography, NMR, or modeling is required as input information. The structural arrangement of water molecules near a biomolecular surface is represented by the local water density analogous to the corresponding electron density in an x-ray diffraction experiment. The water-density distribution is approximated in terms of two- and three-particle correlation functions of solute atoms with water using a potentials-of-mean-force expansion.

  11. General AMBER Force Field Parameters for Diphenyl Diselenides and Diphenyl Ditellurides.

    PubMed

    Torsello, Mauro; Pimenta, Antonio C; Wolters, Lando P; Moreira, Irina S; Orian, Laura; Polimeno, Antonino

    2016-06-30

    The General AMBER Force Field (GAFF) has been extended to describe a series of selenium and tellurium diphenyl dichalcogenides. These compounds, besides being eco-friendly catalysts for numerous oxidations in organic chemistry, display peroxidase activity, i.e., can reduce hydrogen peroxide and harmful organic hydroperoxides to water/alcohols and as such are very promising antioxidant drugs. The novel GAFF parameters are tested in MD simulations in different solvents and the (77)Se NMR chemical shift of diphenyl diselenide is computed using structures extracted from MD snapshots and found in nice agreement with the measured value in CDCl3. The whole computational protocol is described in detail and integrated with in-house code to allow easy derivation of the force field parameters for analogous compounds as well as for Se/Te organocompounds in general. PMID:27267296

  12. Solvation thermodynamic mapping of molecular surfaces in AmberTools: GIST.

    PubMed

    Ramsey, Steven; Nguyen, Crystal; Salomon-Ferrer, Romelia; Walker, Ross C; Gilson, Michael K; Kurtzman, Tom

    2016-08-01

    The expulsion of water from surfaces upon molecular recognition and nonspecific association makes a major contribution to the free energy changes of these processes. In order to facilitate the characterization of water structure and thermodynamics on surfaces, we have incorporated Grid Inhomogeneous Solvation Theory (GIST) into the CPPTRAJ toolset of AmberTools. GIST is a grid-based implementation of Inhomogeneous Fluid Solvation Theory, which analyzes the output from molecular dynamics simulations to map out solvation thermodynamic and structural properties on a high-resolution, three-dimensional grid. The CPPTRAJ implementation, called GIST-cpptraj, has a simple, easy-to-use command line interface, and is open source and freely distributed. We have also developed a set of open-source tools, called GISTPP, which facilitate the analysis of GIST output grids. Tutorials for both GIST-cpptraj and GISTPP can be found at ambermd.org. © 2016 Wiley Periodicals, Inc. PMID:27317094

  13. Refinement of the AMBER Force Field for Nucleic Acids: Improving the Description of α/γ Conformers

    PubMed Central

    Pérez, Alberto; Marchán, Iván; Svozil, Daniel; Sponer, Jiri; Cheatham, Thomas E.; Laughton, Charles A.; Orozco, Modesto

    2007-01-01

    We present here the parmbsc0 force field, a refinement of the AMBER parm99 force field, where emphasis has been made on the correct representation of the α/γ concerted rotation in nucleic acids (NAs). The modified force field corrects overpopulations of the α/γ = (g+,t) backbone that were seen in long (more than 10 ns) simulations with previous AMBER parameter sets (parm94-99). The force field has been derived by fitting to high-level quantum mechanical data and verified by comparison with very high-level quantum mechanical calculations and by a very extensive comparison between simulations and experimental data. The set of validation simulations includes two of the longest trajectories published to date for the DNA duplex (200 ns each) and the largest variety of NA structures studied to date (15 different NA families and 97 individual structures). The total simulation time used to validate the force field includes near 1 μs of state-of-the-art molecular dynamics simulations in aqueous solution. PMID:17351000

  14. Aligning Biomolecular Networks Using Modular Graph Kernels

    NASA Astrophysics Data System (ADS)

    Towfic, Fadi; Greenlee, M. Heather West; Honavar, Vasant

    Comparative analysis of biomolecular networks constructed using measurements from different conditions, tissues, and organisms offer a powerful approach to understanding the structure, function, dynamics, and evolution of complex biological systems. We explore a class of algorithms for aligning large biomolecular networks by breaking down such networks into subgraphs and computing the alignment of the networks based on the alignment of their subgraphs. The resulting subnetworks are compared using graph kernels as scoring functions. We provide implementations of the resulting algorithms as part of BiNA, an open source biomolecular network alignment toolkit. Our experiments using Drosophila melanogaster, Saccharomyces cerevisiae, Mus musculus and Homo sapiens protein-protein interaction networks extracted from the DIP repository of protein-protein interaction data demonstrate that the performance of the proposed algorithms (as measured by % GO term enrichment of subnetworks identified by the alignment) is competitive with some of the state-of-the-art algorithms for pair-wise alignment of large protein-protein interaction networks. Our results also show that the inter-species similarity scores computed based on graph kernels can be used to cluster the species into a species tree that is consistent with the known phylogenetic relationships among the species.

  15. Force fluctuations impact kinetics of biomolecular systems.

    PubMed

    Koslover, Elena F; Spakowitz, Andrew J

    2012-07-01

    A wide array of biological processes occur at rates that vary significantly with force. Instantaneous molecular forces fluctuate due to thermal noise and active processes, leading to concomitant fluctuations in biomolecular rate constants. We demonstrate that such fluctuations have a dramatic effect on the transition kinetics of force-dependent processes. As an illustrative, biologically relevant example, we model the pausing of eukaryotic RNA polymerase as it transcribes nucleosomal DNA. Incorporating force fluctuations in the model yields qualitatively different predictions for the pausing time scales when compared to behavior under the average force alone. We use our model to illustrate the broad range of behaviors that can arise in biomolecular processes that are susceptible to force fluctuations. The fluctuation time scale, which varies significantly for in vivo biomolecular processes, yields very different results for overall rates and dramatically alters the force regime of relevance to the transition. Our results emphasize the importance of transient high-force behavior for determining kinetics in the fluctuating environment of a living cell. PMID:23005451

  16. Force fluctuations impact kinetics of biomolecular systems

    NASA Astrophysics Data System (ADS)

    Koslover, Elena F.; Spakowitz, Andrew J.

    2012-07-01

    A wide array of biological processes occur at rates that vary significantly with force. Instantaneous molecular forces fluctuate due to thermal noise and active processes, leading to concomitant fluctuations in biomolecular rate constants. We demonstrate that such fluctuations have a dramatic effect on the transition kinetics of force-dependent processes. As an illustrative, biologically relevant example, we model the pausing of eukaryotic RNA polymerase as it transcribes nucleosomal DNA. Incorporating force fluctuations in the model yields qualitatively different predictions for the pausing time scales when compared to behavior under the average force alone. We use our model to illustrate the broad range of behaviors that can arise in biomolecular processes that are susceptible to force fluctuations. The fluctuation time scale, which varies significantly for in vivo biomolecular processes, yields very different results for overall rates and dramatically alters the force regime of relevance to the transition. Our results emphasize the importance of transient high-force behavior for determining kinetics in the fluctuating environment of a living cell.

  17. Photosynthesis biomolecular electronics, and renewable fuels production

    SciTech Connect

    Greenbaum, E.

    1995-12-31

    The term {open_quotes}biomolecular electronics{close_quotes} evokes two powerful images of 20th century science and technology. First, the {open_quotes}bio{close_quotes} prefix of {open_quotes}molecular{close_quotes} explicitly acknowledges the molecular basis and understanding of living state systems. It is this understanding that forms the foundation of molecular biology, immunology, and genetic engineering. Second, {open_quotes}electronics{close_quotes} in the context of technology is understood to be that of electronic devices, starting from vacuum tubes and progressing through transistors, integrated circuits, and the semiconductor electronics industry comprising communications and consumer electronics, as examples. The conflation of these two terms into {open_quotes}biomolecular electronics{close_quotes} implies a radical concept: the construction of practical electronic devices from biomolecular components. This presentation will focus on an understanding and interpretation of the molecular architecture of the photosynthetic membrane and its potential application for the construction of optoelectronic devices and the production of renewable hydrogen via photosynthetic water splitting. Recent advances on direct electrical contact of the electron transport chain of photosynthesis with metallocatalysts as well as the discovery of new photoreactions in mutants of the green alga Chlamydomonas reinhardtii will be discussed.

  18. Biomolecular electrostatics and solvation: a computational perspective

    PubMed Central

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

    2012-01-01

    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 towards 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 nonpolar behavior) in order to provide a background to understand the different types of solvation models. PMID:23217364

  19. IR and py/GC/MS examination of amber relics excavated from 6th century royal tomb in Korean Peninsula

    NASA Astrophysics Data System (ADS)

    Park, Jongseo; Yun, Eunyoung; Kang, Hyungtae; Ahn, Jooyoung; Kim, Gyuho

    2016-08-01

    Relics of amber were excavated from King Muryeong's tomb constructed in the 6th century on the Korean peninsula. To estimate the provenance, FTIR (Fourier transform infrared spectroscopy) and py/GC/MS (pyrolysis/gas chromatography/mass spectrometry) analysis were utilized. The reference Baltic amber sample was also analyzed with the same method for comparison. The relics were confirmed to be amber from the FTIR analysis where an absorption band near 1150 cm- 1, characteristic one in Baltic amber, was also observed. In py/GC/MS analysis, pyrolyzed products like butanedioic acid and dehydroabietic acid, known constituents of amber, were observed. In addition, D-fenchyl alcohol, camphor, borneol and butanedioic acid, typical constituents of Baltic amber, were observed in some samples. From this, it appears that some of relics were made from Baltic amber and that Baltic amber was transported to the Korean peninsula in the time of tomb construction.

  20. IR and py/GC/MS examination of amber relics excavated from 6th century royal tomb in Korean Peninsula.

    PubMed

    Park, Jongseo; Yun, Eunyoung; Kang, Hyungtae; Ahn, Jooyoung; Kim, Gyuho

    2016-08-01

    Relics of amber were excavated from King Muryeong's tomb constructed in the 6th century on the Korean peninsula. To estimate the provenance, FTIR (Fourier transform infrared spectroscopy) and py/GC/MS (pyrolysis/gas chromatography/mass spectrometry) analysis were utilized. The reference Baltic amber sample was also analyzed with the same method for comparison. The relics were confirmed to be amber from the FTIR analysis where an absorption band near 1150cm(-1), characteristic one in Baltic amber, was also observed. In py/GC/MS analysis, pyrolyzed products like butanedioic acid and dehydroabietic acid, known constituents of amber, were observed. In addition, d-fenchyl alcohol, camphor, borneol and butanedioic acid, typical constituents of Baltic amber, were observed in some samples. From this, it appears that some of relics were made from Baltic amber and that Baltic amber was transported to the Korean peninsula in the time of tomb construction. PMID:27116473

  1. Biomolecular decision-making process for self assembly.

    SciTech Connect

    Osbourn, Gordon Cecil

    2005-01-01

    The brain is often identified with decision-making processes in the biological world. In fact, single cells, single macromolecules (proteins) and populations of molecules also make simple decisions. These decision processes are essential to survival and to the biological self-assembly and self-repair processes that we seek to emulate. How do these tiny systems make effective decisions? How do they make decisions in concert with a cooperative network of other molecules or cells? How can we emulate the decision-making behaviors of small-scale biological systems to program and self-assemble microsystems? This LDRD supported research to answer these questions. Our work included modeling and simulation of protein populations to help us understand, mimic, and categorize molecular decision-making mechanisms that nonequilibrium systems can exhibit. This work is an early step towards mimicking such nanoscale and microscale biomolecular decision-making processes in inorganic systems.

  2. An ant-associated mesostigmatid mite in Baltic amber

    PubMed Central

    Dunlop, Jason A.; Kontschán, Jenő; Walter, David E.; Perrichot, Vincent

    2014-01-01

    Fossil mesostigmatid mites (Acari: Parasitiformes: Mesostigmata) are extremely rare, and specimens from only nine families, including four named species, have been described so far. A new record of Myrmozercon sp. described here from Eocene (ca 44–49 Myr) Baltic amber represents the first—and so far only—fossil example of the derived, extant family Laelapidae. Significantly, modern species of this genus are habitually myrmecophilous and the fossil mite described here is preserved attached to the head of the dolichoderine ant Ctenobethylus goepperti (Mayr, 1868). It thus offers the oldest unequivocal evidence for an ecological association between mesostigmatid mites and social insects in the order Hymenoptera. PMID:25209198

  3. A gilled mushroom, Gerontomyces lepidotus gen. et sp. nov. (Basidiomycota: Agaricales), in Baltic amber.

    PubMed

    Poinar, George

    2016-09-01

    A densely scaled small mushroom in Baltic amber is described as Gerontomyces lepidotus gen. et sp. nov. and is characterized by a convex pileus 1.0 mm in diameter, distant to subdistant lamellae with smooth margins and a centrally inserted cylindrical, solid stipe. Its taxonomic placement is uncertain. This is the first mushroom described from Baltic amber. PMID:27567715

  4. A remarkable fossil leptosaldine bug from Mid-Cretaceous Burmese amber (Hemiptera: Heteroptera: Leptopodomorpha: Leptopodidae).

    PubMed

    Popov, Yuri A; Heiss, Ernst

    2016-01-01

    A new genus and species of leptosaldine bugs, Leptosaldinea cobbeni gen. et sp. nov. (Hemiptera: Heteroptera: Leptopodidae) is described and illustrated from Burmese Middle Cretaceous (Albian-Cenomanian) amber found in Kachin State, northern Myanmar. This is the third record of a leptosaldine bug from Burmese amber. A brief analysis of the characters and systematic relationships of Leptosaldinae is provided. PMID:27470718

  5. Forcefield_PTM: Ab Initio Charge and AMBER Forcefield Parameters for Frequently Occurring Post-Translational Modifications

    PubMed Central

    Khoury, George A.; Thompson, Jeff P.; Smadbeck, James; Kieslich, Chris A.; Floudas, Christodoulos A.

    2014-01-01

    In this work, we introduce Forcefield_PTM, a set of AMBER forcefield parameters consistent with ff03 for 32 common post-translational modifications. Partial charges were calculated through ab initio calculations and a two-stage RESP-fitting procedure in an ether-like implicit solvent environment. The charges were found to be generally consistent with others previously reported for phosphorylated amino acids, and trimethyllysine, using different parameterization methods. Pairs of modified and their corresponding unmodified structures were curated from the PDB for both single and multiple modifications. Background structural similarity was assessed in the context of secondary and tertiary structures from the global dataset. Next, the charges derived for Forcefield_PTM were tested on a macroscopic scale using unrestrained all-atom Langevin molecular dynamics simulations in AMBER for 34 (17 pairs of modified/unmodified) systems in implicit solvent. Assessment was performed in the context of secondary structure preservation, stability in energies, and correlations between the modified and unmodified structure trajectories on the aggregate. As an illustration of their utility, the parameters were used to compare the structural stability of the phosphorylated and dephosphorylated forms of OdhI. Microscopic comparisons between quantum and AMBER single point energies along key χ torsions on several PTMs were performed and corrections to improve their agreement in terms of mean squared errors and squared correlation coefficients were parameterized. This forcefield for post-translational modifications in condensed-phase simulations can be applied to a number of biologically relevant and timely applications including protein structure prediction, protein and peptide design, docking, and to study the effect of PTMs on folding and dynamics. We make the derived parameters and an associated interactive webtool capable of performing post-translational modifications on proteins

  6. Forcefield_PTM: Ab Initio Charge and AMBER Forcefield Parameters for Frequently Occurring Post-Translational Modifications.

    PubMed

    Khoury, George A; Thompson, Jeff P; Smadbeck, James; Kieslich, Chris A; Floudas, Christodoulos A

    2013-12-10

    In this work, we introduce Forcefield_PTM, a set of AMBER forcefield parameters consistent with ff03 for 32 common post-translational modifications. Partial charges were calculated through ab initio calculations and a two-stage RESP-fitting procedure in an ether-like implicit solvent environment. The charges were found to be generally consistent with others previously reported for phosphorylated amino acids, and trimethyllysine, using different parameterization methods. Pairs of modified and their corresponding unmodified structures were curated from the PDB for both single and multiple modifications. Background structural similarity was assessed in the context of secondary and tertiary structures from the global dataset. Next, the charges derived for Forcefield_PTM were tested on a macroscopic scale using unrestrained all-atom Langevin molecular dynamics simulations in AMBER for 34 (17 pairs of modified/unmodified) systems in implicit solvent. Assessment was performed in the context of secondary structure preservation, stability in energies, and correlations between the modified and unmodified structure trajectories on the aggregate. As an illustration of their utility, the parameters were used to compare the structural stability of the phosphorylated and dephosphorylated forms of OdhI. Microscopic comparisons between quantum and AMBER single point energies along key χ torsions on several PTMs were performed and corrections to improve their agreement in terms of mean squared errors and squared correlation coefficients were parameterized. This forcefield for post-translational modifications in condensed-phase simulations can be applied to a number of biologically relevant and timely applications including protein structure prediction, protein and peptide design, docking, and to study the effect of PTMs on folding and dynamics. We make the derived parameters and an associated interactive webtool capable of performing post-translational modifications on proteins

  7. Brachyceran Diptera (Insecta) in Cretaceous ambers, Part IV, Significant New Orthorrhaphous Taxa

    PubMed Central

    Grimaldi, David A.; Arillo, Antonio; Cumming, Jeffrey M.; Hauser, Martin

    2011-01-01

    Abstract Thirteen species of basal Brachycera (11 described as new) are reported, belonging to nine families and three infraorders. They are preserved in amber from the Early Cretaceous (Neocomian) of Lebanon, Albian of northern Spain, upper Albian to lower Cenomanian of northern Myanmar, and Late Cretaceous of New Jersey USA (Turonian) and Alberta, Canada (Campanian). Taxa are as follows, with significance as noted: In Stratiomyomorpha: Stratiomyidae (Cretaceogaster pygmaeus Teskey [2 new specimens in Canadian amber], Lysistrata emerita Grimaldi & Arillo, gen. et sp. n. [stem-group species of the family in Spanish amber]), and Xylomyidae (Cretoxyla azari Grimaldi & Cumming, gen. et sp. n. [in Lebanese amber], and an undescribed species from Spain). In Tabanomorpha: Tabanidae (Cratotabanus newjerseyensis Grimaldi, sp. n., in New Jersey amber). In Muscomorpha: Acroceridae (Schlingeromyia minuta Grimaldi & Hauser, gen. et sp. n. and Burmacyrtus rusmithi Grimaldi & Hauser gen. et sp. n., in Burmese amber, the only definitive species of the family from the Cretaceous); Mythicomyiidae (Microburmyia analvena Grimaldi & Cumming gen. et sp. n. and Microburmyia veanalvena Grimaldi & Cumming, sp. n., stem-group species of the family, both in Burmese amber); Apsilocephalidae or near (therevoid family-group) (Kumaromyia burmitica Grimaldi & Hauser, gen. et sp. n. [in Burmese amber]); Apystomyiidae (Hilarimorphites burmanica Grimaldi & Cumming, sp. n. [in Burmese amber], whose closest relatives are from the Late Jurassic of Kazachstan, the Late Cretaceous of New Jersey, and Recent of California). Lastly, two species belonging to families incertae sedis, both in Burmese amber: Tethepomyiidae (Tethepomyia zigrasi Grimaldi & Arillo sp. n., the aculeate oviscapt of which indicates this family was probably parasitoidal and related to Eremochaetidae); and unplaced to family is Myanmyia asteiformia Grimaldi, gen. et sp. n., a minute fly with highly reduced venation. These new taxa

  8. New and revised maimetshid wasps from Cretaceous ambers (Hymenoptera, Maimetshidae)

    PubMed Central

    Perrichot, Vincent; Ortega-Blanco, Jaime; McKellar, Ryan C.; Delclòs, Xavier; Azar, Dany; Nel, André; Tafforeau, Paul; Engel, Michael S.

    2011-01-01

    Abstract New material of the wasp family Maimetshidae (Apocrita) is presented from four Cretaceous amber deposits – the Neocomian of Lebanon, the Early Albian of Spain, the latest Albian/earliest Cenomanian of France, and the Campanian of Canada. The new record from Canadian Cretaceous amber extends the temporal and paleogeographical range of the family. New material from France is assignable to Guyotemaimetsha enigmatica Perrichot et al. including the first females for the species, while a series of males and females from Spain are described and figured as Iberomaimetsha Ortega-Blanco, Perrichot & Engel, gen. n., with the two new species Iberomaimetsha rasnitsyni Ortega-Blanco, Perrichot & Engel, sp. n. and Iberomaimetsha nihtmara Ortega-Blanco, Delclòs & Engel, sp. n.; a single female from Lebanon is described and figured as Ahiromaimetsha najlae Perrichot, Azar, Nel & Engel, gen. et sp. n., and a single male from Canada is described and figured as Ahstemiam cellula McKellar & Engel, gen. et sp. n. The taxa are compared with other maimetshids, a key to genera and species is given, and brief comments made on the family. PMID:22259291

  9. Historical survey of the internal use of unprocessed amber.

    PubMed

    Duffin, Christofer J

    2015-01-01

    The organic mineraloid gemstone, amber, a fossilized resin collected from Eocene deposits laid down around 44 million years old on the Baltic coast, has been an important geopharmaceutical in the western materia medica since classical times. Once rendered into powdered form, it could be delivered into the body using a wide range of vehicles including lozenges, pills, tablets, troches, electuaries, solutions and lohochs (lick-pots), and with toast and poached eggs. Acting either alone or in combination with a wide range of botanical, zoological and other geological ingredients, it was employed in the treatment of a huge range of diseases. Most prominent among these were various vascular disorders (e.g. haemoptysis, haemorrhage, excessive menstrual bleeding), problems with the urogenital system (e.g. tendency towards miscarriage, impotence, venereal diseases, strangury, dysuria and bladder stones) and alimentary conditions, particularly dysentery. A variety of infectious diseases, including plague, gonorrhoea, measles and fevers could be targeted with amber-containing preparations, as could epilepsy, melancholy and the ravages of old age. Rather more unusual applications included its use in the treatment of impotence, halitosis, drunkenness and a weak back. PMID:26203539

  10. Nanoarchitectonics of biomolecular assemblies for functional applications

    NASA Astrophysics Data System (ADS)

    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.

  11. Analyzing biomolecular interactions by variable angle ellipsometry

    NASA Astrophysics Data System (ADS)

    Wu, Jiun-Yan; Lee, Chih-Kung; Lee, J. H.; Shiue, Shuen-Chen; Lee, Shu-Sheng; Lin, Shiming

    2001-10-01

    In this paper, an innovative ellipsometer is developed and applied to metrology of the biomolecular interaction on a protein biochip. Both the theory, optical and opto-mechanical configurations of this newly developed ellipsometer and methodologies adopted in system design to improve the system performance are presented. It will be shown that by measuring the ellipsometric parameters, the corresponding concentration variation in biochemical reaction can be calculated according to stoichiometry analysis. By applying the variable angle ellipsometry to analysis of a multi-layered sample, the thickness and concentration are resolved. It is believed that the newly developed ellipsometer biosensor is able to undertake an accurate measurement on biomedical interaction.

  12. Thermodynamic Uncertainty Relation for Biomolecular Processes

    NASA Astrophysics Data System (ADS)

    Barato, Andre C.; Seifert, Udo

    2015-04-01

    Biomolecular systems like molecular motors or pumps, transcription and translation machinery, and other enzymatic reactions, can be described as Markov processes on a suitable network. We show quite generally that, in a steady state, the dispersion of observables, like the number of consumed or produced molecules or the number of steps of a motor, is constrained by the thermodynamic cost of generating it. An uncertainty ɛ requires at least a cost of 2 kBT /ɛ2 independent of the time required to generate the output.

  13. Photochemical concepts on the origin of biomolecular asymmetry.

    PubMed

    Meierhenrich, Uwe J; Thiemann, Wolfram H P

    2004-02-01

    Biopolymers like DNA and proteins are strongly selective towards the chirality of their monomer units. The use of homochiral monomers is regarded as essential for the construction and function of biopolymers; the emergence of the molecular asymmetry is therefore considered as a fundamental step in Chemical Evolution. This work focuses on physicochemical mechanisms for the origin of biomolecular asymmetry. Very recently two groups, one from Allamandola at NASA Ames and the other from our Inter-European team, demonstrated simultaneously the spontaneous photoformation of a variety of chiral amino acid structures under simulated interstellar conditions. Since both groups used unpolarized light for the photoreaction the obtained amino acids turned out racemic as expected. The obtained experimental data support the assumption that tiny ice grains can furthermore play host to important asymmetric reactions when irradiated by interstellar circularly polarized ultraviolet light. It is possible that such ice grains could have become incorporated into the early cloud that formed our Solar System and ended up on Earth, assisting life to start. Several lines of evidence suggest that some of the building blocks of life were delivered to the primitive Earth via (micro-) meteoroids and/or comets. These results suggest that asymmetric interstellar photochemistry may have played a significant part in supplying Earth with some of the enantioenriched organic materials needed to trigger life. The search for the origin of biomolecular homochirality leads to a strong interest in the fields of asymmetric photochemistry with special emphasis on absolute asymmetric synthesis. We outline here the theoretical background on asymmetric interstellar ice photochemistry, summarize recent concepts and advances in the field, and discuss briefly its implications. The obtained data are crucial for the design of the enantioselective COSAC GC-MS experiment onboard the ROSETTA spacecraft to a comet to be

  14. At least 10% shorter C–H bonds in cryogenic protein crystal structures than in current AMBER forcefields

    SciTech Connect

    Pang, Yuan-Ping

    2015-03-06

    High resolution protein crystal structures resolved with X-ray diffraction data at cryogenic temperature are commonly used as experimental data to refine forcefields and evaluate protein folding simulations. However, it has been unclear hitherto whether the C–H bond lengths in cryogenic protein structures are significantly different from those defined in forcefields to affect protein folding simulations. This article reports the finding that the C–H bonds in high resolution cryogenic protein structures are 10–14% shorter than those defined in current AMBER forcefields, according to 3709 C–H bonds in the cryogenic protein structures with resolutions of 0.62–0.79 Å. Also, 20 all-atom, isothermal–isobaric, 0.5-μs molecular dynamics simulations showed that chignolin folded from a fully-extended backbone formation to the native β-hairpin conformation in the simulations using AMBER forcefield FF12SB at 300 K with an aggregated native state population including standard error of 10 ± 4%. However, the aggregated native state population with standard error reduced to 3 ± 2% in the same simulations except that C–H bonds were shortened by 10–14%. Furthermore, the aggregated native state populations with standard errors increased to 35 ± 3% and 26 ± 3% when using FF12MC, which is based on AMBER forcefield FF99, with and without the shortened C–H bonds, respectively. These results show that the 10–14% bond length differences can significantly affect protein folding simulations and suggest that re-parameterization of C–H bonds according to the cryogenic structures could improve the ability of a forcefield to fold proteins in molecular dynamics simulations. - Highlights: • Cryogenic crystal structures are commonly used in computational studies of proteins. • C–H bonds in the cryogenic structures are shorter than those defined in forcefields. • A survey of 3709 C–H bonds shows that the cryogenic bonds are 10–14% shorter. • The

  15. Empirical Corrections to the Amber RNA Force Field with Target Metadynamics.

    PubMed

    Gil-Ley, Alejandro; Bottaro, Sandro; Bussi, Giovanni

    2016-06-14

    The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the α and ζ backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement. PMID:27153317

  16. Empirical Corrections to the Amber RNA Force Field with Target Metadynamics

    PubMed Central

    2016-01-01

    The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the α and ζ backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement. PMID:27153317

  17. Smartphones for cell and biomolecular detection.

    PubMed

    Liu, Xiyuan; Lin, Tung-Yi; Lillehoj, Peter B

    2014-11-01

    Recent advances in biomedical science and technology have played a significant role in the development of new sensors and assays for cell and biomolecular detection. Generally, these efforts are aimed at reducing the complexity and costs associated with diagnostic testing so that it can be performed outside of a laboratory or hospital setting, requiring minimal equipment and user involvement. In particular, point-of-care (POC) testing offers immense potential for many important applications including medical diagnosis, environmental monitoring, food safety, and biosecurity. When coupled with smartphones, POC systems can offer portability, ease of use and enhanced functionality while maintaining performance. This review article focuses on recent advancements and developments in smartphone-based POC systems within the last 6 years with an emphasis on cell and biomolecular detection. These devices typically comprise multiple components, such as detectors, sample processors, disposable chips, batteries, and software, which are integrated with a commercial smartphone. One of the most important aspects of developing these systems is the integration of these components onto a compact and lightweight platform that requires minimal power. Researchers have demonstrated several promising approaches employing various detection schemes and device configurations, and it is expected that further developments in biosensors, battery technology and miniaturized electronics will enable smartphone-based POC technologies to become more mainstream tools in the scientific and biomedical communities. PMID:24916841

  18. Coassembly of aromatic dipeptides into biomolecular necklaces.

    PubMed

    Yuran, Sivan; Razvag, Yair; Reches, Meital

    2012-11-27

    This paper describes the formation of complex peptide-based structures by the coassembly of two simple peptides, the diphenylalanine peptide and its tert-butyl dicarbonate (Boc) protected analogue. Each of these peptides can self-assemble into a distinct architecture: the diphenylalanine peptide into tubular structures and its analogue into spheres. Integrated together, these peptides coassemble into a construction of beaded strings, where spherical assemblies are connected by elongated elements. Electron and scanning force microscopy demonstrated the morphology of these structures, which we termed "biomolecular necklaces". Additional experiments indicated the reversibility of the coassembly process and the stability of the structures. Furthermore, we suggest a possible mechanism of formation for the biomolecular necklaces. Our suggestion is based on the necklace model for polyelectrolyte chains, which proposes that a necklace structure appears as a result of counterion condensation on the backbone of a polyelectrolyte. Overall, the approach of coassembly, demonstrated using aromatic peptides, can be adapted to any peptides and may lead to the development and discovery of new self-assembled architectures formed by peptides and other biomolecules. PMID:23061818

  19. Molecular dynamics simulations of a new branched antimicrobial peptide: A comparison of force fields

    NASA Astrophysics Data System (ADS)

    Li, Jianguo; Lakshminarayanan, Rajamani; Bai, Yang; Liu, Shouping; Zhou, Lei; Pervushin, Konstantin; Verma, Chandra; Beuerman, Roger W.

    2012-12-01

    Branched antimicrobial peptides are promising as a new class of antibiotics displaying high activity and low toxicity and appear to work through a unique mechanism of action. We explore the structural dynamics of a covalently branched 18 amino acid peptide (referred to as B2088) in aqueous and membrane mimicking environments through molecular dynamics (MD) simulations. Towards this, we carry out conventional MD simulations and supplement these with replica exchange simulations. The simulations are carried out using four different force fields that are commonly employed for simulating biomolecular systems. These force fields are GROMOS53a6, CHARMM27 with cMAP, CHARMM27 without cMAP and AMBER99sb. The force fields are benchmarked against experimental data available from circular dichroism and nuclear magnetic resonance spectroscopies, and show that CHARMM27 without cMAP correction is the most successful in reproducing the structural dynamics of B2088 both in water and in the presence of micelles. Although the four force fields predict different structures of B2088, they all show that B2088 stabilizes against the head group of the lipid through hydrogen bonding of its Lys and Arg side chains. This leads us to hypothesize that B2088 is unlikely to penetrate into the hydrophobic region of the membrane owing to the high free energy costs of transfer from water, and possibly acts by carpeting and thus disrupting the membrane.

  20. Optimization of an AMBER Force Field for the Artificial Nucleic Acid, LNA, and Benchmarking with NMR of L(CAAU)

    PubMed Central

    2013-01-01

    Locked Nucleic Acids (LNAs) are RNA analogues with an O2′-C4′ methylene bridge which locks the sugar into a C3′-endo conformation. This enhances hybridization to DNA and RNA, making LNAs useful in microarrays and potential therapeutics. Here, the LNA, L(CAAU), provides a simplified benchmark for testing the ability of molecular dynamics (MD) to approximate nucleic acid properties. LNA χ torsions and partial charges were parametrized to create AMBER parm99_LNA. The revisions were tested by comparing MD predictions with AMBER parm99 and parm99_LNA against a 200 ms NOESY NMR spectrum of L(CAAU). NMR indicates an A-Form equilibrium ensemble. In 3000 ns simulations starting with an A-form structure, parm99_LNA and parm99 provide 66% and 35% agreement, respectively, with NMR NOE volumes and 3J-couplings. In simulations of L(CAAU) starting with all χ torsions in a syn conformation, only parm99_LNA is able to repair the structure. This implies methods for parametrizing force fields for nucleic acid mimics can reasonably approximate key interactions and that parm99_LNA will improve reliability of MD studies for systems with LNA. A method for approximating χ population distribution on the basis of base to sugar NOEs is also introduced. PMID:24377321

  1. The aquatic and semiaquatic biota in Miocene amber from the Campo LA Granja mine (Chiapas, Mexico): Paleoenvironmental implications

    NASA Astrophysics Data System (ADS)

    Serrano-Sánchez, María de Lourdes; Hegna, Thomas A.; Schaaf, Peter; Pérez, Liseth; Centeno-García, Elena; Vega, Francisco J.

    2015-10-01

    Amber from the Campo La Granja mine in Chiapas, Mexico, is distinct from other sources of amber in Chiapas. Campo La Granja amber has distinct layers created by successive flows of resin with thin layers of sand on most surfaces. Aquatic and semi-aquatic arthropods are commonly found. Together these pieces of evidence suggest an estuarine environment similar to modern mangrove communities. The aquatic crustaceans are the most intriguing aspect of the biota. A large number of ostracods have been found in the amber-many with their carapaces open, suggesting that they were alive and submerged in water at the time of entombment. The only known examples of brachyuran crabs preserved in amber are found in the Campo La Granja amber. Amphipods, copepods, isopods, and tanaids are also members of the crustacean fauna preserved in amber.

  2. Entrapment Bias of Arthropods in Miocene Amber Revealed by Trapping Experiments in a Tropical Forest in Chiapas, Mexico

    PubMed Central

    Solórzano Kraemer, Mónica M.; Kraemer, Atahualpa S.; Stebner, Frauke; Bickel, Daniel J.; Rust, Jes

    2015-01-01

    All entomological traps have a capturing bias, and amber, viewed as a trap, is no exception. Thus the fauna trapped in amber does not represent the total existing fauna of the former amber forest, rather the fauna living in and around the resin producing tree. In this paper we compare arthropods from a forest very similar to the reconstruction of the Miocene Mexican amber forest, and determine the bias of different trapping methods, including amber. We also show, using cluster analyses, measurements of the trapped arthropods, and guild distribution, that the amber trap is a complex entomological trap not comparable with a single artificial trap. At the order level, the most similar trap to amber is the sticky trap. However, in the case of Diptera, at the family level, the Malaise trap is also very similar to amber. Amber captured a higher diversity of arthropods than each of the artificial traps, based on our study of Mexican amber from the Middle Miocene, a time of climate optimum, where temperature and humidity were probably higher than in modern Central America. We conclude that the size bias is qualitatively independent of the kind of trap for non–extreme values. We suggest that frequent specimens in amber were not necessarily the most frequent arthropods in the former amber forest. Selected taxa with higher numbers of specimens appear in amber because of their ecology and behavior, usually closely related with a tree–inhabiting life. Finally, changes of diversity from the Middle Miocene to Recent time in Central and South America can be analyzed by comparing the rich amber faunas from Mexico and the Dominican Republic with the fauna trapped using sticky and Malaise traps in Central America. PMID:25785584

  3. Design of environment-responsive biomolecular systems

    NASA Astrophysics Data System (ADS)

    Aizawa, Masuo; Niimi, T.; Haruyama, T.; Kobatake, E.

    1996-02-01

    Two different types of biomolecular network systems have been designed to respond to the environmental conditions. One is the calmodulin and enzyme (phosphodiesterase, PDE) that activates phosphodiesterase through the conformational change in responding calcium ion. Calmodulin was genetically engineered to be fused with glutathione-S-transferase (GST). Calmodulin/GST fused protein was self-assembled on the gold surface through glutathione. The calmodulin/GST protein layer exhibited an ability to modulate the PDE activity in a solution phase depending on the calcium ion concentration. The other is the engineered gene structure that produces firefly luciferase in responding environmental pollutants. A TOL plasmid, encoding a binding protein xyl R for xyline and a marker enzyme firefly luciferase, has been implemented in a bacterial cell. The whole cell responded to environmentally hazardous substances such as xylene in emitting light.

  4. Biomolecular Imaging with Coherent Nonlinear Vibrational Microscopy

    PubMed Central

    Chung, Chao-Yu; Boik, John; Potma, Eric O.

    2014-01-01

    Optical imaging with spectroscopic vibrational contrast is a label-free solution for visualizing, identifying, and quantifying a wide range of biomolecular compounds in biological materials. Both linear and nonlinear vibrational microscopy techniques derive their imaging contrast from infrared active or Raman allowed molecular transitions, which provide a rich palette for interrogating chemical and structural details of the sample. Yet nonlinear optical methods, which include both second-order sum-frequency generation (SFG) and third-order coherent Raman scattering (CRS) techniques, offer several improved imaging capabilities over their linear precursors. Nonlinear vibrational microscopy features unprecedented vibrational imaging speeds, provides strategies for higher spatial resolution, and gives access to additional molecular parameters. These advances have turned vibrational microscopy into a premier tool for chemically dissecting live cells and tissues. This review discusses the molecular contrast of SFG and CRS microscopy and highlights several of the advanced imaging capabilities that have impacted biological and biomedical research. PMID:23245525

  5. Biomolecular Structure Determination with Divide and Concur

    NASA Astrophysics Data System (ADS)

    Kallus, Yoav; Elser, Veit

    2009-03-01

    Divide and concur (D-C) is a general computational approach, designed for the solution of highly frustrated problems. Recently applied to the problems of disk packing, the kissing number problem, and 3-SAT, it was competitive or outperformed special-purpose methods.ootnotetextS. Gravel and V. Elser, Phys. Rev. E 78, 036706 (2008) We present a method for applying the D-C framework to the problem of biomolecular structure determination. From a list of geometric constraints on groups of atoms in the molecule, we construct a deterministic iterative map that efficiently searches for structures simultaneously satisfying all constraints. As our method eschews an energy function and its minimization to focus on geometric constraints, it can very naturally integrate with the geometric constraints due to chemistry and physics, experimental constraints due to NMR data or many other experimental or biological hints. We present some results of our method.

  6. Micro- and nanodevices integrated with biomolecular probes.

    PubMed

    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. PMID:26363089

  7. Micro- and nanodevices integrated with biomolecular probes

    PubMed Central

    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

  8. Semisynthetic and Biomolecular Hydrogen Evolution Catalysts.

    PubMed

    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. PMID:26671416

  9. Band structure and optical properties of amber studied by first principles

    NASA Astrophysics Data System (ADS)

    Rao, Zhi-Fan; Zhou, Rong-Feng

    2013-03-01

    The band structure and density of states of amber is studied by the first principles calculation based on density of functional theory. The complex structure of amber has 214 atoms and the band gap is 5.0 eV. The covalent bond is combined C/O atoms with H atoms. The O 2p orbital is the biggest effect near the Fermi level. The optical properties' results show that the reflectivity is low, and the refractive index is 1.65 in visible light range. The highest absorption coefficient peak is at 172 nm and another higher peak is at 136 nm. These convince that the amber would have a pretty sheen and that amber is a good and suitable crystal for jewelry and ornaments.

  10. Natural amber, copal resin and colophony investigated by UV-VIS, infrared and Raman spectrum

    NASA Astrophysics Data System (ADS)

    Rao, ZhiFan; Dong, Kun; Yang, XiaoYun; Lin, JinChang; Cui, XiaoYing; Zhou, RongFeng; Deng, Qing

    2013-08-01

    Natural amber, copal resin and colophony are have investigated by UV-VIS, infrared and Raman spectrum. In order to distinguish the natural amber, copal resin and colophony, we have successfully used the nondestructive examination (NDE) technology. The results show that UV-VIS could not distinguish these compositions. The infrared spectra can distinguish them, but the technology may destroy the specimen. The Raman spectra show three characteristic peaks of vibration near position 932 cm-1 and position 1179 cm-1 of copal resin, which confirm the existence of terpenes compounds in it. In the Raman spectra of colophony, the vibration characteristic peak at position 1589 cm-1, caused by the conjugate double bond of internal unsaturated resin acid, is the basis of the characteristic difference between colophony and natural amber. The advantages of the distinguished technology by Raman spectroscopy are convenient and nondestructive examination for natural amber, copal resin and colophony.

  11. The general AMBER force field (GAFF) can accurately predict thermodynamic and transport properties of many ionic liquids.

    PubMed

    Sprenger, K G; Jaeger, Vance W; Pfaendtner, Jim

    2015-05-01

    We have applied molecular dynamics to calculate thermodynamic and transport properties of a set of 19 room-temperature ionic liquids. Since accurately simulating the thermophysical properties of solvents strongly depends upon the force field of choice, we tested the accuracy of the general AMBER force field, without refinement, for the case of ionic liquids. Electrostatic point charges were developed using ab initio calculations and a charge scaling factor of 0.8 to more accurately predict dynamic properties. The density, heat capacity, molar enthalpy of vaporization, self-diffusivity, and shear viscosity of the ionic liquids were computed and compared to experimentally available data, and good agreement across a wide range of cation and anion types was observed. Results show that, for a wide range of ionic liquids, the general AMBER force field, with no tuning of parameters, can reproduce a variety of thermodynamic and transport properties with similar accuracy to that of other published, often IL-specific, force fields. PMID:25853313

  12. The Range of Bioinclusions and Pseudoinclusions Preserved in a New Turonian (~90 Ma) Amber Occurrence from Southern Australia

    PubMed Central

    Quinney, Annie; Mays, Chris; Stilwell, Jeffrey D.; Zelenitsky, Darla K.; Therrien, François

    2015-01-01

    A new Turonian amber occurrence, representing the oldest in situ amber locality in Australia and the southern-most locality in Gondwana, has recently been discovered in the Otway Basin of Victoria. The amber was collected from petroleum cores and many pieces contain a range of inclusions that can provide information on the depositional history of the resin. To date, one species of fern spore (Cyathidites minor) and one species of lycophyte spore (Kraeuselisporites sp?) have been conclusively identified in the amber, along with filamentous microorganisms and degraded plant matter. Several samples are also rife with pseudoinclusions as reported recently in other ambers. The abundance of preserved particulate debris and wind dispersed spores suggest that the Otway amber formed subaerially. Furthermore, based on the range of bioinclusions and forms of pseudoinclusions preserved within a single piece of amber, the locus of hardening for individual samples is variably interpreted as occurring in the tree tops, on the tree trunk or on the ground surface. Notably, specific inclusion assemblages are associated with certain colours of amber. By extension, and in accordance with recent studies, amber colour may be indicative of depositional environment. Variation in the environment of solidification may, therefore, be sufficient to account for the broad range of morphological characteristics preserved in a single amber deposit. PMID:25970501

  13. The range of bioinclusions and pseudoinclusions preserved in a new Turonian (~90 ma) amber occurrence from Southern Australia.

    PubMed

    Quinney, Annie; Mays, Chris; Stilwell, Jeffrey D; Zelenitsky, Darla K; Therrien, François

    2015-01-01

    A new Turonian amber occurrence, representing the oldest in situ amber locality in Australia and the southern-most locality in Gondwana, has recently been discovered in the Otway Basin of Victoria. The amber was collected from petroleum cores and many pieces contain a range of inclusions that can provide information on the depositional history of the resin. To date, one species of fern spore (Cyathidites minor) and one species of lycophyte spore (Kraeuselisporites sp?) have been conclusively identified in the amber, along with filamentous microorganisms and degraded plant matter. Several samples are also rife with pseudoinclusions as reported recently in other ambers. The abundance of preserved particulate debris and wind dispersed spores suggest that the Otway amber formed subaerially. Furthermore, based on the range of bioinclusions and forms of pseudoinclusions preserved within a single piece of amber, the locus of hardening for individual samples is variably interpreted as occurring in the tree tops, on the tree trunk or on the ground surface. Notably, specific inclusion assemblages are associated with certain colours of amber. By extension, and in accordance with recent studies, amber colour may be indicative of depositional environment. Variation in the environment of solidification may, therefore, be sufficient to account for the broad range of morphological characteristics preserved in a single amber deposit. PMID:25970501

  14. GLYCAM06: a generalizable biomolecular force field. Carbohydrates.

    PubMed

    Kirschner, Karl N; Yongye, Austin B; Tschampel, Sarah M; González-Outeiriño, Jorge; Daniels, Charlisa R; Foley, B Lachele; Woods, Robert J

    2008-03-01

    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 alpha- and beta-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

  15. GLYCAM06: A Generalizable Biomolecular Force Field. Carbohydrates

    PubMed Central

    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

  16. Examination of the quality of various force fields and solvation models for the equilibrium simulations of GA88 and GB88.

    PubMed

    Zeng, Juan; Li, Yongxiu; Zhang, John Z H; Mei, Ye

    2016-08-01

    Elucidating the relationship between sequence and conformation is essential for the understanding of functions of proteins. While sharing 88 % sequence identity and differing by only seven residues, GA88 and GB88 have completely different structures and serve as ideal systems for investigating the relationship between sequence and function. Benefiting from the continuous advancement of the computational ability of modern computers, molecular dynamics (MD) simulation is now playing an increasingly important role in the study of proteins. However, the reliability of MD simulations is limited by the accuracy of the force fields and solvent model approximations. In this work, several AMBER force fields (AMBER03, AMBER99SB, AMBER12SB, AMBER14SB, AMBER96) and solvent models (TIP3P, IGB5, IGB7, IGB8) have been employed in the simulations of GA88 and GB88. The statistical results from 19 simulations show that GA88 and GB88 both adopt more compact structures than the native structures. GB88 is more stable than GA88 regardless of the force fields and solvent models utilized. Most of the simulations overestimated the salt bridge interaction. The combination of AMBER14SB force field and IGB8 solvent model shows the best overall performance in the simulations of both GA88 and GB88. AMBER03 and AMBER12SB also yield reasonable results but only in the TIP3P explicit solvent model. PMID:27392746

  17. New Fossil Scorpion from the Chiapas Amber Lagerstätte

    PubMed Central

    Riquelme, Francisco; Villegas-Guzmán, Gabriel; González-Santillán, Edmundo; Córdova-Tabares, Víctor; Francke, Oscar F.; Piedra-Jiménez, Dulce; Estrada-Ruiz, Emilio; Luna-Castro, Bibiano

    2015-01-01

    A new species of scorpion is described based on a rare entire adult male preserved in a cloudy amber from Miocene rocks in the Chiapas Highlands, south of Mexico. The amber-bearing beds in Chiapas constitute a Conservation Lagerstätte with outstanding organic preservation inside plant resin. The new species is diagnosed as having putative characters that largely correspond with the genus Tityus Koch, 1836 (Scorpiones, Buthidae). Accordingly, it is now referred to as Tityus apozonalli sp. nov. Its previously unclear phylogenetic relationship among fossil taxa of the family Buthidae from both Dominican and Mexican amber is also examined herein. Preliminarily results indicate a basal condition of T. apozonalli regarding to Tityus geratus Santiago-Blay and Poinar, 1988, Tityus (Brazilotityus) hartkorni Lourenço, 2009, and Tityus azari Lourenço, 2013 from Dominican amber, as was Tityus (Brazilotityus) knodeli Lourenço, 2014 from Mexican amber. Its close relationships with extant Neotropic Tityus-like subclades such as ‘Tityus clathratus’ and the subgenus Tityus (Archaeotityus) are also discussed. This new taxon adds to the knowledge of New World scorpions from the Miocene that are rarely found trapped in amber. PMID:26244974

  18. Game theory model of traffic participants within amber time at signalized intersection.

    PubMed

    Qi, Weiwei; Wen, Huiying; Fu, Chuanyun; Song, Mo

    2014-01-01

    The traffic light scheme is composed of red, green, and amber lights, and it has been defined clearly for the traffic access of red and green lights; however, the definition of that for the amber light is indistinct, which leads to the appearance of uncertainty factors and serious traffic conflicts during the amber light. At present, the traffic administrations are faced with the decision of whether to forbid passing or not during the amber light in the cities of China. On one hand, it will go against the purpose of setting amber lights if forbidding passing; on the other hand, it may lead to a mess of traffic flow running if not. And meanwhile the drivers are faced with the decision of passing the intersection or stopping during the amber light as well. So the decision-making behavior of traffic administrations and drivers can be converted into a double game model. And through quantification of their earnings in different choice conditions, the optimum decision-making plan under specific conditions could be solved via the Nash equilibrium solution concept. Thus the results will provide a basis for the formulation of the traffic management strategy. PMID:25580108

  19. Game Theory Model of Traffic Participants within Amber Time at Signalized Intersection

    PubMed Central

    Qi, Weiwei; Wen, Huiying; Fu, Chuanyun; Song, Mo

    2014-01-01

    The traffic light scheme is composed of red, green, and amber lights, and it has been defined clearly for the traffic access of red and green lights; however, the definition of that for the amber light is indistinct, which leads to the appearance of uncertainty factors and serious traffic conflicts during the amber light. At present, the traffic administrations are faced with the decision of whether to forbid passing or not during the amber light in the cities of China. On one hand, it will go against the purpose of setting amber lights if forbidding passing; on the other hand, it may lead to a mess of traffic flow running if not. And meanwhile the drivers are faced with the decision of passing the intersection or stopping during the amber light as well. So the decision-making behavior of traffic administrations and drivers can be converted into a double game model. And through quantification of their earnings in different choice conditions, the optimum decision-making plan under specific conditions could be solved via the Nash equilibrium solution concept. Thus the results will provide a basis for the formulation of the traffic management strategy. PMID:25580108

  20. Terpenoid Compositions and Botanical Origins of Late Cretaceous and Miocene Amber from China

    PubMed Central

    Shi, Gongle; Dutta, Suryendu; Paul, Swagata; Wang, Bo; Jacques, Frédéric M. B.

    2014-01-01

    The terpenoid compositions of the Late Cretaceous Xixia amber from Central China and the middle Miocene Zhangpu amber from Southeast China were analyzed by gas chromatography-mass spectrometry (GC-MS) to elucidate their botanical origins. The Xixia amber is characterized by sesquiterpenoids, abietane and phyllocladane type diterpenoids, but lacks phenolic abietanes and labdane derivatives. The molecular compositions indicate that the Xixia amber is most likely contributed by the conifer family Araucariaceae, which is today distributed primarily in the Southern Hemisphere, but widely occurred in the Northern Hemisphere during the Mesozoic according to paleobotanical evidence. The middle Miocene Zhangpu amber is characterized by amyrin and amyrone-based triterpenoids and cadalene-based sesquiterpenoids. It is considered derived from the tropical angiosperm family Dipterocarpaceae based on these compounds and the co-occurring fossil winged fruits of the family in Zhangpu. This provides new evidence for the occurrence of a dipterocarp forest in the middle Miocene of Southeast China. It is the first detailed biomarker study for amber from East Asia. PMID:25354364

  1. Insect outbreaks produce distinctive carbon isotope signatures in defensive resins and fossiliferous ambers

    PubMed Central

    McKellar, Ryan C.; Wolfe, Alexander P.; Muehlenbachs, Karlis; Tappert, Ralf; Engel, Michael S.; Cheng, Tao; Sánchez-Azofeifa, G. Arturo

    2011-01-01

    Despite centuries of research addressing amber and its various inclusions, relatively little is known about the specific events having stimulated the production of geologically relevant volumes of plant resin, ultimately yielding amber deposits. Although numerous hypotheses have invoked the role of insects, to date these have proven difficult to test. Here, we use the current mountain pine beetle outbreak in western Canada as an analogy for the effects of infestation on the stable isotopic composition of carbon in resins. We show that infestation results in a rapid (approx. 1 year) 13C enrichment of fresh lodgepole pine resins, in a pattern directly comparable with that observed in resins collected from uninfested trees subjected to water stress. Furthermore, resin isotopic values are shown to track both the progression of infestation and instances of recovery. These findings can be extended to fossil resins, including Miocene amber from the Dominican Republic and Late Cretaceous New Jersey amber, revealing similar carbon-isotopic patterns between visually clean ambers and those associated with the attack of wood-boring insects. Plant exudate δ13C values constitute a sensitive monitor of ecological stress in both modern and ancient forest ecosystems, and provide considerable insight concerning the genesis of amber in the geological record. PMID:21429925

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

    PubMed Central

    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

  3. Unique Temporal and Spatial Biomolecular Emission Profile on Individual Zinc Oxide Nanorods

    PubMed Central

    Singh, Manpreet; Song, Sheng; Hahm, Jong-in

    2013-01-01

    Zinc oxide nanorods (ZnO NRs) have emerged in recent years as extremely useful, optical signal-enhancing platforms in DNA and protein detection. Although the use of ZnO NRs in biodetection has been demonstrated so far in systems involving many ZnO NRs per detection element, their future applications will likely take place in a miniaturized setting while exploiting single ZnO NRs in a low-volume, high-throughput bioanalysis. In this paper, we investigate temporal and spatial characteristics of biomolecular fluorescence on individual ZnO NR systems. Quantitative and qualitative examinations of biomolecular intensity and photostability are carried out as a function of two important criteria, time and position along the long axis (length) of NRs. Photostability profiles are also measured with respect to the position on NRs and compared to those characteristics of biomolecules on polymeric control platforms. Unlike uniformly distributed signal observed on the control platforms, both fluorescence intensity and photostability are position-dependent on individual ZnO NRs. We have identified a unique phenomenon of highly localized, fluorescence intensification on the nanorod ends (FINE) of well-characterized, individual ZnO nanostructures. When compared to the polymeric controls, biomolecular fluorescence intensity and photostability are determined to be higher on individual ZnO NRs regardless of the position on NRs. We have also carried out finite-difference time-domain simulations whose results agree well with the observed FINE. The outcomes of our investigation will offer a much needed basis for signal interpretation for biodetection devices and platforms consisting of single ZnO NRs and, at the same time, contribute significantly to provide insight in understanding biomolecular fluorescence observed from ZnO NR ensemble-based systems. PMID:24193145

  4. Biomolecular surface construction by PDE transform.

    PubMed

    Zheng, Qiong; Yang, Siyang; Wei, Guo-Wei

    2012-03-01

    This work proposes a new framework for the surface generation based on the partial differential equation (PDE) transform. The PDE transform has recently been introduced as a general approach for the mode decomposition of images, signals, and data. It relies on the use of arbitrarily high-order PDEs to achieve the time-frequency localization, control the spectral distribution, and regulate the spatial resolution. The present work provides a new variational derivation of high-order PDE transforms. The fast Fourier transform is utilized to accomplish the PDE transform so as to avoid stringent stability constraints in solving high-order PDEs. As a consequence, the time integration of high-order PDEs can be done efficiently with the fast Fourier transform. The present approach is validated with a variety of test examples in two-dimensional and three-dimensional settings. We explore the impact of the PDE transform parameters, such as the PDE order and propagation time, on the quality of resulting surfaces. Additionally, we utilize a set of 10 proteins to compare the computational efficiency of the present surface generation method and a standard approach in Cartesian meshes. Moreover, we analyze the present method by examining some benchmark indicators of biomolecular surface, that is, surface area, surface-enclosed volume, solvation free energy, and surface electrostatic potential. A test set of 13 protein molecules is used in the present investigation. The electrostatic analysis is carried out via the Poisson-Boltzmann equation model. To further demonstrate the utility of the present PDE transform-based surface method, we solve the Poisson-Nernst-Planck equations with a PDE transform surface of a protein. Second-order convergence is observed for the electrostatic potential and concentrations. Finally, to test the capability and efficiency of the present PDE transform-based surface generation method, we apply it to the construction of an excessively large biomolecule, a

  5. An improved generalized AMBER force field (GAFF) for urea.

    PubMed

    Ozpinar, Gül Altinbaş; Peukert, Wolfgang; Clark, Timothy

    2010-09-01

    We describe an improved force field parameter set for the generalized AMBER force field (GAFF) for urea. Quantum chemical computations were used to obtain geometrical and energetic parameters of urea dimers and larger oligomers using AM1 semiempirical MO theory, density functional theory at the B3LYP/6-31G(d,p) level, MP2 and CCSD ab initio calculations with the 6-311++G(d,p), aug-cc-pVDZ, aug-cc-pVTZ, and aug-cc-pVQZ basis sets, and with the CBS-QB3 and CBS-APNO complete basis set methods. Seven different urea dimer structures were optimized at the MP2/aug-cc-pVDZ level to obtain accurate interaction energies. Atomic partial charges were calculated at the MP2/aug-cc-pVDZ level with the restrained electrostatic potential (RESP) fitting approach. The interaction energies computed with these new RESP charges in the force field are consistent with those obtained from CCSD and MP2 calculations. The linear dimer structure calculated using the force field with modified geometrical parameters and the new RESP charge set agrees well with available experimental data. PMID:20162312

  6. Extension of the AMBER molecular dynamics software to Intel's Many Integrated Core (MIC) architecture

    NASA Astrophysics Data System (ADS)

    Needham, Perri J.; Bhuiyan, Ashraf; Walker, Ross C.

    2016-04-01

    We present an implementation of explicit solvent particle mesh Ewald (PME) classical molecular dynamics (MD) within the PMEMD molecular dynamics engine, that forms part of the AMBER v14 MD software package, that makes use of Intel Xeon Phi coprocessors by offloading portions of the PME direct summation and neighbor list build to the coprocessor. We refer to this implementation as pmemd MIC offload and in this paper present the technical details of the algorithm, including basic models for MPI and OpenMP configuration, and analyze the resultant performance. The algorithm provides the best performance improvement for large systems (>400,000 atoms), achieving a ∼35% performance improvement for satellite tobacco mosaic virus (1,067,095 atoms) when 2 Intel E5-2697 v2 processors (2 ×12 cores, 30M cache, 2.7 GHz) are coupled to an Intel Xeon Phi coprocessor (Model 7120P-1.238/1.333 GHz, 61 cores). The implementation utilizes a two-fold decomposition strategy: spatial decomposition using an MPI library and thread-based decomposition using OpenMP. We also present compiler optimization settings that improve the performance on Intel Xeon processors, while retaining simulation accuracy.

  7. Mechanism of flow-induced biomolecular and colloidal aggregate breakup

    NASA Astrophysics Data System (ADS)

    Conchúir, Breanndán Ó.; Zaccone, Alessio

    2013-03-01

    The drift-diffusion equation is first solved analytically for the dissociation rate and lifetime of a biomolecular or colloidal dimer bonded by realistic intermolecular potentials, under shear flow. Then we show using rigidity percolation concepts that the lifetime of a generic cluster formed under shear is controlled by the typical lifetime of a single bond in its interior. The latter, however, is also affected by collective stress transmission from other bonds in the aggregate, which we account for by introducing a semiempirical, analytical stress transmission efficiency 0⩽Γ⩽1 calibrated on several simulation data sets. We show that aggregate breakup is a thermally activated process in which the activation energy is controlled by the interplay between intermolecular forces and the shear drift. The collective contribution to the overall shear drift term is dominant for large enough fractal aggregates, while surface erosion prevails for small and compact aggregates. The crossover between the two regimes occurs when ΓN≃2, where both the number of particles in the cluster N and the stress transmission efficiency Γ depend on the aggregate structure through the fractal dimension df. The analytical framework for the aggregate breakup rate is in quantitative agreement with experiments and can be used in future studies in the population balance modeling of colloidal and protein aggregation.

  8. Integrated Spintronic Platforms for Biomolecular Recognition Detection

    NASA Astrophysics Data System (ADS)

    Martins, V. C.; Cardoso, F. A.; Loureiro, J.; Mercier, M.; Germano, J.; Cardoso, S.; Ferreira, R.; Fonseca, L. P.; Sousa, L.; Piedade, M. S.; Freitas, P. P.

    2008-06-01

    This paper covers recent developments in magnetoresistive based biochip platforms fabricated at INESC-MN, and their application to the detection and quantification of pathogenic waterborn microorganisms in water samples for human consumption. Such platforms are intended to give response to the increasing concern related to microbial contaminated water sources. The presented results concern the development of biological active DNA chips and protein chips and the demonstration of the detection capability of the present platforms. Two platforms are described, one including spintronic sensors only (spin-valve based or magnetic tunnel junction based), and the other, a fully scalable platform where each probe site consists of a MTJ in series with a thin film diode (TFD). Two microfluidic systems are described, for cell separation and concentration, and finally, the read out and control integrated electronics are described, allowing the realization of bioassays with a portable point of care unit. The present platforms already allow the detection of complementary biomolecular target recognition with 1 pM concentration.

  9. Microwave spectroscopy of biomolecular building blocks.

    PubMed

    Alonso, José L; López, Juan C

    2015-01-01

    Microwave spectroscopy, considered as the most definitive gas phase structural probe, is able to distinguish between different conformational structures of a molecule, because they have unique spectroscopic constants and give rise to distinct individual rotational spectra.Previously, application of this technique was limited to molecular specimens possessing appreciable vapor pressures, thus discarding the possibility of studying many other molecules of biological importance, in particular those with high melting points, which had a tendency to undergo thermal reactions, and ultimately degradation, upon heating.Nowadays, the combination of laser ablation with Fourier transform microwave spectroscopy techniques, in supersonic jets, has enabled the gas-phase study of such systems. In this chapter, these techniques, including broadband spectroscopy, as well as results of their application into the study of the conformational panorama and structure of biomolecular building blocks, such as amino acids, nucleic bases, and monosaccharides, are briefly discussed, and with them, the tools for conformational assignation - rotational constants, nuclear quadrupole coupling interaction, and dipole moment. PMID:25721775

  10. NMR Studies of Dynamic Biomolecular Conformational Ensembles

    PubMed Central

    Torchia, Dennis A.

    2015-01-01

    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. PMID:25669739

  11. Fossil mesostigmatid mites (Mesostigmata: Gamasina, Microgyniina, Uropodina), associated with longhorn beetles (Coleoptera: Cerambycidae) in Baltic amber

    NASA Astrophysics Data System (ADS)

    Dunlop, Jason A.; Kontschán, Jenő; Zwanzig, Michael

    2013-04-01

    Fossil mesostigmatid mites are extremely rare. Inclusions assignable to the tortoise mites (Mesostigmata, Uropodina) are described here for the first time from Eocene (ca. 44-49 Ma) Baltic amber. This is the oldest record of Uropodina and documents the first unequivocal amber examples potentially assignable to the extant genus Uroobovella Berlese, 1903 (Uropodoidea: Urodinychidae). Further mites in the same amber pieces are tentatively assigned to Microgynioidea (Microgyniina) and Ascidae (Gamasina), both potentially representing the oldest records of their respective superfamily and family groups. This new material also preserves behavioural ecology in the form of phoretic deutonymphs attached to their carriers via a characteristic anal pedicel. These deutonymphs in amber are intimately associated with longhorn beetles (Coleoptera: Cerambycidae), probably belonging to the extinct species Nothorhina granulicollis Zang, 1905. Modern uropodines have been recorded phoretic on species belonging to several beetle families, including records of living Uroobovella spp. occurring on longhorn beetles. Through these amber inclusions, a uropodine-cerambycid association can now be dated back to at least the Eocene.

  12. Deuterium isotopic exchangeability of resin and amber at low thermal stress under hydrous conditions

    NASA Astrophysics Data System (ADS)

    Gonzalez, G.; Tappert, R.; Wolfe, A. P.; Muehlenbachs, K.

    2012-04-01

    Hydrous deuterium-exchange experiments have shown that a significant fraction of the original D/H composition of bulk kerogens, bitumens and expelled oils may participate in isotopic exchange reactions during burial diagenesis. However, it is unknown to what extent plant-derived secondary metabolites, namely resins and their fossil counterpart amber, exchange hydrogen isotopes following their biosynthesis. This situation hinders the application of resin D/H measurements in paleoenvironmental reconstruction. Here, we assess explicitly hydrogen exchange in resins and ambers using a series of immersion experiments in deuterated (D-enriched) waters over a period of several months at several temperatures. We are especially interested in assessing whether significant H-isotopic exchange occurs between resins and meteoric waters during early thermal maturation and polymerization. At 90°C, equivalent to ~3km of burial in most diagenetic regimes, modern conifer and angiosperm resins have an average post-metabolic H exchange of 4.6%, compared to only 1.1% for mature, polymerized ambers. At 55°C the degree of exchange is considerably lower: 1.9% for resins and 0.6% for ambers. These results indicate that most D/H isotopic exchange occurs prior to polymerization reactions, thereby confirming that D/H measurements from amber constitute a potentially sensitive proxy for environmental change.

  13. Biomolecular dynamics: order-disorder transitions and energy landscapes.

    PubMed

    Whitford, Paul C; Sanbonmatsu, Karissa Y; Onuchic, José N

    2012-07-01

    While the energy landscape theory of protein folding is now a widely accepted view for understanding how relatively weak molecular interactions lead to rapid and cooperative protein folding, such a framework must be extended to describe the large-scale functional motions observed in molecular machines. In this review, we discuss (1) the development of the energy landscape theory of biomolecular folding, (2) recent advances toward establishing a consistent understanding of folding and function and (3) emerging themes in the functional motions of enzymes, biomolecular motors and other biomolecular machines. Recent theoretical, computational and experimental lines of investigation have provided a very dynamic picture of biomolecular motion. In contrast to earlier ideas, where molecular machines were thought to function similarly to macroscopic machines, with rigid components that move along a few degrees of freedom in a deterministic fashion, biomolecular complexes are only marginally stable. Since the stabilizing contribution of each atomic interaction is on the order of the thermal fluctuations in solution, the rigid body description of molecular function must be revisited. An emerging theme is that functional motions encompass order-disorder transitions and structural flexibility provides significant contributions to the free energy. In this review, we describe the biological importance of order-disorder transitions and discuss the statistical-mechanical foundation of theoretical approaches that can characterize such transitions. PMID:22790780

  14. Biomolecular Dynamics: Order-Disorder Transitions and Energy Landscapes

    PubMed Central

    Whitford, Paul C.; Sanbonmatsu, Karissa Y.; Onuchic, José N.

    2013-01-01

    While the energy landscape theory of protein folding is now a widely accepted view for understanding how relatively-weak molecular interactions lead to rapid and cooperative protein folding, such a framework must be extended to describe the large-scale functional motions observed in molecular machines. In this review, we discuss 1) the development of the energy landscape theory of biomolecular folding, 2) recent advances towards establishing a consistent understanding of folding and function, and 3) emerging themes in the functional motions of enzymes, biomolecular motors, and other biomolecular machines. Recent theoretical, computational, and experimental lines of investigation are providing a very dynamic picture of biomolecular motion. In contrast to earlier ideas, where molecular machines were thought to function similarly to macroscopic machines, with rigid components that move along a few degrees of freedom in a deterministic fashion, biomolecular complexes are only marginally stable. Since the stabilizing contribution of each atomic interaction is on the order of the thermal fluctuations in solution, the rigid body description of molecular function must be revisited. An emerging theme is that functional motions encompass order-disorder transitions and structural flexibility provide significant contributions to the free-energy. In this review, we describe the biological importance of order-disorder transitions and discuss the statistical-mechanical foundation of theoretical approaches that can characterize such transitions. PMID:22790780

  15. Biomolecular Modification of Inorganic Crystal Growth

    SciTech Connect

    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

  16. Microfluidic Devices for Studying Biomolecular Interactions

    NASA Technical Reports Server (NTRS)

    Wilson, Wilbur W.; Garcia, Carlos d.; Henry, Charles S.

    2006-01-01

    Microfluidic devices for monitoring biomolecular interactions have been invented. These devices are basically highly miniaturized liquid-chromatography columns. They are intended to be prototypes of miniature analytical devices of the laboratory on a chip type that could be fabricated rapidly and inexpensively and that, because of their small sizes, would yield analytical results from very small amounts of expensive analytes (typically, proteins). Other advantages to be gained by this scaling down of liquid-chromatography columns may include increases in resolution and speed, decreases in the consumption of reagents, and the possibility of performing multiple simultaneous and highly integrated analyses by use of multiple devices of this type, each possibly containing multiple parallel analytical microchannels. The principle of operation is the same as that of a macroscopic liquid-chromatography column: The column is a channel packed with particles, upon which are immobilized molecules of the protein of interest (or one of the proteins of interest if there are more than one). Starting at a known time, a solution or suspension containing molecules of the protein or other substance of interest is pumped into the channel at its inlet. The liquid emerging from the outlet of the channel is monitored to detect the molecules of the dissolved or suspended substance(s). The time that it takes these molecules to flow from the inlet to the outlet is a measure of the degree of interaction between the immobilized and the dissolved or suspended molecules. Depending on the precise natures of the molecules, this measure can be used for diverse purposes: examples include screening for solution conditions that favor crystallization of proteins, screening for interactions between drugs and proteins, and determining the functions of biomolecules.

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

    PubMed Central

    Shapiro, Ehud

    2012-01-01

    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. PMID:22649583

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

    PubMed

    Shapiro, Ehud

    2012-08-01

    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. PMID:22649583

  19. CRISPRi-Manipulation of Genetic Code Expansion via RF1 for Reassignment of Amber Codon in Bacteria

    PubMed Central

    Zhang, Bo; Yang, Qi; Chen, Jingxian; Wu, Ling; Yao, Tianzhuo; Wu, Yiming; Xu, Huan; Zhang, Lihe; Xia, Qing; Zhou, Demin

    2016-01-01

    The precise engineering of proteins in bacteria via the amber codon has been hampered by the poor incorporation of unnatural amino acid (UAA). Here we explored the amber assignment as a sense codon for UAA by CRISPRi targeting release factor 1 (RF1). Scanning of RF1 gene with sgRNAs identified target loci that differentiate RF1 repressions. Quantitation of RF1 repressions versus UAA incorporation indicated an increasing interrelation with the amber reassignment maximized upon RF1 knockdown to ~30%, disclosing the beneficial role of RF1 in amber assignment. However, further RF1 repression reversed this trend resulting from the detrimental effects on host cell growth, disclosing the harmful aspect of RF1 in reassignment of the amber codon. Our data indicate RF1 as a switch manipulating genetic code expansion and pave a direction via CRISPRi for precise engineering and efficient production of proteins in bacteria. PMID:26818534

  20. Revival and Identification of Bacterial Spores in 25- to 40-Million-Year-Old Dominican Amber

    NASA Astrophysics Data System (ADS)

    Cano, Raul J.; Borucki, Monica K.

    1995-05-01

    A bacterial spore was revived, cultured, and identified from the abdominal contents of extinct bees preserved for 25 to 40 million years in buried Dominican amber. Rigorous surface decontamination of the amber and aseptic procedures were used during the recovery of the bacterium. Several lines of evidence indicated that the isolated bacterium was of ancient origin and not an extant contaminant. The characteristic enzymatic, biochemical, and 16S ribosomal DNA profiles indicated that the ancient bacterium is most closely related to extant Bacillus sphaericus.

  1. Electrically driven green, olivine, and amber color nanopyramid light emitting diodes.

    PubMed

    Chang, Shih-Pang; Chang, Jet-Rung; Sou, Kuok-Pan; Liu, Mei-Chun; Cheng, Yuh-Jen; Kuo, Hao-Chung; Chang, Chun-Yen

    2013-10-01

    We report the fabrication and studies of electrically driven green, olivine, and amber color nanopyramid GaN light emitting diodes (LEDs). InGaN/GaN multiple quantum wells (MQWs) were grown on the nanopyramid semipolar facets. Compared with the commonly used (0001) c-plane MQWs, the semipolar facet has lower piezoelectric field, resulting in much faster radiative recombination efficiency. This is important for high In content MQWs. The measured internal quantum efficiencies for green, olivine, and amber color LED are 30%, 25%, and 21%, respectively. The radiative and non-radiative lifetime of the semipolar MQWs are also investigated. PMID:24104218

  2. Ancient Ephemeroptera–Collembola Symbiosis Fossilized in Amber Predicts Contemporary Phoretic Associations

    PubMed Central

    Penney, David; McNeil, Andrew; Green, David I.; Bradley, Robert S.; Jepson, James E.; Withers, Philip J.; Preziosi, Richard F.

    2012-01-01

    X-ray computed tomography is used to identify a unique example of fossilized phoresy in 16 million-year-old Miocene Dominican amber involving a springtail being transported by a mayfly. It represents the first evidence (fossil or extant) of phoresy in adult Ephemeroptera and only the second record in Collembola (the first is also preserved in amber). This is the first record of Collembola using winged insects for dispersal. This fossil predicts the occurrence of similar behaviour in living springtails and helps explain the global distribution of Collembola today. PMID:23082186

  3. First Record of Anisoptera (Insecta: Odonata) from mid-Cretaceous Burmese Amber.

    PubMed

    Schädel, Mario; Bechly, Günter

    2016-01-01

    The fossil dragonfly Burmalindenia imperfecta gen. et sp. nov. is described from mid-Cretaceous Burmese amber as the first record of the odonate suborder Anisoptera for this locality and one of the few records from amber in general. The inclusion comprises two fragments of the two hind wings of a dragonfly. The fossil can be attributed to a new genus and species of the family Gomphidae, presumably in the subfamily Lindeniinae, and features a strange teratological phenomenon in its wing venation. PMID:27394756

  4. Cantilever arrays for multiplexed mechanical analysis of biomolecular reactions.

    PubMed

    Yue, Min; Stachowiak, Jeanne C; Majumdar, Arunava

    2004-09-01

    Microchips containing arrays of cantilever beams have been used to mechanically detect and quantitatively analyze multiple reactions of DNA hybridization and antigen-antibody binding simultaneously. The reaction-induced deflection of a cantilever beam reflects the interplay between strain energy increase of the beam and the free energy reduction of a reaction, providing an ideal tool for investigating the connection between mechanics and chemistry of biomolecular reactions. Since free energy reduction is common for all reactions, the cantilever array forms a universal platform for label-free detection of various specific biomolecular reactions. A few such reactions and their implications in biology and biotechnology are discussed. PMID:16783934

  5. Comparing the catalytic strategy of ATP hydrolysis in biomolecular motors.

    PubMed

    Kiani, Farooq Ahmad; Fischer, Stefan

    2016-07-27

    ATP-driven biomolecular motors utilize the chemical energy obtained from the ATP hydrolysis to perform vital tasks in living cells. Understanding the mechanism of enzyme-catalyzed ATP hydrolysis reaction has substantially progressed lately thanks to combined quantum/classical molecular mechanics (QM/MM) simulations. Here, we present a comparative summary of the most recent QM/MM results for myosin, kinesin and F1-ATPase motors. These completely different motors achieve the acceleration of ATP hydrolysis through a very similar catalytic mechanism. ATP hydrolysis has high activation energy because it involves the breaking of two strong bonds, namely the Pγ-Oβγ bond of ATP and the H-O bond of lytic water. The key to the four-fold decrease in the activation barrier by the three enzymes is that the breaking of the Pγ-Oβγ bond precedes the deprotonation of the lytic water molecule, generating a metaphosphate hydrate complex. The resulting singly charged trigonal planar PγO3(-) metaphosphate is a better electrophilic target for attack by an OaH(-) hydroxyl group. The formation of this OaH(-) is promoted by a strong polarization of the lytic water: in all three proteins, this water is forming a hydrogen-bond with a backbone carbonyl group and interacts with the carboxylate group of glutamate (either directly or via an intercalated water molecule). This favors the shedding of one proton by the attacking water. The abstracted proton is transferred to the γ-phosphate via various proton wires, resulting in a H2PγO4(-)/ADP(3-) product state. This catalytic strategy is so effective that most other nucleotide hydrolyzing enzymes adopt a similar approach, as suggested by their very similar triphosphate binding sites. PMID:27296627

  6. Perspective: Watching low-frequency vibrations of water in biomolecular recognition by THz spectroscopy

    NASA Astrophysics Data System (ADS)

    Xu, Yao; Havenith, Martina

    2015-11-01

    Terahertz (THz) spectroscopy has turned out to be a powerful tool which is able to shed new light on the role of water in biomolecular processes. The low frequency spectrum of the solvated biomolecule in combination with MD simulations provides deep insights into the collective hydrogen bond dynamics on the sub-ps time scale. The absorption spectrum between 1 THz and 10 THz of solvated biomolecules is sensitive to changes in the fast fluctuations of the water network. Systematic studies on mutants of antifreeze proteins indicate a direct correlation between biological activity and a retardation of the (sub)-ps hydration dynamics at the protein binding site, i.e., a "hydration funnel." Kinetic THz absorption studies probe the temporal changes of THz absorption during a biological process, and give access to the kinetics of the coupled protein-hydration dynamics. When combined with simulations, the observed results can be explained in terms of a two-tier model involving a local binding and a long range influence on the hydration bond dynamics of the water around the binding site that highlights the significance of the changes in the hydration dynamics at recognition site for biomolecular recognition. Water is shown to assist molecular recognition processes.

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

    PubMed Central

    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

  8. The universal statistical distributions of the affinity, equilibrium constants, kinetics and specificity in biomolecular recognition.

    PubMed

    Zheng, Xiliang; Wang, Jin

    2015-04-01

    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

  9. Biomolecular ion detection using high-temperature superconducting MgB2 strips

    NASA Astrophysics Data System (ADS)

    Zen, N.; Shibata, H.; Mawatari, Y.; Koike, M.; Ohkubo, M.

    2015-06-01

    Superconducting strip ion detectors (SSIDs) are promising for realization of ideal ion detection with 100% efficiency and nanosecond-scale time response in time-of-flight mass spectrometry. We have detected single biomolecular ions in the keV range using a 10-nm-thick and 250-nm-wide strip of a high temperature superconductor, magnesium diboride (MgB2), at temperatures of up to 13 K. The output pulse shape is explained remarkably well using circuit simulations and time-dependent Ginzburg-Landau simulations coupled with a heat diffusion equation. The simulations show that the hot spot model is applicable to the proposed MgB2-SSIDs and the normal region expansion is completed within 16 ps, which corresponds to a maximum length of 1010 nm.

  10. Biogeographic and evolutionary implications of a diverse paleobiota in amber from the early Eocene of India

    PubMed Central

    Rust, Jes; Singh, Hukam; Rana, Rajendra S.; McCann, Tom; Singh, Lacham; Anderson, Ken; Sarkar, Nivedita; Nascimbene, Paul C.; Stebner, Frauke; Thomas, Jennifer C.; Solórzano Kraemer, Monica; Williams, Christopher J.; Engel, Michael S.; Sahni, Ashok; Grimaldi, David

    2010-01-01

    For nearly 100 million years, the India subcontinent drifted from Gondwana until its collision with Asia some 50 Ma, during which time the landmass presumably evolved a highly endemic biota. Recent excavations of rich outcrops of 50–52-million-year-old amber with diverse inclusions from the Cambay Shale of Gujarat, western India address this issue. Cambay amber occurs in lignitic and muddy sediments concentrated by near-shore chenier systems; its chemistry and the anatomy of associated fossil wood indicates a definitive source of Dipterocarpaceae. The amber is very partially polymerized and readily dissolves in organic solvents, thus allowing extraction of whole insects whose cuticle retains microscopic fidelity. Fourteen orders and more than 55 families and 100 species of arthropod inclusions have been discovered thus far, which have affinities to taxa from the Eocene of northern Europe, to the Recent of Australasia, and the Miocene to Recent of tropical America. Thus, India just prior to or immediately following contact shows little biological insularity. A significant diversity of eusocial insects are fossilized, including corbiculate bees, rhinotermitid termites, and modern subfamilies of ants (Formicidae), groups that apparently radiated during the contemporaneous Early Eocene Climatic Optimum or just prior to it during the Paleocene-Eocene Thermal Maximum. Cambay amber preserves a uniquely diverse and early biota of a modern-type of broad-leaf tropical forest, revealing 50 Ma of stasis and change in biological communities of the dipterocarp primary forests that dominate southeastern Asia today. PMID:20974929

  11. A remarkable new pygmy grasshopper (Orthoptera, Tetrigidae) in Miocene amber from the Dominican Republic

    PubMed Central

    Heads, Sam W.; Thomas, M. Jared; Wang, Yinan

    2014-01-01

    Abstract A new genus and species of pygmy grasshopper (Orthoptera: Tetrigidae) is described from Early Miocene (Burdigalian) Dominican amber. Electrotettix attenboroughi Heads & Thomas, gen. et sp. n. is assigned to the subfamily Cladonotinae based on the deeply forked frontal costa, but is remarkable for the presence of tegmina and hind wings, hitherto unknown in this subfamily. PMID:25147472

  12. New predatory cockroaches (Insecta: Blattaria: Manipulatoridae fam.n.) from the Upper Cretaceous Myanmar amber

    NASA Astrophysics Data System (ADS)

    Vršanský, Peter; Bechly, Günter

    2015-04-01

    We describe a new extinct lineage Manipulatoridae (new family) of cockroaches from the Upper Cretaceous (Cenomanian) amber of Myanmar. Manipulator modificaputis gen. et sp. n. is a morphologically unique extinct cockroach that represents the first (of a total of 29 known worldwide) cockroach family reported exclusively from the Myanmar amber. This family represents an early side branch of the stem group of Mantodea (most probably a sister group of Eadiidae within Blattaria/Corydioidea) because it has some synapomorphies with the Mantodea (including the stem group and Eadiidae). This family also retains symplesiomorphies that exclude a position in the crown group, and furthermore has unique autapomorphies that exclude a position as a direct ancestor of Mantodea. The unique adaptations such as strongly elongated extremities and freely movable head on a long neck suggest that these animals were pursuit predators. Five additional specimens (including two immatures) reported from the Myanmar amber suggest that this group was relatively rare but belonged to the indigenous and autochthonous inhabitants of the ancient amber forest of the Myanmar region.

  13. A swarm of whiteflies--the first record of gregarious behavior from Eocene Baltic amber.

    PubMed

    Szwedo, Jacek; Drohojowska, Jowita

    2016-04-01

    A new whitefly Snotra christelae gen. et sp. n. is characterized, illustrated, and described from the Baltic amber. It represents the first record of gregarious behavior of Aleyrodinae (Aleyrodidae) whiteflies in fossil state. Implications of this finding on interpretation of whiteflies and their host-plant relationships and evolutionary traits of the group are discussed. PMID:27023734

  14. A swarm of whiteflies—the first record of gregarious behavior from Eocene Baltic amber

    NASA Astrophysics Data System (ADS)

    Szwedo, Jacek; Drohojowska, Jowita

    2016-04-01

    A new whitefly Snotra christelae gen. et sp. n. is characterized, illustrated, and described from the Baltic amber. It represents the first record of gregarious behavior of Aleyrodinae (Aleyrodidae) whiteflies in fossil state. Implications of this finding on interpretation of whiteflies and their host-plant relationships and evolutionary traits of the group are discussed.

  15. The oldest psyllipsocid booklice, in Lower Cretaceous amber from Lebanon (Psocodea, Trogiomorpha, Psocathropetae, Psyllipsocidae)

    PubMed Central

    Azar, Dany; Nel, André

    2011-01-01

    Abstract Libanopsyllipsocus alexanderasnitsyni gen. et sp. n., of Psyllipsocidae is described and figured from the Lower Cretaceous amber of Lebanon. The position of the new taxon is discussed and the fossil is compared to other psyllipsocids. The species represents the earliest record of the family Psyllipsocidae. PMID:22259273

  16. Amino acid racemization in amber-entombed insects: implications for DNA preservation

    NASA Technical Reports Server (NTRS)

    Bada, J. L.; Wang, X. S.; Poinar, H. N.; Paabo, S.; Poinar, G. O.

    1994-01-01

    DNA depurination and amino acid racemization take place at similar rates in aqueous solution at neutral pH. This relationship suggests that amino acid racemization may be useful in accessing the extent of DNA chain breakage in ancient biological remains. To test this suggestion, we have investigated the amino acids in insects entombed in fossilized tree resins ranging in age from <100 years to 130 million years. The amino acids present in 40 to 130 million year old amber-entombed insects resemble those in a modern fly and are probably the most ancient, unaltered amino acids found so far on Earth. In comparison to other geochemical environments on the surface of the Earth, the amino acid racemization rate in amber insect inclusions is retarded by a factor of >10(4). These results suggest that in amber insect inclusions DNA depurination rates would also likely be retarded in comparison to aqueous solution measurements, and thus DNA fragments containing many hundreds of base pairs should be preserved. This conclusion is consistent with the reported successful retrieval of DNA sequences from amber-entombed organisms.

  17. 13C Solid State Nuclear Magnetic Resonance and µ-Raman Spectroscopic Characterization of Sicilian Amber.

    PubMed

    Barone, Germana; Capitani, Donatella; Mazzoleni, Paolo; Proietti, Noemi; Raneri, Simona; Longobardo, Ugo; Di Tullio, Valeria

    2016-08-01

    (13)C cross-polarization magic angle spinning (CPMAS) nuclear magnetic resonance (NMR) and µ-Raman spectroscopy were applied to characterize Sicilian amber samples. The main goal of this work was to supply a complete study of simetite, highlighting discriminating criteria useful to distinguish Sicilian amber from fossil resins from other regions and laying the foundations for building a spectroscopic database of Sicilian amber. With this aim, a private collection of unrefined simetite samples and fossil resins from the Baltic region and Dominican Republic was analyzed. Overall, the obtained spectra permitted simetite to be distinguished from the other resins. In addition, principal component analysis (PCA) was applied to the spectroscopic data, allowing the clustering of simetite samples with respect to the Baltic and Dominican samples and to group the simetite samples in two sets, depending on their maturity. Finally, the analysis of loadings allowed for a better understanding of the spectral features that mainly influenced the discriminating characteristics of the investigated ambers. PMID:27340217

  18. Story as a Bridge to Transformation: The Way beyond Death in Philip Pullman's "The Amber Spyglass."

    ERIC Educational Resources Information Center

    Lenz, Millicent

    2003-01-01

    Explains that in "The Amber Spyglass," Philip Pullman extends the psychological depth of literature for young readers by presenting in palpable terms a confrontation with death met by the human capacity for dealing creatively, through story, with personal mortality. Contends that Pullman's portrayal of the power of storytelling is placed within…

  19. Biogeographic and evolutionary implications of a diverse paleobiota in amber from the early Eocene of India.

    PubMed

    Rust, Jes; Singh, Hukam; Rana, Rajendra S; McCann, Tom; Singh, Lacham; Anderson, Ken; Sarkar, Nivedita; Nascimbene, Paul C; Stebner, Frauke; Thomas, Jennifer C; Solórzano Kraemer, Monica; Williams, Christopher J; Engel, Michael S; Sahni, Ashok; Grimaldi, David

    2010-10-26

    For nearly 100 million years, the India subcontinent drifted from Gondwana until its collision with Asia some 50 Ma, during which time the landmass presumably evolved a highly endemic biota. Recent excavations of rich outcrops of 50-52-million-year-old amber with diverse inclusions from the Cambay Shale of Gujarat, western India address this issue. Cambay amber occurs in lignitic and muddy sediments concentrated by near-shore chenier systems; its chemistry and the anatomy of associated fossil wood indicates a definitive source of Dipterocarpaceae. The amber is very partially polymerized and readily dissolves in organic solvents, thus allowing extraction of whole insects whose cuticle retains microscopic fidelity. Fourteen orders and more than 55 families and 100 species of arthropod inclusions have been discovered thus far, which have affinities to taxa from the Eocene of northern Europe, to the Recent of Australasia, and the Miocene to Recent of tropical America. Thus, India just prior to or immediately following contact shows little biological insularity. A significant diversity of eusocial insects are fossilized, including corbiculate bees, rhinotermitid termites, and modern subfamilies of ants (Formicidae), groups that apparently radiated during the contemporaneous Early Eocene Climatic Optimum or just prior to it during the Paleocene-Eocene Thermal Maximum. Cambay amber preserves a uniquely diverse and early biota of a modern-type of broad-leaf tropical forest, revealing 50 Ma of stasis and change in biological communities of the dipterocarp primary forests that dominate southeastern Asia today. PMID:20974929

  20. The oldest accurate record of Scenopinidae in the Lowermost Eocene amber of France (Diptera: Brachycera).

    PubMed

    Garrouste, Romain; Azar, Dany; Nel, Andre

    2016-01-01

    Eocenotrichia magnifica gen. et sp. nov. (Diptera: Scenopinidae: Metatrichini) is described and illustrated from the Lowermost Eocene amber of Oise (France) and represents the oldest definitive window fly fossil. The present discovery in the Earliest Eocene supports the Late Cretaceous-Paleocene age currently proposed for the emergence of Metatrichini. PMID:27394507

  1. Amber: Using "Tree Tears Turned to Stone" to Teach Biology, Ecology, and More!

    ERIC Educational Resources Information Center

    Clary, Renee M.; Wandersee, James H.

    2009-01-01

    Amber is a fossil by itself, and can also contain plants and animals that lived millions of years ago. Some of these perfectly preserved specimens give scientists a convenient window to past environments, including the biology, ecology, geology, and chemistry of Earth's past. By using an interdisciplinary approach, we can demonstrate to students a…

  2. A new species of Diochus from Baltic amber (Coleoptera, Staphylinidae, Diochini)

    PubMed Central

    Chatzimanolis, Stylianos; Engel, Michael S.

    2011-01-01

    Abstract The first fossil of the staphylinine tribe Diochini Casey is described and figured from an inclusion in mid-Eocene (Lutetian) Baltic amber. Diochus electrus sp. n. is distinguished from its congeners and the diversity of rove beetles (Staphylinidae s.l.) is summarized briefly. PMID:22144854

  3. Visualization of basal pleural space and lung with advanced multiple beam equalization radiography (AMBER).

    PubMed

    Aarts, N J; Oestmann, J W; Kool, L J

    1993-02-01

    During clinical use of AMBER (Advanced Multiple Beam Equalization Radiography) it was frequently felt that the basal lung and pleural space were better appreciated than with standard chest radiography. We aimed to quantify the amount of additional relevant anatomy seen in this part region and to review the normal radiographic anatomy. Four hundred patients without known chest disease were evaluated. Two groups of 200 patients (50% female) were studied with either AMBER or standard chest radiography (140 kVp, 180 cm FFD, Kodak Tmat G film, Lanex regular screen; for both techniques). Visualization of the pleural sinuses (in percent of the transverse thoracic diameter) and the basal pulmonary vessels (4-point scale) was evaluated by a panel of 3 radiologists. The shape of the sinus was traced if sufficiently visible and subjectively evaluated. A significantly (P < 0.05) larger segment of the dorsal (41 +/- 34%) and ventral (14 +/- 15%) sinuses was seen with the AMBER technique than with the standard technique (16 +/- 21% and 9 +/- 11%, respectively). Vessel visibility was also significantly (P < 0.001) better with AMBER (3.2 +/- 0.6) than with the standard technique (1.9 +/- 0.6). The dorsal sinus showed alternatively a curved or pointed configuration. PMID:8462578

  4. Transient response characteristics in a biomolecular integral controller.

    PubMed

    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. PMID:26997660

  5. Fast Analytical Methods for Macroscopic Electrostatic Models in Biomolecular Simulations*

    PubMed Central

    Xu, Zhenli; Cai, Wei

    2013-01-01

    We review recent developments of fast analytical methods for macroscopic electrostatic calculations in biological applications, including the Poisson–Boltzmann (PB) and the generalized Born models for electrostatic solvation energy. The focus is on analytical approaches for hybrid solvation models, especially the image charge method for a spherical cavity, and also the generalized Born theory as an approximation to the PB model. This review places much emphasis on the mathematical details behind these methods. PMID:23745011

  6. Biomolecular strategies for cell surface engineering

    NASA Astrophysics Data System (ADS)

    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 preliminary synopsis on amber scorpions with special reference to Burmite species: an extraordinary development of our knowledge in only 20 years.

    PubMed

    Lourenço, Wilson R

    2016-01-01

    A preliminary study on fossil scorpions found in amber, from the Lower Cretaceous through the Palaeocene and up to the Miocene is proposed. Scorpions remain rare among the arthropods found trapped in amber. Only 24 specimens are known from Cretaceous amber, representing eight families and subfamilies, ten genera and 21 species; in parallel, 10 specimens have been recorded from Baltic amber representing seven genera and ten species. A few more recent fossils from Dominican and Mexican amber have also been described. The present study of a new scorpion specimen from the Cretaceous amber of Myanmar (Burmite) resulted in the description of one new species, Betaburmesebuthus bellus sp. n. - belonging to the subfamily Palaeoburmesebuthinae Lourenço, 2015. The new description brings further elements to the clarification of the status of this subfamily, which is now raised to family level. Once again, this new Burmite element attests to the considerable degree of diversity in the Burmese amber-producing forests. PMID:27408601

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

    PubMed

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

    2015-10-01

    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. PMID:26378119

  9. Genetic and molecular analysis of eight tRNA(Trp) amber suppressors in Caenorhabditis elegans.

    PubMed

    Kondo, K; Makovec, B; Waterston, R H; Hodgkin, J

    1990-09-01

    Over 100 revertants of five different amber mutants were analyzed by Southern blot hybridization using synthetic oligomers as probes to detect a single base change at the anticodon, CCA to CTA (amber), of tRNA(Trp) genes of Caenohrabditis elegans. Of the 12 members of the tRNA(Trp) gene family, a total of eight were converted to amber suppressor alleles. All eight encode identical tRNAs; three of these are new tRNA(Trp) suppressors, sup-21, sup-33 and sup-34. Previous results had suggested that individual suppressor tRNA genes were expressed differentially in a cell-type- or developmental stage-specific manner. To extend these observations to the new genes and to test the specificity of expression against additional genes, cross suppression tests of these eight amber suppressors were carried out against amber mutations in several different genes including genes likely to be expressed in the same cell-type: three nervous system-affecting genes, two muscle structure-affecting genes and two genes presumed to be expressed in hypodermis. Seven out of eight suppressors could be distinguished one from another by the spectrum of their suppression efficiencies. These results also provide further evidence of cell-type-specific patterns of expression in the nervous system, muscle and hypodermis. The suppression pattern of the suppressor against the two muscle-affecting genes, unc-15 and unc-52, suggested that either the suppressors are expressed in a developmental stage-specific manner or that the unc-52 products are expressed in cell-types other than muscle, possibly hypodermis. PMID:2398498

  10. Output-input ratio in thermally fluctuating biomolecular machines

    NASA Astrophysics Data System (ADS)

    Kurzynski, Michal; Torchala, Mieczyslaw; Chelminiak, Przemyslaw

    2014-01-01

    Biological molecular machines are proteins that operate under isothermal conditions and hence are referred to as free energy transducers. They can be formally considered as enzymes that simultaneously catalyze two chemical reactions: the free energy-donating (input) reaction and the free energy-accepting (output) one. Most if not all biologically active proteins display a slow stochastic dynamics of transitions between a variety of conformational substates composing their native state. This makes the description of the enzymatic reaction kinetics in terms of conventional rate constants insufficient. In the steady state, upon taking advantage of the assumption that each reaction proceeds through a single pair (the gate) of transition conformational substates of the enzyme-substrates complex, the degree of coupling between the output and the input reaction fluxes has been expressed in terms of the mean first-passage times on a conformational transition network between the distinguished substates. The theory is confronted with the results of random-walk simulations on the five-dimensional hypercube. The formal proof is given that, for single input and output gates, the output-input degree of coupling cannot exceed unity. As some experiments suggest such exceeding, looking for the conditions for increasing the degree of coupling value over unity challenges the theory. Performed simulations of random walks on several model networks involving more extended gates indicate that the case of the degree of coupling value higher than 1 is realized in a natural way on critical branching trees extended by long-range shortcuts. Such networks are scale-free and display the property of the small world. For short-range shortcuts, the networks are scale-free and fractal, representing a reasonable model for biomolecular machines displaying tight coupling, i.e., the degree of coupling equal exactly to unity. A hypothesis is stated that the protein conformational transition networks, as

  11. The adaptive buffered force QM/MM method in the CP2K and AMBER software packages

    PubMed Central

    Mones, Letif; Jones, Andrew; Götz, Andreas W; Laino, Teodoro; Walker, Ross C; Leimkuhler, Ben; Csányi, Gábor; Bernstein, Noam

    2015-01-01

    The implementation and validation of the adaptive buffered force (AdBF) quantum-mechanics/molecular-mechanics (QM/MM) method in two popular packages, CP2K and AMBER are presented. The implementations build on the existing QM/MM functionality in each code, extending it to allow for redefinition of the QM and MM regions during the simulation and reducing QM-MM interface errors by discarding forces near the boundary according to the buffered force-mixing approach. New adaptive thermostats, needed by force-mixing methods, are also implemented. Different variants of the method are benchmarked by simulating the structure of bulk water, water autoprotolysis in the presence of zinc and dimethyl-phosphate hydrolysis using various semiempirical Hamiltonians and density functional theory as the QM model. It is shown that with suitable parameters, based on force convergence tests, the AdBF QM/MM scheme can provide an accurate approximation of the structure in the dynamical QM region matching the corresponding fully QM simulations, as well as reproducing the correct energetics in all cases. Adaptive unbuffered force-mixing and adaptive conventional QM/MM methods also provide reasonable results for some systems, but are more likely to suffer from instabilities and inaccuracies. © 2015 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. PMID:25649827

  12. X3DBio2: A visual analysis tool for biomolecular structure comparison

    NASA Astrophysics Data System (ADS)

    Yi, Hong; Thakur, Sidharth; Sethaphong, Latsavongsakda; Yingling, Yaroslava G.

    2013-01-01

    A major problem in structural biology is the recognition of differences and similarities between related three dimensional (3D) biomolecular structures. Investigating these structure relationships is important not only for understanding of functional properties of biologically significant molecules, but also for development of new and improved materials based on naturally-occurring molecules. We developed a new visual analysis tool, X3DBio2, for 3D biomolecular structure comparison and analysis. The tool is designed for elucidation of structural effects of mutations in proteins and nucleic acids and for assessment of time dependent trajectories from molecular dynamics simulations. X3DBio2 is a freely downloadable open source software and provides tightly integrated features to perform many standard analysis and visual exploration tasks. We expect this tool can be applied to solve a variety of biological problems and illustrate the use of the tool on the example study of the differences and similarities between two proteins of the glycosyltransferase family 2 that synthesize polysaccharides oligomers. The size and conformational distances and retained core structural similarity of proteins SpsA to K4CP represent significant epochs in the evolution of inverting glycosyltransferases.

  13. Towards theoretical analysis of long-range proton transfer kinetics in biomolecular pumps

    PubMed Central

    König, P. H.; Ghosh, N.; Hoffmann, M.; Elstner, M.; Tajkhorshid, E.; Frauenheim, Th.; Cui, Q.

    2008-01-01

    Motivated by the long-term goal of theoretically analyzing long-range proton transfer (PT) kinetics in biomolecular pumps, a number of technical developments were made in the framework of QM/MM simulations. A set of collective reaction co-ordinates is proposed for characterizing the progress of long-range proton transfers; unlike previous suggestions, the new coordinates can describe PT along highly non-linear three-dimensional pathways. Calculations using a realistic model of carbonic anhydrase demonstrated that adiabatic mapping using these collective coordinates gives reliable energetics and critical geometrical parameters as compared to minimum energy path calculations, which suggests that the new coordinates can be effectively used as reaction coordinate in potential of mean force calculations for long-range PT in complex systems. In addition, the generalized solvent boundary potential was implemented in the QM/MM framework for rectangular geometries, which is useful for studying reactions in membrane systems. The resulting protocol was found to produce water structure in the interior of aquaporin consistent with previous studies including much larger number of explicit solvent and lipid molecules. The effect of electrostatics for PT through membrane protein was also illustrated with a simple model channel embedded in different dielectric continuum environments. The encouraging results observed so far suggest that robust theoretical analysis of long-range PT kinetics in biomolecular pumps can soon be realized in a QM/MM framework. PMID:16405327

  14. Group transfer theory of single molecule imaging experiments in the F-ATPase biomolecular motor

    NASA Astrophysics Data System (ADS)

    Volkan-Kacso, Sandor; Marcus, Rudolph

    I describe a chemo-mechanical theory to treat single molecule imaging and ``stalling'' experiments on the F-ATPase enzyme. This enzyme is an effective stepping biomolecular rotary motor with a rotor shaft and a stator ring. Using group transfer theoretical approach the proposed structure-based theory couples the binding transition of nucleotides in the stator subunits and the physics of torsional elasticity in the rotor. The twisting of the elastic rotor domain acts as a perturbation upon the driving potential, the Gibbs free energy. In the theory, without the use of adjustastable parameters, we predict the rate and equilibrium constant dependence of steps such as ATP binding and phosphate release as a function of manipulated rotor angle. Then we compare these predictions to available data from stalling experiments. Besides treating experiments, the theory can provide guides for atomistic simulations, which could calculate the reorganization parameter and the torsional spring constant. The framework is generic and I discuss its application to other single molecule experiments, such as controlled rotation and other biomolecular motors, including motor-DNA complexes and linear motors.[PNAS, Early Edition, Oct. 19, 2015, doi: 10.1073/pnas.1518489112] The authors would like to acknowledge support from the Office of the Naval Research, the Army Research Office, and the James W. Glanville Foundation.

  15. Group transfer theory of single molecule imaging experiments in the F-ATPase biomolecular motor

    NASA Astrophysics Data System (ADS)

    Volkan-Kacso, Sandor; Marcus, Rudolph

    I describe a chemo-mechanical theory to treat single molecule imaging and ``stalling'' experiments on the F-ATPase enzyme. This enzyme is an effective stepping biomolecular rotary motor with a rotor shaft and a stator ring. Using group transfer theoretical approach the proposed structure-based theory couples the binding transition of nucleotides in the stator subunits and the physics of torsional elasticity in the rotor. The twisting of the elastic rotor domain acts as a perturbation upon the driving potential, the Gibbs free energy. In the theory, without the use of adjustastable parameters, we predict the rate and equilibrium constant dependence of steps such as ATP binding and phosphate release as a function of manipulated rotor angle. Then we compare these predictions to available data from stalling experiments. Besides treating experiments, the theory can provide guides for atomistic simulations, which could calculate the reorganization parameter and the torsional spring constant. The framework is generic and I discuss its application to other single molecule experiments, such as controlled rotation and other biomolecular motors, including motor-DNA complexes and linear motors.[PNAS, Early Edition, Oct. 19, 2015, doi: 10.1073/pnas.1518489112

  16. The interplay of intrinsic and extrinsic bounded noises in biomolecular networks.

    PubMed

    Caravagna, Giulio; Mauri, Giancarlo; d'Onofrio, Alberto

    2013-01-01

    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. PMID:23437034

  17. Properties of the CO and H2O MOLsphere of the red supergiant Betelgeuse from VLTI/AMBER observations

    NASA Astrophysics Data System (ADS)

    Montargès, M.; Kervella, P.; Perrin, G.; Ohnaka, K.; Chiavassa, A.; Ridgway, S. T.; Lacour, S.

    2014-12-01

    Context. Betelgeuse is the closest red supergiant (RSG); therefore, it is well suited for studying the complex processes in its atmosphere that lead to the chemical enrichment of the interstellar medium. Aims: We intend to investigate the shape and composition of the close molecular layer (also known as the MOLsphere) that surrounds the star. This analysis is part of a wider program that aims at understanding the dynamics of the circumstellar envelope of Betelgeuse. Methods: On January and February 2011, Betelgeuse was observed using the Astronomical Multi-BEam combineR (AMBER) instrument of the Very Large Telescope Interferometer (VLTI) in the H and K bands. Using the medium spectral resolution of the instrument (R ~ 1500), we were able to investigate the carbon monoxide band heads and the water-vapor bands. We used two different approaches to analyse our data: a model fit in both the continuum and absorption lines and then a fit with a radiative hydrodynamics (RHD) simulation. Results: Using the continuum data, we derive a uniform disk diameter of 41.01 ± 0.41 mas, a power law type limb-darkened disk diameter of 42.28 ± 0.43 mas and a limb-darkening exponent of 0.155 ± 0.009. Within the absorption lines, using a single layer model, we obtain parameters of the MOLsphere. Using a RHD simulation, we unveil the convection pattern in the visibilities. Conclusions: We derived a new value of the angular diameter of Betelgeuse in the K band continuum. Our observations in the absorption lines are well reproduced by a molecular layer at 1.2 stellar radii containing both CO and H2O. The visibilities at higher spatial frequencies are matching a convection pattern in a RHD simulation. Based on AMBER observations made with ESO Telescopes at the Paranal Observatory under programmes ID 086.D-0351 and 286.D-5036(A).Table 1 is available in electronic form at http://www.aanda.org

  18. Further along the Road Less Traveled: AMBER ff15ipq, an Original Protein Force Field Built on a Self-Consistent Physical Model.

    PubMed

    Debiec, Karl T; Cerutti, David S; Baker, Lewis R; Gronenborn, Angela M; Case, David A; Chong, Lillian T

    2016-08-01

    We present the AMBER ff15ipq force field for proteins, the second-generation force field developed using the Implicitly Polarized Q (IPolQ) scheme for deriving implicitly polarized atomic charges in the presence of explicit solvent. The ff15ipq force field is a complete rederivation including more than 300 unique atomic charges, 900 unique torsion terms, 60 new angle parameters, and new atomic radii for polar hydrogens. The atomic charges were derived in the context of the SPC/Eb water model, which yields more-accurate rotational diffusion of proteins and enables direct calculation of nuclear magnetic resonance (NMR) relaxation parameters from molecular dynamics simulations. The atomic radii improve the accuracy of modeling salt bridge interactions relative to contemporary fixed-charge force fields, rectifying a limitation of ff14ipq that resulted from its use of pair-specific Lennard-Jones radii. In addition, ff15ipq reproduces penta-alanine J-coupling constants exceptionally well, gives reasonable agreement with NMR relaxation rates, and maintains the expected conformational propensities of structured proteins/peptides, as well as disordered peptides-all on the microsecond (μs) time scale, which is a critical regime for drug design applications. These encouraging results demonstrate the power and robustness of our automated methods for deriving new force fields. All parameters described here and the mdgx program used to fit them are included in the AmberTools16 distribution. PMID:27399642

  19. Further along the Road Less Traveled: AMBER ff15ipq, an Original Protein Force Field Built on a Self-Consistent Physical Model

    PubMed Central

    2016-01-01

    We present the AMBER ff15ipq force field for proteins, the second-generation force field developed using the Implicitly Polarized Q (IPolQ) scheme for deriving implicitly polarized atomic charges in the presence of explicit solvent. The ff15ipq force field is a complete rederivation including more than 300 unique atomic charges, 900 unique torsion terms, 60 new angle parameters, and new atomic radii for polar hydrogens. The atomic charges were derived in the context of the SPC/Eb water model, which yields more-accurate rotational diffusion of proteins and enables direct calculation of nuclear magnetic resonance (NMR) relaxation parameters from molecular dynamics simulations. The atomic radii improve the accuracy of modeling salt bridge interactions relative to contemporary fixed-charge force fields, rectifying a limitation of ff14ipq that resulted from its use of pair-specific Lennard-Jones radii. In addition, ff15ipq reproduces penta-alanine J-coupling constants exceptionally well, gives reasonable agreement with NMR relaxation rates, and maintains the expected conformational propensities of structured proteins/peptides, as well as disordered peptides—all on the microsecond (μs) time scale, which is a critical regime for drug design applications. These encouraging results demonstrate the power and robustness of our automated methods for deriving new force fields. All parameters described here and the mdgx program used to fit them are included in the AmberTools16 distribution. PMID:27399642

  20. Evolution of codes, crosstalk, and sequence niches in biomolecular signaling

    NASA Astrophysics Data System (ADS)

    Myers, Christopher

    2007-03-01

    Signaling and regulation in cellular networks is mediated through biomolecular interactions, which can be somewhat promiscuous, involving the molecular recognition of broad sets of binding targets. This leads to some basic questions concerning crosstalk among similar sets of biomolecules: does it occur, to what extent can it be avoided, how can phenotypic errors due to crosstalk be minimized, and when might crosstalk be advantageous? Beyond biology, questions of this sort have connections to phase transitions in constraint satisfaction problems, and to the theory of message coding in noisy channels. Expanding upon my previous work exploring the nature of the satisfiability (SAT-UNSAT) transition in a simple model of protein-protein interactions, this talk will investigate the role of sequence evolution in shaping high-dimensional sequence niches and biomolecular codes.

  1. Do biomolecular ion-motive ATPase work as adiabatic pumps

    NASA Astrophysics Data System (ADS)

    Astumian, Raymond Dean

    2001-03-01

    Biomolecular ion pumps use chemical energy to pump ions from low to high chemical potential across a biological membrane. Experiments show that the chemical energy can be substituted by an external oscillating or stochastically fluctuating electric field. This result can be interpreted analogously to a mechanism for an adiabatic electron pump originally suggested by Thouless (PRB 27: 6083 (1983)) in which two system parameters are modulated out of phase with one another. In our model, internal relaxations of the protein (at least two with different time scales) provide a mechanism for transforming a single ac or stochastically fluctuating external signal into a two phase shifted outputs. For a sinusoidally oscillating electric field, the frequency response for the Sodium-Potassium ATPase for both sodium and rubidium (an analog of potassium) can be fit using a very simple expression with only one fit parameter. These results show how biomolecular pumps can be modelled at the mesoscopic level of detail.

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

    PubMed

    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. PMID:26137457

  3. Direct Observation of Kinetic Pathways of Biomolecular Recognition.

    PubMed

    Choudhury, Susobhan; Batabyal, Subrata; Mondal, Prasanna Kumar; Singh, Priya; Lemmens, Peter; Pal, Samir Kumar

    2015-11-01

    The pathways of molecular recognition, which is a central event in all biological processes, belong to the most important subjects of contemporary research in biomolecular science. By using fluorescence spectroscopy in a microfluidics channel, it can be determined that molecular recognition of α-chymotrypsin in hydrous surroundings at two different pH values (3.6 and 6.3) follows two distinctly different pathways. Whereas one corroborates an induced-fit model (pH 3.6), the other one (pH 6.3) is consistent with the selected-fit model of biomolecular recognition. The role of massive structural perturbations of differential recognition pathways could be ruled out by earlier XRD studies, rather was consistent with the femtosecond-resolved observation of dynamic flexibility of the protein at different pH values. At low concentrations of ligands, the selected-fit model dominates, whereas increasing the ligand concentration leads to the induced-fit model. From molecular modelling and experimental results, the timescale associated with the conformational flexibility of the protein plays a key role in the selection of a pathway in biomolecular recognition. PMID:26367136

  4. Optically Resonant Nanophotonic Devices for Label-Free Biomolecular Detection

    NASA Astrophysics Data System (ADS)

    Goddard, Julie; Mandal, Sudeep; Erickson, David

    Optical devices, such as surface plasmon resonance chips and waveguide-based Mach-Zehnder interferometers, have long been successfully used as label-free biomolecular sensors. Recently, however, there has been increased interest in developing new approaches to biomolecular detection that can improve on the limit of detection, specificity, and multiplexibility of these early devices and address emerging challenges in pathogen detection, disease diagnosis, and drug discovery. As we describe in this chapter, planar optically resonant nanophotonic devices (such as ring resonators, whispering gallery modes, and photonic crystal cavities) are one method that shows promise in significantly advancing the technology. Here we first provide a short review of these devices focusing on a handful of approaches illustrative of the state of the art. We then frame the major challenge to improving the technology as being the ability to provide simultaneously spatial localization of the electromagnetic energy and biomolecular binding events. We then introduce our “Nanoscale Optofluidic Sensor Arrays” which represents our approach to addressing this challenge. It is demonstrated how these devices serve to enable multiplexed detection while localizing the electromagnetic energy to a volume as small as a cubic wavelength. Challenges involved in the targeted immobilization of biomolecules over such a small area are discussed and our solutions presented. In general, we have tried to write this chapter with the novice in mind, providing details on the fabrication and immobilization methods that we have used and how one might adapt our approach to their designs.

  5. Biomolecular recognition and detection using gold-based nanoprobes

    NASA Astrophysics Data System (ADS)

    Crew, Elizabeth

    The ability to control the biomolecular interactions is important for developing bioanalytical probes used in biomolecule and biomarker detections. This work aims at a fundamental understanding of the interactions and reactivities involving DNA, miRNA, and amino acids using gold-based nanoparticles as nanoprobes, which has implications for developing new strategies for the early detection of diseases, such as cancer, and controlled delivery of drugs. Surface modifications of the nanoprobes with DNA, miRNA, and amino acids and the nanoprobe directed biomolecular reactivities, such as complementary-strand binding, enzymatic cutting and amino acid interactions, have been investigated. Among various analytical techniques employed for the analysis of the biomolecule-nanoprobe interactions, surface enhanced Raman scattering spectroscopy (SERS) has been demonstrated to provide a powerful tool for real time monitoring of the DNA assembly and enzymatic cutting processes in solutions. This demonstration harnesses the "hot-spot" characteristic tuned by the interparticle biomolecular-regulated interactions and distances. The assembly of gold nanoparticles has also been exploited as sensing thin films on chemiresistor arrays for the detection of volatile organic compounds, including biomarker molecules associated with diabetes. Important findings of the nanoprobes in delivering miRNA to cells, detecting DNA hybridization kinetics, discerning chiral recognition with enantiomeric cysteines, and sensing biomarker molecules with the nanostructured thin films will be discussed, along with their implications to enhancing sensitivity, selectivity and limits of detection.

  6. Retroactivity in the Context of Modularly Structured Biomolecular Systems

    PubMed Central

    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. PMID:26137457

  7. Terrestrial soft-bodied protists and other microorganisms in triassic amber.

    PubMed

    Poinar, G O; Waggoner, B M; Bauer, U C

    1993-01-01

    Protozoa, cyanobacteria, sheathed algae, sheathed fungi, germinating pollen or spores, and fungal spores have been found in amber 220 to 230 million years old. Many of these microorganisms can be assigned to present-day groups. This discovery of terrestrial, soft-bodied protists that can be referred to modern groups indicates that morphological evolution is very gradual in many protists and that both structural and probably functional stasis extend back at least to the Upper Triassic period. PMID:17790989

  8. Amber light-emitting diode comprising a group III-nitride nanowire active region

    DOEpatents

    Wang, George T.; Li, Qiming; Wierer, Jr., Jonathan J.; Koleske, Daniel

    2014-07-22

    A temperature stable (color and efficiency) III-nitride based amber (585 nm) light-emitting diode is based on a novel hybrid nanowire-planar structure. The arrays of GaN nanowires enable radial InGaN/GaN quantum well LED structures with high indium content and high material quality. The high efficiency and temperature stable direct yellow and red phosphor-free emitters enable high efficiency white LEDs based on the RGYB color-mixing approach.

  9. Cyclic terpenoids of contemporary resinous plant detritus and of fossil woods, ambers and coals

    USGS Publications Warehouse

    Simoneit, B.R.T.; Grimalt, J.O.; Wang, T.-G.; Cox, R.E.; Hatcher, P.G.; Nissenbaum, A.

    1986-01-01

    Cyclic terpenoids present in the solvent extractable material of fossil woods, ambers and brown coals have been analyzed. The sample series chosen consisted of wood remains preserved in Holocene to Jurassic sediments and a set of of ambers from the Philippines (copalite), Israel, Canada and Dominican Republic. The brown coals selected were from the Fortuna Garsdorf Mine and Miocene formations on Fiji. The fossil wood extracts contained dominant diterpenoid or sesquiterpenoid skeletons, and aromatized species were present at high concentrations, with a major amount of two-ring aromatic compounds. Tricyclic diterpenoids were the predominant compounds in the ambers. Aromatized derivatives were the major components, consisting of one or two aromatic ring species with the abietane and occasionally pimarane skeletons. The saturated structures were comprised primarily of the abietane and pimarane skeletons having from three to five carbon (C1, C2, etc.) substituents. Kaurane and phyllocladane isomers were present in only minor amounts. Bicyclic sesquiterpenoids as saturated and partial or fully aromatized forms were also common in these samples, but only traces of sesterterpenoids and triterpenoid derivatives were found. The brown coal extracts were composed of major amounts of one- and two-ring aromatized terpenoids, with a greater proportion of triterpenoid derivatives than in the case of the woods and ambers. This was especially noticeable for the German coal, where the triterpenoids were predominant. Open C-ring aromatized structures were also present in this coal. Steroid compounds were not detectable, but some hopanes were found as minor components in the German brown coal. An overview of the skeletal structure classes identified in each sample, as well as the general mass spectrometric characteristics of the unknown compounds are included in the present paper. It can be concluded from these structural distributions that aromatization is the main process for the

  10. A new species of Proceroplatus Edwards (Diptera: Keroplatidae) in Miocene amber from the Dominican Republic.

    PubMed

    Penney, David; Evenhuis, Neal L; Green, David I

    2013-01-01

    Keroplatid fungus gnats (Diptera: Keroplatidae) were hitherto known from the Caribbean island of Hispaniola from a single named species in Miocene amber from the Dominican Republic. Here we describe the new fossil species Proceroplatus preziosii Evenhuis & Penney based on a mature male specimen, which differs markedly from both fossil and extant taxa in the structure of its gonostyli and U-shaped wing pattern. We also document the first record of extant Keroplatidae, Proceroplatus pictipennis (Williston), from Hispaniola. PMID:26473245

  11. A new genus of fossil Mymaridae (Hymenoptera) from Cretaceous amber and key to Cretaceous mymarid genera.

    PubMed

    Poinar, George; Huber, John T

    2011-01-01

    Myanmymar aresconoidesgen n., sp. n. is described from one female in Burmese amber, dated as about 100 my. It is similar to Arescon on wing features but is unique among Mymaridae in having distinctly segmented palpi. It is the fifth mymarid genus definitely referable to the Cretaceous period. A key to Cretaceous mymarid genera is presented and the features of Myanmymar are compared with the other Cretaceous and extant mymarid genera. PMID:22259293

  12. The oldest micropepline beetle from Cretaceous Burmese amber and its phylogenetic implications (Coleoptera: Staphylinidae)

    NASA Astrophysics Data System (ADS)

    Cai, Chen-Yang; Huang, Di-Ying

    2014-10-01

    The staphylinid subfamily Micropeplinae includes small strongly sclerotized beetles with truncate elytra leaving the most part of abdomen exposed. Fossil micropeplines are rare and confined to Cenozoic representatives of extant genera. Here, we describe the oldest micropepline, Protopeplus cretaceus gen. and sp. n., from the Upper Cretaceous Burmese amber. Fluorescence microscope and confocal laser scanning microscopy (CLSM) were both used to reveal diagnostic features of Micropeplinae and some primitive traits that place Protopeplus very basally within Micropeplinae.

  13. A new genus of fossil Mymaridae (Hymenoptera) from Cretaceous amber and key to Cretaceous mymarid genera

    PubMed Central

    Poinar Jr., George; Huber, John T.

    2011-01-01

    Abstract Myanmymar aresconoides gen n., sp. n. is described from one female in Burmese amber, dated as about 100 my. It is similar to Arescon on wing features but is unique among Mymaridae in having distinctly segmented palpi. It is the fifth mymarid genus definitely referable to the Cretaceous period. A key to Cretaceous mymarid genera is presented and the features of Myanmymar are compared with the other Cretaceous and extant mymarid genera. PMID:22259293

  14. Differential expression of five tRNA(UAGTrp) amber suppressors in Caenorhabditis elegans.

    PubMed Central

    Kondo, K; Hodgkin, J; Waterston, R H

    1988-01-01

    Caenorhabditis elegans has 12 tRNA(UGGTrp) genes as defined by Southern analysis. In order to evaluate the function of the individual members of this multigene family, we sought to recover amber (UAG)-suppressing mutations from reversion experiments with animals carrying amber mutations in a nervous system-affecting gene (unc-13) or a sex-determining gene (tra-3). Revertants were analyzed by Southern blot, exploiting the fact that the CCA to CTA change at the anticodon creates a new XbaI site. Five different members of the tRNATrp gene family were identified as suppressors: sup-7 X, sup-5 III, sup-24 IV, sup-28 X, and sup-29 IV. All five suppressor genes were sequenced and found to encode identical tRNA(UAGTrp) molecules with a single base change (CCA to CTA) at the anticodon compared with their wild-type counterparts. The flanking sequences had only limited homology. The relative expression of these five genes was determined by measuring the efficiencies of suppressers against amber mutations in genes affecting the nervous system, hypodermis, muscle, and sex determination. The results of these cross-suppression tests showed that the five members of the tRNA(Trp) gene family were differentially regulated in a tissue- or development stage-specific manner. Images PMID:3221861

  15. DNA Changes in Tissues Entrapped in Plant Resins (the Precursors of Amber)

    NASA Astrophysics Data System (ADS)

    Rogers, S. O.; Langenegger, K.; Holdenrieder, O.

    There have been many reports characterizing DNA from amber, which is a fossil version of plant resin. Here we report an investigation of the effects of plant resin (from Pseudotsuga menziesii) and drying conditions on the preservation of DNA in biological tissues. We examined the degree of degradation of the DNA by agarose gel electrophoresis of extracted DNA, by polymerase chain reaction, and by DNA sequencing. The plant resin alone appeared to cause little or no damage to DNA. Tissue immersed in plant resin that dried rapidly (exposed to sunlight) contained DNA with little apparent damage. Tissue immersed in the resin that was dried slowly (in shade without sunlight) contained DNA with some degradation (3.5% nucleotide changes). The tissue that was immersed in the resin that was constantly hydrated (by immersion in water) yielded DNA that was severely damaged (50-62% nucleotide changes). Transversions outnumbered transitions in these samples by a ratio of 1.4 : 1. A piece of Baltic amber immersed in water for 5days appeared to be impervious to the water. Thus amber inclusions that initially dried rapidly have the potential to yield undamaged DNA. Those that dried slowly may contain damaged DNA and may be unsuitable for phylogenetic and other studies.

  16. Manufacturable conducting rubber ambers and stretchable conductors from copper nanowire aerogel monoliths.

    PubMed

    Tang, Yue; Gong, Shu; Chen, Yi; Yap, Lim Wei; Cheng, Wenlong

    2014-06-24

    We report on a low-cost, simple yet efficient strategy to fabricate ultralightweight aerogel monoliths and conducting rubber ambers from copper nanowires (CuNWs). A trace amount of poly(vinyl alcohol) (PVA) substantially improved the mechanical robustness and elasticity of the CuNW aerogel while maintaining a high electrical conductivity. The resistivity was highly responsive to strains manifesting two distinct domains, and both followed a power law function consistent with pressure-controlled percolation theory. However, the values of the exponents were much less than the predicted value for 3D systems, which may be due to highly porous structures. Remarkably, the CuNW-PVA aerogels could be further embedded into PDMS resin, forming conducting rubber ambers. The ambers could be further manufactured simply by cutting into any arbitrary 1D, 2D, and 3D shapes, which were all intrinsically conductive without the need of external prewiring, a condition required in the previous aerogel-based conductors. The outstanding electrical conductivity in conjunction with high mechanical compliance enabled prototypes of the elastic piezoresistivity switches and stretchable conductors. PMID:24873318

  17. The anamorphic genus Monotosporella (Ascomycota) from Eocene amber and from modern Agathis resin.

    PubMed

    Sadowski, Eva-Maria; Beimforde, Christina; Gube, Matthias; Rikkinen, Jouko; Singh, Hukam; Seyfullah, Leyla J; Heinrichs, Jochen; Nascimbene, Paul C; Reitner, Joachim; Schmidt, Alexander R

    2012-10-01

    The anamorphic fungal genus Monotosporella (Ascomycota, Sordariomycetes) has been reco-vered from a piece of Early Eocene Indian amber, as well as from the surface of extant resin flows in New Caledonia. The fossil fungus was obtained from the Tarkeshwar Lignite Mine of Gujarat State, western India, and was part of the biota of an early tropical angiosperm rainforest. The amber inclusion represents the second fossil record of Sordariomycetes, as well as the first fossil of its particular order (either Savoryellales or Chaetosphaeriales). The fossil fungus is distinguished from extant representatives by possessing both short conidiophores and small two-septate pyriform conidia, and is described as Monotosporella doerfeltii sp. nov. Inside the amber, the anamorph is attached to its substrate, which is likely the degraded thallus of a cladoniform lichen. The extant New Caledonian species is assigned to Monotosporella setosa. It was found growing on semi-solidified resin flows of Agathis ovata (Araucariaceae), and is the first record of Monotosporella from modern resin substrates. PMID:23063189

  18. Computed tomography recovers data from historical amber: an example from huntsman spiders

    NASA Astrophysics Data System (ADS)

    Dunlop, Jason A.; Penney, David; Dalüge, Natalie; Jäger, Peter; McNeil, Andrew; Bradley, Robert S.; Withers, Philip J.; Preziosi, Richard F.

    2011-06-01

    Computed tomography (CT) methods were applied to a problematic fossil spider (Arachnida: Araneae) from the historical Berendt collection of Eocene (ca. 44-49 Ma) Baltic amber. The original specimens of Ocypete crassipes Koch and Berendt 1854 are in dark, oxidised amber and the published descriptions lack detail. Despite this, they were subsequently assigned to the living Pantropical genus Heteropoda Latreille, 1804 and are ostensibly the oldest records of huntsman spiders (Sparassidae) in general. Given their normally large size, and presumptive ability to free themselves more easily from resin, it would be surprising to find a sparassid in amber and traditional (optical) methods of study would likely have left O. crassipes as an equivocal record—probably a nomen dubium. However, phase contrast enhanced X-ray CT revealed exquisite morphological detail and thus `saved' this historical name by revealing characters which confirm that it's a bona fide member both of Sparassidae and the subfamily Eusparassinae. We demonstrate here that CT studies facilitate taxonomic equivalence even between recent spiders and unpromising fossils described in older monographs. In our case, fine structural details such as eye arrangement, cheliceral dentition, and leg characters like a trilobate membrane, spination and claws, allow a precise referral of this fossil to an extant genus as Eusparassus crassipes (Koch and Berendt 1854) comb. nov.

  19. Gas bubbles in fossil amber as possible indicators of the major gas composition of ancient air

    USGS Publications Warehouse

    Berner, R.A.; Landis, G.P.

    1988-01-01

    Gases trapped in Miocene to Upper Cretaceous amber were released by gently crushing the amber under vacuum and were analyzed by quadrupole mass spectrometry. After discounting the possibility that the major gases N2, O2, and CO2 underwent appreciable diffusion and diagenetic exchange with their surroundings or reaction with the amber, it has been concluded that in primary bubbles (gas released during initial breakage) these gases represent mainly original ancient air modified by the aerobic respiration of microorganisms. Values of N2/(CO2+O2) for each time period give consistent results despite varying O2/CO2 ratios that presumably were due to varying degrees of respiration. This allows calculation of original oxygen concentrations, which, on the basis of these preliminary results, appear to have changed from greater than 30 percent O2 during one part ofthe Late Cretaceous (between 75 and 95 million years ago) to 21 percent during the Eocene-Oligocene and for present-day samples, with possibly lower values during the Oligocene-Early Miocene. Variable O2 levels over time in general confirm theoretical isotope-mass balance calculations and suggest that the atmosphere has evolved over Phanerozoic time.

  20. Gold nanoshells with gain-assisted silica core for ultra-sensitive bio-molecular sensors

    NASA Astrophysics Data System (ADS)

    Tao, Yifei; Guo, Zhongyi; Zhang, Anjun; Zhang, Jingran; Wang, Benyang; Qu, Shiliang

    2015-08-01

    A novel bio-molecular nanostructured sensor composed of Au spherical nanoshell and gain-assisted silica-core has been proposed and investigated theoretically, which shows a superior performance compared to the existing structured sensor. Using quasi-static approximation calculation, it is found that the scattering efficiency and the quality factor of SPR can be enhanced greatly by introducing proper amount of gain. The simulated results demonstrate that our designed Au spherical nanoshell and gain-assisted silica-core can obtain as high as 166.7 nm/RIU for the sensitivity of refractive index, and the sensors' figure of merit is enhanced 2000 times nearly compared to that of g=0, which indicates that the designed spherical core-shell sensors have the powerful ability to detect a subtle change in the concentration of its background medium.

  1. Mathematical approaches to biomolecular structure and dynamics

    SciTech Connect

    Mesirov, J.P.; Sumners, D.W.; Schulten, K.

    1996-12-31

    The revolutionary progress in molecular biology within the last 30 years opens the way to full understanding of the molecular structures and mechanisms of living organisms. The papers in this volume cover the spectrum from experiment to computation to simulation to theory. This is one of two volumes based on the proceedings of the 1994 IMA Summer Program on Molecular Biology and comprises Weeks 3 and 4 of the four-week program. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  2. Enhanced semiempirical QM methods for biomolecular interactions

    PubMed Central

    Yilmazer, Nusret Duygu; Korth, Martin

    2015-01-01

    Recent successes and failures of the application of ‘enhanced’ semiempirical QM (SQM) methods are reviewed in the light of the benefits and backdraws of adding dispersion (D) and hydrogen-bond (H) correction terms. We find that the accuracy of SQM-DH methods for non-covalent interactions is very often reported to be comparable to dispersion-corrected density functional theory (DFT-D), while computation times are about three orders of magnitude lower. SQM-DH methods thus open up a possibility to simulate realistically large model systems for problems both in life and materials science with comparably high accuracy. PMID:25848495

  3. ff14ipq: A Self-Consistent Force Field for Condensed-Phase Simulations of Proteins.

    PubMed

    Cerutti, David S; Swope, William C; Rice, Julia E; Case, David A

    2014-10-14

    We present the ff14ipq force field, implementing the previously published IPolQ charge set for simulations of complete proteins. Minor modifications to the charge derivation scheme and van der Waals interactions between polar atoms are introduced. Torsion parameters are developed through a generational learning approach, based on gas-phase MP2/cc-pVTZ single-point energies computed of structures optimized by the force field itself rather than the quantum benchmark. In this manner, we sacrifice information about the true quantum minima in order to ensure that the force field maintains optimal agreement with the MP2/cc-pVTZ benchmark for the ensembles it will actually produce in simulations. A means of making the gas-phase torsion parameters compatible with solution-phase IPolQ charges is presented. The ff14ipq model is an alternative to ff99SB and other Amber force fields for protein simulations in programs that accommodate pair-specific Lennard-Jones combining rules. The force field gives strong performance on α-helical and β-sheet oligopeptides as well as globular proteins over microsecond time scale simulations, although it has not yet been tested in conjunction with lipid and nucleic acid models. We show how our choices in parameter development influence the resulting force field and how other choices that may have appeared reasonable would actually have led to poorer results. The tools we developed may also aid in the development of future fixed-charge and even polarizable biomolecular force fields. PMID:25328495

  4. ff14ipq: A Self-Consistent Force Field for Condensed-Phase Simulations of Proteins

    PubMed Central

    2015-01-01

    We present the ff14ipq force field, implementing the previously published IPolQ charge set for simulations of complete proteins. Minor modifications to the charge derivation scheme and van der Waals interactions between polar atoms are introduced. Torsion parameters are developed through a generational learning approach, based on gas-phase MP2/cc-pVTZ single-point energies computed of structures optimized by the force field itself rather than the quantum benchmark. In this manner, we sacrifice information about the true quantum minima in order to ensure that the force field maintains optimal agreement with the MP2/cc-pVTZ benchmark for the ensembles it will actually produce in simulations. A means of making the gas-phase torsion parameters compatible with solution-phase IPolQ charges is presented. The ff14ipq model is an alternative to ff99SB and other Amber force fields for protein simulations in programs that accommodate pair-specific Lennard–Jones combining rules. The force field gives strong performance on α-helical and β-sheet oligopeptides as well as globular proteins over microsecond time scale simulations, although it has not yet been tested in conjunction with lipid and nucleic acid models. We show how our choices in parameter development influence the resulting force field and how other choices that may have appeared reasonable would actually have led to poorer results. The tools we developed may also aid in the development of future fixed-charge and even polarizable biomolecular force fields. PMID:25328495

  5. Optimizing Protein-Protein van der Waals Interactions for the AMBER ff9x/ff12 Force Field.

    PubMed

    Chapman, Dail E; Steck, Jonathan K; Nerenberg, Paul S

    2014-01-14

    The quality of molecular dynamics (MD) simulations relies heavily on the accuracy of the underlying force field. In recent years, considerable effort has been put into developing more accurate dihedral angle potentials for MD force fields, but relatively little work has focused on the nonbonded parameters, many of which are two decades old. In this work, we assess the accuracy of protein-protein van der Waals interactions in the AMBER ff9x/ff12 force field. Across a test set of 44 neat organic liquids containing the moieties present in proteins, we find root-mean-square (RMS) errors of 1.26 kcal/mol in enthalpy of vaporization and 0.36 g/cm(3) in liquid densities. We then optimize the van der Waals radii and well depths for all of the relevant atom types using these observables, which lowers the RMS errors in enthalpy of vaporization and liquid density of our validation set to 0.59 kcal/mol (53% reduction) and 0.019 g/cm(3) (46% reduction), respectively. Limitations in our parameter optimization were evident for certain atom types, however, and we discuss the implications of these observations for future force field development. PMID:26579910

  6. High spectral resolution imaging of the dynamical atmosphere of the red supergiant Antares in the CO first overtone lines with VLTI/AMBER

    NASA Astrophysics Data System (ADS)

    Ohnaka, K.; Hofmann, K.-H.; Schertl, D.; Weigelt, G.; Baffa, C.; Chelli, A.; Petrov, R.; Robbe-Dubois, S.

    2013-07-01

    luminosity of log L⋆/L⊙ = 4.88 ± 0.23. Comparison with theoretical evolutionary tracks suggests a mass of 15 ± 5 M⊙ with an age of 11-15 Myr, which is consistent with the recently estimated age for the Upper Scorpius OB association. Conclusions: The properties of the outer atmosphere of Antares are similar to those of another well-studied red supergiant, Betelgeuse. The density of the extended outer atmosphere of Antares and Betelgeuse is higher than predicted by the current 3D convection simulations by at least six orders of magnitude, implying that convection alone cannot explain the formation of the extended outer atmosphere. Based on AMBER observations made with the Very Large Telescope Interferometer of the European Southern Observatory. Program ID: 083.D-0333(A/B) (AMBER guaranteed time observation), 085.D-0085(A/B).Appendices are available in electronic form at http://www.aanda.orgMovies of data cube are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/555/A24

  7. Molecular Dynamics Simulations of Simple Liquids

    ERIC Educational Resources Information Center

    Speer, Owner F.; Wengerter, Brian C.; Taylor, Ramona S.

    2004-01-01

    An experiment, in which students were given the opportunity to perform molecular dynamics simulations on a series of molecular liquids using the Amber suite of programs, is presented. They were introduced to both physical theories underlying classical mechanics simulations and to the atom-atom pair distribution function.

  8. Quantitative analysis of numerical solvers for oscillatory biomolecular system models

    PubMed Central

    Quo, Chang F; Wang, May D

    2008-01-01

    Background This article provides guidelines for selecting optimal numerical solvers for biomolecular system models. Because various parameters of the same system could have drastically different ranges from 10-15 to 1010, the ODEs can be stiff and ill-conditioned, resulting in non-unique, non-existing, or non-reproducible modeling solutions. Previous studies have not examined in depth how to best select numerical solvers for biomolecular system models, which makes it difficult to experimentally validate the modeling results. To address this problem, we have chosen one of the well-known stiff initial value problems with limit cycle behavior as a test-bed system model. Solving this model, we have illustrated that different answers may result from different numerical solvers. We use MATLAB numerical solvers because they are optimized and widely used by the modeling community. We have also conducted a systematic study of numerical solver performances by using qualitative and quantitative measures such as convergence, accuracy, and computational cost (i.e. in terms of function evaluation, partial derivative, LU decomposition, and "take-off" points). The results show that the modeling solutions can be drastically different using different numerical solvers. Thus, it is important to intelligently select numerical solvers when solving biomolecular system models. Results The classic Belousov-Zhabotinskii (BZ) reaction is described by the Oregonator model and is used as a case study. We report two guidelines in selecting optimal numerical solver(s) for stiff, complex oscillatory systems: (i) for problems with unknown parameters, ode45 is the optimal choice regardless of the relative error tolerance; (ii) for known stiff problems, both ode113 and ode15s are good choices under strict relative tolerance conditions. Conclusions For any given biomolecular model, by building a library of numerical solvers with quantitative performance assessment metric, we show that it is possible

  9. Evaluating thermodynamic integration performance of the new amber molecular dynamics package and assess potential halogen bonds of enoyl-ACP reductase (FabI) benzimidazole inhibitors.

    PubMed

    Su, Pin-Chih; Johnson, Michael E

    2016-04-01

    Thermodynamic integration (TI) can provide accurate binding free energy insights in a lead optimization program, but its high computational expense has limited its usage. In the effort of developing an efficient and accurate TI protocol for FabI inhibitors lead optimization program, we carefully compared TI with different Amber molecular dynamics (MD) engines (sander and pmemd), MD simulation lengths, the number of intermediate states and transformation steps, and the Lennard-Jones and Coulomb Softcore potentials parameters in the one-step TI, using eleven benzimidazole inhibitors in complex with Francisella tularensis enoyl acyl reductase (FtFabI). To our knowledge, this is the first study to extensively test the new AMBER MD engine, pmemd, on TI and compare the parameters of the Softcore potentials in the one-step TI in a protein-ligand binding system. The best performing model, the one-step pmemd TI, using 6 intermediate states and 1 ns MD simulations, provides better agreement with experimental results (RMSD = 0.52 kcal/mol) than the best performing implicit solvent method, QM/MM-GBSA from our previous study (RMSD = 3.00 kcal/mol), while maintaining similar efficiency. Briefly, we show the optimized TI protocol to be highly accurate and affordable for the FtFabI system. This approach can be implemented in a larger scale benzimidazole scaffold lead optimization against FtFabI. Lastly, the TI results here also provide structure-activity relationship insights, and suggest the parahalogen in benzimidazole compounds might form a weak halogen bond with FabI, which is a well-known halogen bond favoring enzyme. PMID:26666582

  10. Water-soluble luminescent quantum dots and biomolecular conjugates thereof and related compositions and method of use

    DOEpatents

    Nie, Shuming; Chan, Warren C. W.; Emory, Steven R.

    2002-01-01

    The present invention provides a water-soluble luminescent quantum dot, a biomolecular conjugate thereof and a composition comprising such a quantum dot or conjugate. Additionally, the present invention provides a method of obtaining a luminescent quantum dot, a method of making a biomolecular conjugate thereof, and methods of using a biomolecular conjugate for ultrasensitive nonisotopic detection in vitro and in vivo.

  11. Water-soluble luminescent quantum dots and biomolecular conjugates thereof and related compositions and methods of use

    DOEpatents

    Nie, Shuming; Chan, Warren C. W.; Emory, Stephen

    2007-03-20

    The present invention provides a water-soluble luminescent quantum dot, a biomolecular conjugate thereof and a composition comprising such a quantum dot or conjugate. Additionally, the present invention provides a method of obtaining a luminescent quantum dot, a method of making a biomolecular conjugate thereof, and methods of using a biomolecular conjugate for ultrasensitive nonisotopic detection in vitro and in vivo.

  12. Fossilised microcenoses and microdebris in Cretaceous amber Alava (Spain) explored using several microscopy techniques

    NASA Astrophysics Data System (ADS)

    Ascaso, C.; Wierzchos, J.; Corral, J. C.; López, R.; Alonso, J.

    2003-04-01

    It is obvious that Mars return missions are not likely to provide us with fossil-bearing amber resins. Nonetheless, there is much to learn from the study of the biodiversity of fossilised microorganisms, their fossilization processes and detection strategies. In particular, if we are able to determine the endurance of biomolecules in this ancient material, this might contribute to existing knowledge on the persistence of dormant forms over millennia. Amber is a superb medium for the fossilization of organisms. Besides light microscopy techniques, this report describes the use of scanning electron microscopy both in backscattered electron (SEM-BSE) and low temperature (LTSEM) modes, and confocal laser scanning microscopy to examine microorganisms and microdebris (remains of pluricellular organisms). These novel techniques were applied to inclusions in amber (dated as Allaian: Early Cretaceous) from Álava (N Spain). Confocal microscopy provides a 3D image of microcenoses showing very well preserved biomolecules; fungal hyphae and protozoan cells emitting a strong autofluorescence signal. The huge potential of SEM-BSE was demonstrated by high resolution images, in which the relationship between fossilized (mineralized) protozoa and fungal hyphae could be observed. Moreover, this technique enabled the observation and description of further ultrastructural details of the cytoplasm of protozoa and fungal hyphae. Energy dispersive X-ray spectroscopy revealed that protozoan and fungal cells were transformed by mineralisation process into fossils composed of iron sulphide with highly preserved ultrastructural details. LTSEM performed on protozoan inclusions generated images showing many vacuoles. Finally, SEM in secondary electron detection mode was found to provide micromorphological information on mummified (not mineralized) bacteria-like microbiota trapped in gas bubbles

  13. Parameters for the AMBER force field for the molecular mechanics modeling of the cobalt corrinoids

    NASA Astrophysics Data System (ADS)

    Marques, H. M.; Ngoma, B.; Egan, T. J.; Brown, K. L.

    2001-04-01

    Additional parameters for the AMBER force field have been developed for the molecular mechanics modeling of the cobalt corrinoids. Parameter development was based on a statistical analysis of the reported structures of these compounds. The resulting force field reproduces bond lengths, bond angles, and torsional angles within 0.01 Å, 0.8°, and 4.0° of the mean crystallographic values, respectively. Parameters for the Co-C bond length and the Co-C-C bond angle for modeling the alkylcobalamins were developed by modeling six alkylcobalamins. The validity of the force field was tested by comparing the results obtained with known experimental features of the structures of the cobalt corrinoids as well as with the results from their modeling using a parameter set for the MM2 force field that has been previously developed and extensively tested. The AMBER force field reproduces the structures of the cobalt corrinoids as well as the MM2 force field, although it tends to underestimate the corrin fold angle, the angle between mean planes through the corrin atoms in the northern and southern half of the molecules, respectively. The force field was applied to a study of the structures of 5'-deoxy-5'-(3-isoadenosyl)cobalamin, 2',5'-dideoxy-5'-adenosylcobalamin and 2',3',5'-trideoxy-5'-adenosylcobalamin. This expansion of the standard AMBER force field provides a force field that can be used for modeling the structures of the B 12-dependent proteins, the structures of some of which are now beginning to emerge. This was verified in a preliminary modeling of the coenzyme B 12 binding site of methylmalonyl coenzyme A mutase.

  14. Perspective: Coarse-grained models for biomolecular systems

    NASA Astrophysics Data System (ADS)

    Noid, W. G.

    2013-09-01

    By focusing on essential features, while averaging over less important details, coarse-grained (CG) models provide significant computational and conceptual advantages with respect to more detailed models. Consequently, despite dramatic advances in computational methodologies and resources, CG models enjoy surging popularity and are becoming increasingly equal partners to atomically detailed models. This perspective surveys the rapidly developing landscape of CG models for biomolecular systems. In particular, this review seeks to provide a balanced, coherent, and unified presentation of several distinct approaches for developing CG models, including top-down, network-based, native-centric, knowledge-based, and bottom-up modeling strategies. The review summarizes their basic philosophies, theoretical foundations, typical applications, and recent developments. Additionally, the review identifies fundamental inter-relationships among the diverse approaches and discusses outstanding challenges in the field. When carefully applied and assessed, current CG models provide highly efficient means for investigating the biological consequences of basic physicochemical principles. Moreover, rigorous bottom-up approaches hold great promise for further improving the accuracy and scope of CG models for biomolecular systems.

  15. Biomolecular Events in Cancer Revealed by Attractor Metagenes

    PubMed Central

    Cheng, Wei-Yi; Yang, Tai-Hsien Ou; Anastassiou, Dimitris

    2013-01-01

    Mining gene expression profiles has proven valuable for identifying signatures serving as surrogates of cancer phenotypes. However, the similarities of such signatures across different cancer types have not been strong enough to conclude that they represent a universal biological mechanism shared among multiple cancer types. Here we present a computational method for generating signatures using an iterative process that converges to one of several precise attractors defining signatures representing biomolecular events, such as cell transdifferentiation or the presence of an amplicon. By analyzing rich gene expression datasets from different cancer types, we identified several such biomolecular events, some of which are universally present in all tested cancer types in nearly identical form. Although the method is unsupervised, we show that it often leads to attractors with strong phenotypic associations. We present several such multi-cancer attractors, focusing on three that are prominent and sharply defined in all cases: a mesenchymal transition attractor strongly associated with tumor stage, a mitotic chromosomal instability attractor strongly associated with tumor grade, and a lymphocyte-specific attractor. PMID:23468608

  16. A biomolecular isolation framework for eco-systems biology.

    PubMed

    Roume, Hugo; Muller, Emilie E L; Cordes, Thekla; Renaut, Jenny; Hiller, Karsten; Wilmes, Paul

    2013-01-01

    Mixed microbial communities are complex, dynamic and heterogeneous. It is therefore essential that biomolecular fractions obtained for high-throughput omic analyses are representative of single samples to facilitate meaningful data integration, analysis and modeling. We have developed a new methodological framework for the reproducible isolation of high-quality genomic DNA, large and small RNA, proteins, and polar and non-polar metabolites from single unique mixed microbial community samples. The methodology is based around reproducible cryogenic sample preservation and cell lysis. Metabolites are extracted first using organic solvents, followed by the sequential isolation of nucleic acids and proteins using chromatographic spin columns. The methodology was validated by comparison to traditional dedicated and simultaneous biomolecular isolation methods. To prove the broad applicability of the methodology, we applied it to microbial consortia of biotechnological, environmental and biomedical research interest. The developed methodological framework lays the foundation for standardized molecular eco-systematic studies on a range of different microbial communities in the future. PMID:22763648

  17. An Overview of Biomolecular Event Extraction from Scientific Documents

    PubMed Central

    Vanegas, Jorge A.; Matos, Sérgio; González, Fabio; Oliveira, José L.

    2015-01-01

    This paper presents a review of state-of-the-art approaches to automatic extraction of biomolecular events from scientific texts. Events involving biomolecules such as genes, transcription factors, or enzymes, for example, have a central role in biological processes and functions and provide valuable information for describing physiological and pathogenesis mechanisms. Event extraction from biomedical literature has a broad range of applications, including support for information retrieval, knowledge summarization, and information extraction and discovery. However, automatic event extraction is a challenging task due to the ambiguity and diversity of natural language and higher-level linguistic phenomena, such as speculations and negations, which occur in biological texts and can lead to misunderstanding or incorrect interpretation. Many strategies have been proposed in the last decade, originating from different research areas such as natural language processing, machine learning, and statistics. This review summarizes the most representative approaches in biomolecular event extraction and presents an analysis of the current state of the art and of commonly used methods, features, and tools. Finally, current research trends and future perspectives are also discussed. PMID:26587051

  18. MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations

    PubMed Central

    Vergara-Perez, Sandra; Marucho, Marcelo

    2015-01-01

    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. PMID:26924848

  19. MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations

    NASA Astrophysics Data System (ADS)

    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.

  20. Role of biomolecular logic systems in biosensors and bioactuators

    NASA Astrophysics Data System (ADS)

    Mailloux, Shay; Katz, Evgeny

    2014-09-01

    An overview of recent advances in biosensors and bioactuators based on biocomputing systems is presented. Biosensors digitally process multiple biochemical signals through Boolean logic networks of coupled biomolecular reactions and produce an output in the form of a YES/NO response. Compared to traditional single-analyte sensing devices, the biocomputing approach enables high-fidelity multianalyte biosensing, which is particularly beneficial for biomedical applications. Multisignal digital biosensors thus promise advances in rapid diagnosis and treatment of diseases by processing complex patterns of physiological biomarkers. Specifically, they can provide timely detection and alert medical personnel of medical emergencies together with immediate therapeutic intervention. Application of the biocomputing concept has been successfully demonstrated for systems performing logic analysis of biomarkers corresponding to different injuries, particularly as exemplified for liver injury. Wide-ranging applications of multianalyte digital biosensors in medicine, environmental monitoring, and homeland security are anticipated. "Smart" bioactuators, for signal-triggered drug release, for example, were designed by interfacing switchable electrodes with biocomputing systems. Integration of biosensing and bioactuating systems with biomolecular information processing systems advances the potential for further scientific innovations and various practical applications.

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

    PubMed Central

    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

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

    PubMed

    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. PMID:27108187

  3. Analysis of biomolecular interactions using affinity microcolumns: a review.

    PubMed

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

    2014-10-01

    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

  4. Biomolecular logic systems: applications to biosensors and bioactuators

    NASA Astrophysics Data System (ADS)

    Katz, Evgeny

    2014-05-01

    The paper presents an overview of recent advances in biosensors and bioactuators based on the biocomputing concept. Novel biosensors digitally process multiple biochemical signals through Boolean logic networks of coupled biomolecular reactions and produce output in the form of YES/NO response. Compared to traditional single-analyte sensing devices, biocomputing approach enables a high-fidelity multi-analyte biosensing, particularly beneficial for biomedical applications. Multi-signal digital biosensors thus promise advances in rapid diagnosis and treatment of diseases by processing complex patterns of physiological biomarkers. Specifically, they can provide timely detection and alert to medical emergencies, along with an immediate therapeutic intervention. Application of the biocomputing concept has been successfully demonstrated for systems performing logic analysis of biomarkers corresponding to different injuries, particularly exemplified for liver injury. Wide-ranging applications of multi-analyte digital biosensors in medicine, environmental monitoring and homeland security are anticipated. "Smart" bioactuators, for example for signal-triggered drug release, were designed by interfacing switchable electrodes and biocomputing systems. Integration of novel biosensing and bioactuating systems with the biomolecular information processing systems keeps promise for further scientific advances and numerous practical applications.

  5. Subfamily Limoniinae Speiser, 1909 (Diptera, Limoniidae) from Baltic Amber (Eocene): The Genus Elephantomyia Osten Sacken, 1860

    PubMed Central

    Kania, Iwona

    2015-01-01

    A revision of the genus Elephantomyia Osten Sacken (Diptera: Limoniidae) from Baltic amber (Eocene) is presented. Four species—E. baltica Alexander, E. brevipalpa Loew, E. longirostris Loew, and E. pulchella Loew—are redescribed and documented with photographs and drawings. In addition, two new species of the genus are described: Elephantomyia bozenae sp. nov., and Elephantomyia irinae sp. nov. All these fossil species are placed within the subgenus Elephantomyia. A key to the extinct species of Elephantomyia is provided, and the genus’ ecological pattern and evolutionary aspects are discussed. PMID:25706127

  6. Eonandeva gen. nov., a new distinctive genus from Eocene Baltic amber (Diptera: Chironomidae).

    PubMed

    Zakrzewska, Marta; Giłka, Wojciech

    2015-01-01

    A new fossil genus, Eonandeva gen. nov., with two new species: E. helva sp. nov. (type for the genus) and E. latistyla sp. nov., is described from Eocene Baltic amber (~45-40 Ma). Adult males of both new species show the wing venation pattern, shape and chaetotaxy typical for the tribe Tanytarsini. The characters defined as prior apomorphies for the new genus--the gonostylus with a subapical flattened lobe and the stout, strongly elongated superior volsella--separate Eonandeva from the closely related extant genus Nandeva Wiedenbrug, Reiss et Fittkau, 1998. PMID:26624727

  7. Amber from western Amazonia reveals Neotropical diversity during the middle Miocene

    PubMed Central

    Antoine, Pierre-Olivier; De Franceschi, Dario; Flynn, John J.; Nel, André; Baby, Patrice; Benammi, Mouloud; Calderón, Ysabel; Espurt, Nicolas; Goswami, Anjali; Salas-Gismondi, Rodolfo

    2006-01-01

    Tertiary insects and arachnids have been virtually unknown from the vast western Amazonian basin. We report here the discovery of amber from this region containing a diverse fossil arthropod fauna (13 hexapod families and 3 arachnid species) and abundant microfossil inclusions (pollen, spores, algae, and cyanophyceae). This unique fossil assemblage, recovered from middle Miocene deposits of northeastern Peru, greatly increases the known diversity of Cenozoic tropical–equatorial arthropods and microorganisms and provides insights into the biogeography and evolutionary history of modern Neotropical biota. It also strengthens evidence for the presence of more modern, high-diversity tropical rainforest ecosystems during the middle Miocene in western Amazonia. PMID:16950875

  8. Investigation of amber light-emitting diodes based on InGaN/AlN/AlGaN quantum wells

    NASA Astrophysics Data System (ADS)

    Iida, Daisuke; Lu, Shen; Hirahara, Sota; Niwa, Kazumasa; Kamiyama, Satoshi; Ohkawa, Kazuhiro

    2016-05-01

    We investigated InGaN-based amber light-emitting diodes (LEDs) with AlN/(Al)GaN barrier layers grown by metalorganic vapor-phase epitaxy. Tensilely strained AlN/Al0.03Ga0.97N barriers improved the crystalline quality of compressively strained InGaN quantum wells. We found that strain compensation among wells and barriers improves the external quantum efficiency of high-In-content InGaN-based amber LEDs. The amber LEDs with AlN/Al0.03Ga0.97N barriers have shown an electroluminescence (EL) intensity approximately 2.5-fold that of LEDs with the AlN/GaN barriers at 20 mA.

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

    NASA Astrophysics Data System (ADS)

    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

  10. X-ray refinement significantly underestimates the level of microscopic heterogeneity in biomolecular crystals

    PubMed Central

    Kuzmanic, Antonija; Pannu, Navraj S.; Zagrovic, Bojan

    2014-01-01

    Biomolecular X-ray structures typically provide a static, time- and ensemble-averaged view of molecular ensembles in crystals. In the absence of rigid-body motions and lattice defects, B-factors are thought to accurately reflect the structural heterogeneity of such ensembles. In order to study the effects of averaging on B-factors, we employ molecular dynamics simulations to controllably manipulate microscopic heterogeneity of a crystal containing 216 copies of villin headpiece. Using average structure factors derived from simulation, we analyse how well this heterogeneity is captured by high-resolution molecular-replacement-based model refinement. We find that both isotropic and anisotropic refined B-factors often significantly deviate from their actual values known from simulation: even at high 1.0 Å resolution and Rfree of 5.9%, B-factors of some well-resolved atoms underestimate their actual values even sixfold. Our results suggest that conformational averaging and inadequate treatment of correlated motion considerably influence estimation of microscopic heterogeneity via B-factors, and invite caution in their interpretation. PMID:24504120

  11. Benchmark Study of the SCC-DFTB Approach for a Biomolecular Proton Channel

    PubMed Central

    Liang, Ruibin; Swanson, Jessica M. J.; Voth, Gregory A.

    2014-01-01

    The self-consistent charge density functional tight binding (SCC-DFTB) method has been increasingly applied to study proton transport (PT) in biological environments. However, recent studies revealing some significant limitations of SCC-DFTB for proton and hydroxide solvation and transport in bulk aqueous systems call into question its accuracy for simulating PT in biological systems. The current work benchmarks the SCC-DFTB/MM method against more accurate DFT/MM by simulating PT in a synthetic leucine-serine channel (LS2), which emulates the structure and function of biomolecular proton channels. It is observed that SCC-DFTB/MM produces over-coordinated and less structured pore water, an over-coordinated excess proton, weak hydrogen bonds around the excess proton charge defect and qualitatively different PT dynamics. Similar issues are demonstrated for PT in a carbon nanotube, indicating that the inaccuracies found for SCC-DFTB are not due to the point charge based QM/MM electrostatic coupling scheme, but rather to the approximations of the semiempirical method itself. The results presented in this work highlight the limitations of the present form of the SCC-DFTB/MM approach for simulating PT processes in biological protein or channel-like environments, while providing benchmark results that may lead to an improvement of the underlying method. PMID:25104919

  12. A quasi non-destructive approach for amber geological provenance assessment based on head space solid-phase microextraction gas chromatography-mass spectrometry.

    PubMed

    van der Werf, I D; Aresta, A; Truică, G I; Radu, G L; Palmisano, F; Sabbatini, L

    2014-02-01

    Head space (HS) solid-phase micro-extraction (SPME) combined with gas chromatography-mass spectrometry (GC-MS) was used to analyze the volatile fraction of ambers of different geological origin. In particular, Romanian (romanite) and Baltic (succinite) amber samples were studied. Both types of amber have nearly similar bulk chemical compositions and could probably reflect only some differences of paleobiological and/or diagenetic origin. The present study shows that amber head space fingerprint, obtained by SPME/GC-MS, can provide a simple and quasi non-destructive method capable of romanite/succinite differentiation. Among the numerous compounds present in the head space, a number of few informative variables could be selected that were able to differentiate the ambers as demonstrated by Principal Component and Cluster Analysis. PMID:24401437

  13. The first Mesozoic microwhip scorpion (Palpigradi): a new genus and species in mid-Cretaceous amber from Myanmar

    NASA Astrophysics Data System (ADS)

    Engel, Michael S.; Breitkreuz, Laura C. V.; Cai, Chenyang; Alvarado, Mabel; Azar, Dany; Huang, Diying

    2016-04-01

    A fossil palpigrade is described and figured from mid-Cretaceous (Cenomanian) amber from northern Myanmar. Electrokoenenia yaksha Engel and Huang, gen. n. et sp. n., is the first Mesozoic fossil of its order and the only one known as an inclusion in amber, the only other fossil being a series of individuals encased in Pliocene onyx marble and 94-97 million years younger than E. yaksha. The genus is distinguished from other members of the order but is remarkably consistent in observable morphological details when compared to extant relatives, likely reflecting a consistent microhabitat and biological preferences over the last 100 million years.

  14. The first Mesozoic microwhip scorpion (Palpigradi): a new genus and species in mid-Cretaceous amber from Myanmar.

    PubMed

    Engel, Michael S; Breitkreuz, Laura C V; Cai, Chenyang; Alvarado, Mabel; Azar, Dany; Huang, Diying

    2016-04-01

    A fossil palpigrade is described and figured from mid-Cretaceous (Cenomanian) amber from northern Myanmar. Electrokoenenia yaksha Engel and Huang, gen. n. et sp. n., is the first Mesozoic fossil of its order and the only one known as an inclusion in amber, the only other fossil being a series of individuals encased in Pliocene onyx marble and 94-97 million years younger than E. yaksha. The genus is distinguished from other members of the order but is remarkably consistent in observable morphological details when compared to extant relatives, likely reflecting a consistent microhabitat and biological preferences over the last 100 million years. PMID:26879963

  15. Compression fossil Mymaridae (Hymenoptera) from Kishenehn oil shales, with description of two new genera and review of Tertiary amber genera

    PubMed Central

    Huber, John T.; Greenwalt, Dale

    2011-01-01

    Abstract Compression fossils of three genera and six species of Mymaridae (Hymenoptera: Chalcidoidea) are described from 46 million year old Kishenehn oil shales in Montana, USA. Two new genera are described: Eoeustochus Huber, gen. n., with two included species, Eoeustochus kishenehn Huber (type species) and Eoeustochus borchersi Huber, sp. n., and Eoanaphes, gen. n., with Eoanaphes stethynioides Huber, sp. n. Three new species of Gonatocerus are also described, Gonatocerus greenwalti Huber, sp. n. , Gonatocerus kootenai Huber, sp. n., and Gonatocerus rasnitsyni Huber, sp. n. Previously described amber fossil genera are discussed and five genera in Baltic amber are tentatively recorded as fossils: Anagroidea, Camptoptera, Dorya, Eustochus, and Mimalaptus. PMID:22259294

  16. Motional timescale predictions by molecular dynamics simulations: Case study using proline and hydroxyproline sidechain dynamics

    PubMed Central

    Aliev, Abil E; Kulke, Martin; Khaneja, Harmeet S; Chudasama, Vijay; Sheppard, Tom D; Lanigan, Rachel M

    2014-01-01

    We propose a new approach for force field optimizations which aims at reproducing dynamics characteristics using biomolecular MD simulations, in addition to improved prediction of motionally averaged structural properties available from experiment. As the source of experimental data for dynamics fittings, we use 13C NMR spin-lattice relaxation times T1 of backbone and sidechain carbons, which allow to determine correlation times of both overall molecular and intramolecular motions. For structural fittings, we use motionally averaged experimental values of NMR J couplings. The proline residue and its derivative 4-hydroxyproline with relatively simple cyclic structure and sidechain dynamics were chosen for the assessment of the new approach in this work. Initially, grid search and simplexed MD simulations identified large number of parameter sets which fit equally well experimental J couplings. Using the Arrhenius-type relationship between the force constant and the correlation time, the available MD data for a series of parameter sets were analyzed to predict the value of the force constant that best reproduces experimental timescale of the sidechain dynamics. Verification of the new force-field (termed as AMBER99SB-ILDNP) against NMR J couplings and correlation times showed consistent and significant improvements compared to the original force field in reproducing both structural and dynamics properties. The results suggest that matching experimental timescales of motions together with motionally averaged characteristics is the valid approach for force field parameter optimization. Such a comprehensive approach is not restricted to cyclic residues and can be extended to other amino acid residues, as well as to the backbone. Proteins 2014; 82:195–215. © 2013 Wiley Periodicals, Inc. PMID:23818175

  17. Electrical, spectral and optical performance of yellow-green and amber micro-pixelated InGaN light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Gong, Z.; Liu, N. Y.; Tao, Y. B.; Massoubre, D.; Xie, E. Y.; Hu, X. D.; Chen, Z. Z.; Zhang, G. Y.; Pan, Y. B.; Hao, M. S.; Watson, I. M.; Gu, E.; Dawson, M. D.

    2012-01-01

    Micro-pixelated InGaN LED arrays operating at 560 and 600 nm, respectively, are demonstrated for what the authors believe to be the first time. Such devices offer applications in areas including bioinstrumentation, visible light communications and optoelectronic tweezers. The devices reported are based on new epitaxial structures, retaining conventional (0 0 0 1) orientation, but incorporating electron reservoir layers which enhance the efficiency of radiative combination in the active regions. A measured output optical power density up to 8 W cm-2 (4.4 W cm-2) has been achieved from a representative pixel of the yellow-green (amber) LED array, substantially higher than that from conventional broad-area reference LEDs fabricated from the same wafer material. Furthermore, these micro-LEDs can sustain a high current density, up to 4.5 kA cm-2, before thermal rollover. A significant blueshift of the emission wavelength with increasing injection current is observed, however. This blueshift saturates at 45 nm (50 nm) for the yellow-green (amber) LED array, and numerical simulations have been used to gain insight into the responsible mechanisms in this microstructured format of device. In the relatively low-current-density regime (<3.5 kA cm-2) the blueshift is attributable to both the screening of the piezoelectric field by the injected carriers and the band-filling effect, whereas in the high-current regime, it is mainly due to band-filling. Further development of the epitaxial wafer material is expected to improve the current-dependent spectral stability.

  18. Amber InGaN-Based Light-Emitting Diodes Operable at High Ambient Temperatures

    NASA Astrophysics Data System (ADS)

    Mukai, Takashi; Narimatsu, Hiroki; Nakamura, Shuji

    1998-05-01

    High-efficiency amber InGaN single-quantum-well (SQW) structure light-emitting diodes (LEDs) with a luminous efficiency of 10 lm/W were developed. At a current of 20 mA, the external quantum efficiency, the output power and the emission wavelength of the amber InGaN SQW structure LEDs were 3.3%, 1.4 mW and 594 nm, respectively. The output power of InGaN LEDs was about twice as high as that of AlInGaP LEDs. There was a large difference in the temperature dependence of the output power between InGaN and AlInGaP LEDs. When the ambient temperature was increased from room temperature to 80°C, the output power of AlInGaP LEDs decreased dramatically. On the other hand, the output power of the InGaN LEDs remained almost constant.

  19. Crown Group Lejeuneaceae and Pleurocarpous Mosses in Early Eocene (Ypresian) Indian Amber

    PubMed Central

    Heinrichs, Jochen; Scheben, Armin; Bechteler, Julia; Lee, Gaik Ee; Schäfer-Verwimp, Alfons; Hedenäs, Lars; Singh, Hukam; Pócs, Tamás; Nascimbene, Paul C.; Peralta, Denilson F.; Renner, Matt; Schmidt, Alexander R.

    2016-01-01

    Cambay amber originates from the warmest period of the Eocene, which is also well known for the appearance of early angiosperm-dominated megathermal forests. The humid climate of these forests may have triggered the evolution of epiphytic lineages of bryophytes; however, early Eocene fossils of bryophytes are rare. Here, we present evidence for lejeuneoid liverworts and pleurocarpous mosses in Cambay amber. The preserved morphology of the moss fossil is inconclusive for a detailed taxonomic treatment. The liverwort fossil is, however, distinctive; its zig-zagged stems, suberect complicate-bilobed leaves, large leaf lobules, and small, deeply bifid underleaves suggest a member of Lejeuneaceae subtribe Lejeuneinae (Harpalejeunea, Lejeunea, Microlejeunea). We tested alternative classification possibilities by conducting divergence time estimates based on DNA sequence variation of Lejeuneinae using the age of the fossil for corresponding age constraints. Consideration of the fossil as a stem group member of Microlejeunea or Lejeunea resulted in an Eocene to Late Cretaceous age of the Lejeuneinae crown group. This reconstruction is in good accordance with published divergence time estimates generated without the newly presented fossil evidence. Balancing available evidence, we describe the liverwort fossil as the extinct species Microlejeunea nyiahae, representing the oldest crown group fossil of Lejeuneaceae. PMID:27244582

  20. Recognition of the amber UAG stop codon by release factor RF1

    SciTech Connect

    Korostelev, Andrei; Zhu, Jianyu; Asahara, Haruichi; Noller, Harry F.

    2010-08-23

    We report the crystal structure of a termination complex containing release factor RF1 bound to the 70S ribosome in response to an amber (UAG) codon at 3.6-{angstrom} resolution. The amber codon is recognized in the 30S subunit-decoding centre directly by conserved elements of domain 2 of RF1, including T186 of the PVT motif. Together with earlier structures, the mechanisms of recognition of all three stop codons by release factors RF1 and RF2 can now be described. Our structure confirms that the backbone amide of Q230 of the universally conserved GGQ motif is positioned to contribute directly to the catalysis of the peptidyl-tRNA hydrolysis reaction through stabilization of the leaving group and/or transition state. We also observe synthetic-negative interactions between mutations in the switch loop of RF1 and in helix 69 of 23S rRNA, revealing that these structural features interact functionally in the termination process. These findings are consistent with our proposal that structural rearrangements of RF1 and RF2 are critical to accurate translation termination.

  1. The First Ant-Termite Syninclusion in Amber with CT-Scan Analysis of Taphonomy

    PubMed Central

    Coty, David; Aria, Cédric; Garrouste, Romain; Wils, Patricia; Legendre, Frédéric; Nel, André

    2014-01-01

    We describe here a co-occurrence (i.e. a syninclusion) of ants and termites in a piece of Mexican amber (Totolapa deposit, Chiapas), whose importance is two-fold. First, this finding suggests at least a middle Miocene antiquity for the modern, though poorly documented, relationship between Azteca ants and Nasutitermes termites. Second, the presence of a Neivamyrmex army ant documents an in situ raiding behaviour of the same age and within the same community, confirmed by the fact that the army ant is holding one of the termite worker between its mandibles and by the presence of a termite with bitten abdomen. In addition, we present how CT-scan imaging can be an efficient tool to describe the topology of resin flows within amber pieces, and to point out the different states of preservation of the embedded insects. This can help achieving a better understanding of taphonomical processes, and tests ethological and ecological hypotheses in such complex syninclusions. PMID:25140873

  2. Crown Group Lejeuneaceae and Pleurocarpous Mosses in Early Eocene (Ypresian) Indian Amber.

    PubMed

    Heinrichs, Jochen; Scheben, Armin; Bechteler, Julia; Lee, Gaik Ee; Schäfer-Verwimp, Alfons; Hedenäs, Lars; Singh, Hukam; Pócs, Tamás; Nascimbene, Paul C; Peralta, Denilson F; Renner, Matt; Schmidt, Alexander R

    2016-01-01

    Cambay amber originates from the warmest period of the Eocene, which is also well known for the appearance of early angiosperm-dominated megathermal forests. The humid climate of these forests may have triggered the evolution of epiphytic lineages of bryophytes; however, early Eocene fossils of bryophytes are rare. Here, we present evidence for lejeuneoid liverworts and pleurocarpous mosses in Cambay amber. The preserved morphology of the moss fossil is inconclusive for a detailed taxonomic treatment. The liverwort fossil is, however, distinctive; its zig-zagged stems, suberect complicate-bilobed leaves, large leaf lobules, and small, deeply bifid underleaves suggest a member of Lejeuneaceae subtribe Lejeuneinae (Harpalejeunea, Lejeunea, Microlejeunea). We tested alternative classification possibilities by conducting divergence time estimates based on DNA sequence variation of Lejeuneinae using the age of the fossil for corresponding age constraints. Consideration of the fossil as a stem group member of Microlejeunea or Lejeunea resulted in an Eocene to Late Cretaceous age of the Lejeuneinae crown group. This reconstruction is in good accordance with published divergence time estimates generated without the newly presented fossil evidence. Balancing available evidence, we describe the liverwort fossil as the extinct species Microlejeunea nyiahae, representing the oldest crown group fossil of Lejeuneaceae. PMID:27244582

  3. The use of a GIS Red-Amber-Green (RAG) system to define search priorities for burials

    NASA Astrophysics Data System (ADS)

    Somma, Roberta; Silvestro, Massimiliano; Cascio, Maria; Dawson, Lorna; Donnelly, Laurance; Harrison, Mark; McKinley, Jennifer; Ruffell, Alastair

    2016-04-01

    The aim of this research is to promote among the Italian police, magistrates, and geologists, the applications of a Geographical Information System (GIS)-based RAG system for use in ground searches for burials. To date the RAG system has not been used and documented in Italy and would potentially be useful for searches related to clandestine burial sites. This technique, was originally documented by the British Army in the 1st World War. The RAG method is based on the construction of theme maps. RAG maps can facilitate the deployment of appropriate search assets (such as geophysics, probe or search dogs) and therefore applied to ground searches for the potential location of homicide graves or other buried objects (including weapons, explosives, etc.). RAG maps also may assist in the management of resources such as the deployment of search personnel, search teams and dogs. A GIS RAG (Red-Amber-Green) system related to a search for a homicide grave was applied to a test site in Italy, simulating the concealment of a victim in the area of Alì. This is an area of hill in Sicily, characterized by Palaeozoic phyllites. It was assumed during this test that information was provided by an observer who saw a suspect carrying tools on his land during daylight hours. A desktop study of the rural area was first implemented. Data was collated from previous geological, geomorphological, hydrogeological, geophysical and land use surveys. All these data were stored and independently analysed in a GIS using ArcGIS software. For the development of the GIS-based RAG map a digital elevation model (DEM) including a digital surface model (DTS) and digital terrain model (DTM) types were used. These were integrated with data from soil surveys to provide a preliminary assessment of "diggability" - including the possible thickness of loose superficial deposits and soils. Data were stored in different layers within the GIS. These included the delineation of the search area with consideration

  4. Clumpy dust clouds and extended atmosphere of the AGB star W Hydrae revealed with VLT/SPHERE-ZIMPOL and VLTI/AMBER

    NASA Astrophysics Data System (ADS)

    Ohnaka, K.; Weigelt, G.; Hofmann, K.-H.

    2016-05-01

    the prediction of the hydrodynamical models for the mass loss driven by the scattering due to micron-sized grains. The detection of the clumpy dust clouds close to the star lends support to the dust formation induced by pulsation and large convective cells as predicted by the 3D simulations for AGB stars. Based on SPHERE and AMBER observations made with the Very Large Telescope and Very Large Telescope Interferometer of the European Southern Observatory. Program ID: 095.D-0397(D) and 093.D-0468(A).

  5. Self-Assembled Biomolecular Materials Confined on Lithographic Surfaces

    NASA Astrophysics Data System (ADS)

    Pfohl, Thomas; Kim, Joon Heon; Case, Ryan; Li, Youli; Safinya, Cyrus R.

    2000-03-01

    Lithographically patterned Si-surfaces with different geometries (linear and circular channels) are used for confining and orienting assemblies of biomacromolecules. In order to direct the self assembly, the surfaces are coated with thin organic layers to change the hydrophobicity and surface charge. Droplet casting, spin coating and microinjection are used to fill the channels with biomaterials. In particular, the use of the microinjection technique allows us to control the formation of biomolecular assemblies for highly oriented x-ray samples as well as to fill single channels (width < 5μm) with dilute solutions for single molecule investigations. Biomaterials based on tubulin are our primary interest. We use fluorescence, confocal, and polarization microscopy to observe the polymerization of microtubules from tubulin and the formation of tubulin-cationic lipid complexes. Supported by NSF DMR-9972246, University of California Biotech Research, and Education Program Training Grant 99-14, DFG Pf 375/1-1.

  6. Glucose-Nucleobase Pseudo Base Pairs: Biomolecular Interactions within DNA.

    PubMed

    Vengut-Climent, Empar; Gómez-Pinto, Irene; Lucas, Ricardo; Peñalver, Pablo; Aviñó, Anna; Fonseca Guerra, Célia; Bickelhaupt, F Matthias; Eritja, Ramón; González, Carlos; Morales, Juan C

    2016-07-18

    Noncovalent forces rule the interactions between biomolecules. Inspired by a biomolecular interaction found in aminoglycoside-RNA recognition, glucose-nucleobase pairs have been examined. Deoxyoligonucleotides with a 6-deoxyglucose insertion are able to hybridize with their complementary strand, thus exhibiting a preference for purine nucleobases. Although the resulting double helices are less stable than natural ones, they present only minor local distortions. 6-Deoxyglucose stays fully integrated in the double helix and its OH groups form two hydrogen bonds with the opposing guanine. This 6-deoxyglucose-guanine pair closely resembles a purine-pyrimidine geometry. Quantum chemical calculations indicate that glucose-purine pairs are as stable as a natural T-A pair. PMID:27328804

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

    NASA Astrophysics Data System (ADS)

    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.

  8. THz time domain spectroscopy of biomolecular conformational modes.

    PubMed

    Markelz, Andrea; Whitmire, Scott; Hillebrecht, Jay; Birge, Robert

    2002-11-01

    We discuss the use of terahertz time domain spectroscopy for studies of conformational flexibility and conformational change in biomolecules. Protein structural dynamics are vital to biological function with protein flexibility affecting enzymatic reaction rates and sensory transduction cycling times. Conformational mode dynamics occur on the picosecond timescale and with the collective vibrational modes associated with these large scale structural motions in the 1-100 cm(-1) range. We have performed THz time domain spectroscopy (TTDS) of several biomolecular systems to explore the sensitivity of TTDS to distinguish different molecular species, different mutations within a single species and different conformations of a given biomolecule. We compare the measured absorbances to normal mode calculations and find that the TTDS absorbance reflects the density of normal modes determined by molecular mechanics calculations, and is sensitive to both conformation and mutation. These early studies demonstrate some of the advantages and limitations of using TTDS for the study of biomolecules. PMID:12452570

  9. The biomolecular corona of nanoparticles in circulating biological media

    NASA Astrophysics Data System (ADS)

    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

  10. Facing and Overcoming Sensitivity Challenges in Biomolecular NMR Spectroscopy.

    PubMed

    Ardenkjaer-Larsen, Jan-Henrik; Boebinger, Gregory S; Comment, Arnaud; Duckett, Simon; Edison, Arthur S; Engelke, Frank; Griesinger, Christian; Griffin, Robert G; Hilty, Christian; Maeda, Hidaeki; Parigi, Giacomo; Prisner, Thomas; Ravera, Enrico; van Bentum, Jan; Vega, Shimon; Webb, Andrew; Luchinat, Claudio; Schwalbe, Harald; Frydman, Lucio

    2015-08-01

    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 of the primary approaches that were considered. Topics discussed included the future of ultrahigh-field NMR systems, emerging NMR detection technologies, new approaches to nuclear hyperpolarization, and progress in sample preparation. All of these are orthogonal efforts, whose gains could multiply and thereby enhance the sensitivity of solid- and liquid-state experiments. While substantial advances have been made in all these areas, numerous challenges remain in the quest of endowing NMR spectroscopy with the sensitivity that has characterized forms of spectroscopies based on electrical or optical measurements. These challenges, and the ways by which scientists and engineers are striving to solve them, are also addressed. PMID:26136394

  11. Minimal metabolic pathway structure is consistent with associated biomolecular interactions

    PubMed Central

    Bordbar, Aarash; Nagarajan, Harish; Lewis, Nathan E; Latif, Haythem; Ebrahim, Ali; Federowicz, Stephen; Schellenberger, Jan; Palsson, Bernhard O

    2014-01-01

    Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we introduce an unbiased, pathway structure for genome-scale metabolic networks defined based on principles of parsimony that do not mimic canonical human-defined textbook pathways. Instead, these minimal pathways better describe multiple independent pathway-associated biomolecular interaction datasets suggesting a functional organization for metabolism based on parsimonious use of cellular components. We use the inherent predictive capability of these pathways to experimentally discover novel transcriptional regulatory interactions in Escherichia coli metabolism for three transcription factors, effectively doubling the known regulatory roles for Nac and MntR. This study suggests an underlying and fundamental principle in the evolutionary selection of pathway structures; namely, that pathways may be minimal, independent, and segregated. PMID:24987116

  12. Minimal metabolic pathway structure is consistent with associated biomolecular interactions.

    PubMed

    Bordbar, Aarash; Nagarajan, Harish; Lewis, Nathan E; Latif, Haythem; Ebrahim, Ali; Federowicz, Stephen; Schellenberger, Jan; Palsson, Bernhard O

    2014-01-01

    Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we introduce an unbiased, pathway structure for genome-scale metabolic networks defined based on principles of parsimony that do not mimic canonical human-defined textbook pathways. Instead, these minimal pathways better describe multiple independent pathway-associated biomolecular interaction datasets suggesting a functional organization for metabolism based on parsimonious use of cellular components. We use the inherent predictive capability of these pathways to experimentally discover novel transcriptional regulatory interactions in Escherichia coli metabolism for three transcription factors, effectively doubling the known regulatory roles for Nac and MntR. This study suggests an underlying and fundamental principle in the evolutionary selection of pathway structures; namely, that pathways may be minimal, independent, and segregated. PMID:24987116

  13. Nanopatterned structures for biomolecular analysis toward genomic and proteomic applications

    NASA Astrophysics Data System (ADS)

    Chou, Chia-Fu; Gu, Jian; Wei, Qihuo; Liu, Yingjie; Gupta, Ravi; Nishio, Takeyoshi; Zenhausern, Frederic

    2005-01-01

    We report our fabrication of nanoscale devices using electron beam and nanoimprint lithography (NIL). We focus our study in the emerging fields of NIL, nanophotonics and nanobiotechnology and give a few examples as to how these nanodevices may be applied toward genomic and proteomic applications for molecular analysis. The examples include reverse NIL-fabricated nanofluidic channels for DNA stretching, nanoscale molecular traps constructed from dielectric constrictions for DNA or protein focusing by dielectrophoresis, multi-layer nanoburger and nanoburger multiplets for optimized surface-plasma enhanced Raman scattering for protein detection, and biomolecular motor-based nanosystems. The development of advanced nanopatterning techniques promises reliable and high-throughput manufacturing of nanodevices which could impact significantly on the areas of genomics, proteomics, drug discovery and molecular clinical diagnostics.

  14. Calculating free-energy profiles in biomolecular systems from fast nonequilibrium processes

    NASA Astrophysics Data System (ADS)

    Forney, Michael W.; Janosi, Lorant; Kosztin, Ioan

    2008-11-01

    Often gaining insight into the functioning of biomolecular systems requires to follow their dynamics along a microscopic reaction coordinate (RC) on a macroscopic time scale, which is beyond the reach of current all atom molecular dynamics (MD) simulations. A practical approach to this inherently multiscale problem is to model the system as a fictitious overdamped Brownian particle that diffuses along the RC in the presence of an effective potential of mean force (PMF) due to the rest of the system. By employing the recently proposed FR method [I. Kosztin , J. Chem. Phys. 124, 064106 (2006)], which requires only a small number of fast nonequilibrium MD simulations of the system in both forward and time reversed directions along the RC, we reconstruct the PMF: (1) of deca-alanine as a function of its end-to-end distance, and (2) that guides the motion of potassium ions through the gramicidin A channel. In both cases the computed PMFs are found to be in good agreement with previous results obtained by different methods. Our approach appears to be about one order of magnitude faster than the other PMF calculation methods and, in addition, it also provides the position-dependent diffusion coefficient along the RC. Thus, the obtained PMF and diffusion coefficient can be used in an overdamped Brownian model to estimate important characteristics of the studied systems, e.g., the mean folding time of the stretched deca-alanine and the mean diffusion time of the potassium ion through gramicidin A.

  15. Sequence co-evolutionary information is a natural partner to minimally-frustrated models of biomolecular dynamics

    PubMed Central

    Noel, Jeffrey K; Morcos, Faruck; Onuchic, Jose N

    2016-01-01

    Experimentally derived structural constraints have been crucial to the implementation of computational models of biomolecular dynamics. For example, not only does crystallography provide essential starting points for molecular simulations but also high-resolution structures permit for parameterization of simplified models. Since the energy landscapes for proteins and other biomolecules have been shown to be minimally frustrated and therefore funneled, these structure-based models have played a major role in understanding the mechanisms governing folding and many functions of these systems. Structural information, however, may be limited in many interesting cases. Recently, the statistical analysis of residue co-evolution in families of protein sequences has provided a complementary method of discovering residue-residue contact interactions involved in functional configurations. These functional configurations are often transient and difficult to capture experimentally. Thus, co-evolutionary information can be merged with that available for experimentally characterized low free-energy structures, in order to more fully capture the true underlying biomolecular energy landscape. PMID:26918164

  16. Middle and upper cretaceous amber from the Taimyr Peninsula, Siberia: Evidence for a new structural sub-class of resinite

    SciTech Connect

    Anderson, K.B.

    1994-08-01

    Analysis of three amber (resinite) samples collected from Middle and Upper Cretaceous sediments in the Taimyr Peninsula, Siberia, indicates that these materials are based on copolymers of biformene (I) and communol (II). No resinites of similar structural character have previously been described and hence, these samples represent a previously unknown structural sub-class of resinite.

  17. A preliminary synopsis on amber scorpions with special reference to Burmite species: an extraordinary development of our knowledge in only 20 years

    PubMed Central

    Lourenço, Wilson R.

    2016-01-01

    Abstract A preliminary study on fossil scorpions found in amber, from the Lower Cretaceous through the Palaeocene and up to the Miocene is proposed. Scorpions remain rare among the arthropods found trapped in amber. Only 24 specimens are known from Cretaceous amber, representing eight families and subfamilies, ten genera and 21 species; in parallel, 10 specimens have been recorded from Baltic amber representing seven genera and ten species. A few more recent fossils from Dominican and Mexican amber have also been described. The present study of a new scorpion specimen from the Cretaceous amber of Myanmar (Burmite) resulted in the description of one new species, Betaburmesebuthus bellus sp. n. – belonging to the subfamily Palaeoburmesebuthinae Lourenço, 2015. The new description brings further elements to the clarification of the status of this subfamily, which is now raised to family level. Once again, this new Burmite element attests to the considerable degree of diversity in the Burmese amber-producing forests. PMID:27408601

  18. Evaluating time-reminder strategies before amber: common signal, green flashing and green countdown.

    PubMed

    Huang, Helai; Wang, Duo; Zheng, Liang; Li, Xiaoqing

    2014-10-01

    The safety level of signalized intersection depends greatly on drivers' decision-making behaviors, which are significantly influenced by the time-reminder strategy before amber of the signal device. However, previous related studies are mainly based on the statistical results from the field data rather than explore the influence mechanism of the signal device on the signalized intersection's safety level. Therefore, this study aims to find out how these three typical signal devices with various time-reminder strategies, i.e., common signal device (CSD), green signal flashing device (GSFD), and green signal countdown device (GSCD), affect drivers' decision-making processes during the period from the end of the green phase to the onset of the red phase (i.e., G2R) and then evaluate their safety performance from the aspect of RLR violations. Firstly, an overall decision-making framework during G2R is presented to describe the driver-signal interaction and encloses four decision-making processes, which can be analyzed and modeled based on the field data collected from six signalized intersections in Changsha, China. Empirical analyses show that the time point of decision-making before amber under GSCD is the earliest and that under CSD is the latest, which can also be modeled and reproduced by back propagation neural network (BPNN). After that, five binary logistic regression models are developed to determine the safety effect during other various processes and results show that red-light-running (RLR) violations are not only dependent on the range of dilemma zones (DZ) but also substantially on stop and go decisions of those vehicles in DZ, both of which are the potential cause and direct factors to RLR violations and found to be significantly affected by the time-reminder strategy of the green signal device. Finally, although GSCD stimulates the drivers in DZ to choose to cross the intersection during amber, which produces a higher RLR risk compared with CSD and GSFD

  19. Characterization of am404, an amber mutation in the simian virus 40 T antigen gene.

    PubMed Central

    Rawlins, D R; Collis, P; Muzyczka, N

    1983-01-01

    We analyzed the biological activity of an amber mutation, am404, at map position 0.27 in the T antigen gene of simian virus 40. Immunoprecipitation of extracts from am404-infected cells demonstrated the presence of an amber protein fragment (am T antigen) of the expected molecular weight (67,000). Differential immunoprecipitation with monoclonal antibody demonstrated that am T antigen was missing the carboxy-terminal antigenic determinants. The amber mutant was shown to be defective for most of the functions associated with wild-type T antigen. The mutant did not replicate autonomously, but this defect could be complemented by a helper virus (D. R. Rawlins and N. Muzyczka, J. Virol. 36:611-616, 1980). The mutant failed to transform nonpermissive rodent cells and did not relieve the host range restriction of adenovirus 2 in monkey cells. However, stimulation of host cell DNA, whose functional region domain has been mapped within that portion of the protein synthesized by the mutant, could be demonstrated in am404-infected cells. A number of unexpected observations were made. First, the am T antigen was produced in unusually large amounts in a simian virus 40-transformed monkey cell line (COS-1), but overproduction was not seen in nontransformed monkey cells regardless of whether or not a helper virus was present. This feature of the mutant was presumably the result of the inability of am T antigen to autoregulate, the level of wild-type T antigen in COS-1 cells, and the unusually short half-life of am T antigen in vivo. Pulse-chase experiments indicated that am T antigen had an intracellular half-life of approximately 10 min. In addition, although the am T antigen retained the major phosphorylation site found in simian virus 40 T antigen, it was not phosphorylated. Thus, phosphorylation of simian virus 40 T antigen is not required for the stimulation of host cell DNA synthesis. Finally, fusion of am404-infected monkey cells with Escherichia coli protoplasts

  20. Microbe-like inclusions in tree resins and implications for the fossil record of protists in amber.

    PubMed

    Thiel, V; Lausmaa, J; Sjövall, P; Ragazzi, E; Seyfullah, L J; Schmidt, A R

    2016-07-01

    During the past two decades, a plethora of fossil micro-organisms have been described from various Triassic to Miocene ambers. However, in addition to entrapped microbes, ambers commonly contain microscopic inclusions that sometimes resemble amoebae, ciliates, microfungi, and unicellular algae in size and shape, but do not provide further diagnostic features thereof. For a better assessment of the actual fossil record of unicellular eukaryotes in amber, we studied equivalent inclusions in modern resin of the Araucariaceae; this conifer family comprises important amber-producers in Earth history. Using time-of-flight secondary ion mass spectrometry (ToF-SIMS), we investigated the chemical nature of the inclusion matter and the resin matrix. Whereas the matrix, as expected, showed a more hydrocarbon/aromatic-dominated composition, the inclusions contain abundant salt ions and polar organics. However, the absence of signals characteristic for cellular biomass, namely distinctive proteinaceous amino acids and lipid moieties, indicates that the inclusions do not contain microbial cellular matter but salts and hydrophilic organic substances that probably derived from the plant itself. Rather than representing protists or their remains, these microbe-like inclusions, for which we propose the term 'pseudoinclusions', consist of compounds that are immiscible with the terpenoid resin matrix and were probably secreted in small amounts together with the actual resin by the plant tissue. Consequently, reports of protists from amber that are only based on the similarity of the overall shape and size to extant taxa, but do not provide relevant features at light-microscopical and ultrastructural level, cannot be accepted as unambiguous fossil evidence for these particular groups. PMID:27027519

  1. DockScreen: A database of in silico biomolecular interactions to support computational toxicology

    EPA Science Inventory

    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...

  2. Insights into molecular chemistry of Chiapas amber using infrared-light microscopy, PIXE/RBS, and sulfur K-edge XANES spectroscopy

    NASA Astrophysics Data System (ADS)

    Riquelme, Francisco; Northrup, Paul; Ruvalcaba-Sil, José Luis; Stojanoff, Vivian; Peter Siddons, D.; Alvarado-Ortega, Jesús

    2014-07-01

    Chiapas amber is a natural occurring fossil resin structurally composed of long macromolecule chains with semicrystalline phases associated with both fossil and polymerization process. The most conspicuous characteristic of this fossil polymer is that it preserves ancient organic inclusions. In the present work, PIXE/RBS spectrometry (particle-induced X-ray emission/Rutherford backscattering) were combined with complementary K-edge XANES spectroscopy (X-ray absorption near-edge structure) to identify the amount of sulfur in Chiapas amber. Initially, the amber samples were examined using infrared reflected photomicrography. Amber is transparent to infrared light and so embedded plants and animals are easily visible, showing them in extraordinary detail, as if they were immersed in a water-like solution. The PIXE/RBS data show that the proportion of sulfur in amber is significantly higher than that found in recently formed resins, consistent with the biogeochemical process that transforms the resin into amber during long-term burial in geological deposits. The sulfur K-edge XANES spectra from amber confirm the sulfur abundance and reveal sulfur species in the reduced and intermediate oxidation states in amber. Almost no oxidized sulfur was found, whereas the recent resins show mostly oxidized sulfur fractions. This indicates that labile oxidized sulfur decays during fossilization and resin maturation must occur under conditions of oxygen depletion. The implications of the presence of sulfur in amber for organic preservation is also discussed here. Sulfur compounds work as a polymer additive that promotes intense resin solidification. This restricts the early oxidant-specific biodegradation of the embedded biomatter and, over geological time, provides greater stability against chemical changes.

  3. Electrochemical Behavior of Disposable Electrodes Prepared by Ion Beam Based Surface Modification for Biomolecular Recognition

    SciTech Connect

    Erdem, A.; Karadeniz, H.; Caliskan, A.; Urkac, E. Sokullu; Oztarhan, A.; Oks, E.; Nikolayev, A.

    2009-03-10

    Many important technological advances have been made in the development of technologies to monitor interactions and recognition events of biomolecules in solution and on solid substrates. The development of advanced biosensors could impact significantly the areas of genomics, proteomics, biomedical diagnostics and drug discovery. In the literature, there have recently appeared an impressive number of intensive designs for electrochemical monitoring of biomolecular recognition. Herein, the influence of ion implanted disposable graphite electrodes on biomolecular recognition and their electrochemical behaviour was investigated.

  4. Mid-Cretaceous amber fossils illuminate the past diversity of tropical lizards.

    PubMed

    Daza, Juan D; Stanley, Edward L; Wagner, Philipp; Bauer, Aaron M; Grimaldi, David A

    2016-03-01

    Modern tropical forests harbor an enormous diversity of squamates, but fossilization in such environments is uncommon and little is known about tropical lizard assemblages of the Mesozoic. We report the oldest lizard assemblage preserved in amber, providing insight into the poorly preserved but potentially diverse mid-Cretaceous paleotropics. Twelve specimens from the Albian-Cenomanian boundary of Myanmar (99 Ma) preserve fine details of soft tissue and osteology, and high-resolution x-ray computed tomography permits detailed comparisons to extant and extinct lizards. The extraordinary preservation allows several specimens to be confidently assigned to groups including stem Gekkota and stem Chamaleonidae. Other taxa are assignable to crown clades on the basis of similar traits. The detailed preservation of osteological and soft tissue characters in these specimens may facilitate their precise phylogenetic placement, making them useful calibration points for molecular divergence time estimates and potential keys for resolving conflicts in higher-order squamate relationships. PMID:26973870

  5. Sooty moulds from European tertiary amber, with notes on the systematic position of Rosaria ('Cyanobacteria').

    PubMed

    Rikkinen, Jouko; Dörfelt, Heinrich; Schmidt, Alexander R; Wunderlich, Jörg

    2003-02-01

    Sooty moulds are described and illustrated from European amber dating back to 22-54 Myr. All the fossils are fragments of superficial subicula composed of brown moniliform hyphae with markedly tapering distal ends. The subglobose cells are identical to those of extant Metacapnodium (Metacapnodiaceae, Capnodiales) species. Also other preserved features, like the type of apical growth, wide-angled branching and the production of two distinctive conidial states, supports a placement in this genus. The fossils demonstrate that Metacapnodium hyphae have remained unchanged for tens of millions of years. This confirms that hyphal morphology and conidial states should be accorded considerable classificatory significance in this group of fungi. The following nomenclatural change is made: Metacapnodium succinum comb. nov. (syn. Rosaria succina). The type specimen was initially described as a filamentous cyanobacterium, due to similarities with Rosaria ramosa. Also the systematic position of this attribute is shortly discussed. PMID:12747338

  6. The genus Macroteleia Westwood in Middle Miocene amber from Peru (Hymenoptera, Platygastridae s.l., Scelioninae)

    PubMed Central

    Perrichot, Vincent; Antoine, Pierre-Olivier; Salas-Gismondi, Rodolfo; Flynn, John J.; Engel, Michael S.

    2014-01-01

    Abstract A new species of the scelionine genus Macroteleia Westwood (Platygastridae s.l., Scelioninae) is described and figured from a female beautifully preserved in Middle Miocene amber from Peru. Macroteleia yaguarum Perrichot & Engel, sp. n., shows a unique combination of characters otherwise seen independently within its congeners. It is most similar to the modern M. surfacei Brues, but differs from it by the non-foveolate notauli, the contiguous punctures of the vertex, and the continuous propodeum. The new species is the first New World fossil of the genus, suggesting a Cretaceous origin for the group and a relatively old age of the South American, tropical African, and Australian faunas, and a younger age of the modern Holarctic faunas. PMID:25147461

  7. Mid-Cretaceous amber fossils illuminate the past diversity of tropical lizards

    PubMed Central

    Daza, Juan D.; Stanley, Edward L.; Wagner, Philipp; Bauer, Aaron M.; Grimaldi, David A.

    2016-01-01

    Modern tropical forests harbor an enormous diversity of squamates, but fossilization in such environments is uncommon and little is known about tropical lizard assemblages of the Mesozoic. We report the oldest lizard assemblage preserved in amber, providing insight into the poorly preserved but potentially diverse mid-Cretaceous paleotropics. Twelve specimens from the Albian-Cenomanian boundary of Myanmar (99 Ma) preserve fine details of soft tissue and osteology, and high-resolution x-ray computed tomography permits detailed comparisons to extant and extinct lizards. The extraordinary preservation allows several specimens to be confidently assigned to groups including stem Gekkota and stem Chamaleonidae. Other taxa are assignable to crown clades on the basis of similar traits. The detailed preservation of osteological and soft tissue characters in these specimens may facilitate their precise phylogenetic placement, making them useful calibration points for molecular divergence time estimates and potential keys for resolving conflicts in higher-order squamate relationships. PMID:26973870

  8. Exploring the water and carbon monoxide shell around Betelgeuse with VLTI/AMBER

    NASA Astrophysics Data System (ADS)

    Montargès, M.; Kervella, P.; Perrin, G.; Ohnaka, K.

    2013-05-01

    We present the results of the analysis of our recent interferometric observations of Betelgeuse, using the AMBER instrument of the VLTI. Using the medium spectral resolution mode (R ~ 1500) we detected the presence of the water vapour and carbon monoxide (CO) molecules in the H and K bands. We also derived the photospheric angular diameter in the continuum. By analysing the depth of the molecular lines and the interferometric visibilities, we derived the column densities of the molecules, as well as the temperature and the size of the corresponding regions in the atmosphere of Betelgeuse (the MOLsphere) using a single shell model around the photosphere. Our results confirm the findings by Perrin et al. (2004) and Ohnaka et al. (2011) that the H2O and CO molecules are distributed around Betelgeuse in a MOLsphere extending to approximately 1.3 times the star's photospheric radius.

  9. Moth flies and sand flies (Diptera: Psychodidae) in Cretaceous Burmese amber

    PubMed Central

    Solórzano Kraemer, Mónica M.; Ibáñez-Bernal, Sergio; Wagner, Rüdiger

    2015-01-01

    One new subfamily, four new genera and 10 new species of Psychodidae are described from Burmese amber which significantly increases our knowledge about this group in the Cretaceous. Protopsychodinae n. subfam. probably represents the oldest known ancestor of modern Psychodinae and includes three species within two genera: Datzia setosa gen. et sp. n., Datzia bispina gen. et sp. n., and Mandalayia beumersorum gen. et sp. n. Sycoracinae and Phlebotominae are represented by two genera each in the studied material, Palaeoparasycorax globosus gen. et sp. n., Palaeoparasycorax suppus gen. et sp. n., Parasycorax simplex sp. n., and Phlebotomites aphoe sp. n. and Phlebotomus vetus sp. n., respectively. Bruchomyiinae is represented by Nemopalpus quadrispiculatus sp. n. Furthermore, one genus of an incertae sedis subfamily, Bamara groehni gen. et sp. n., is described. The systematic positions of the new taxa are discussed. PMID:26401462

  10. Aboard a spider—a complex developmental strategy fossilized in amber

    NASA Astrophysics Data System (ADS)

    Ohl, Michael

    2011-05-01

    Mantid flies (Mantispidae) are an unusual group of lacewings (Neuroptera). Adults markedly resemble mantids in their general appearance and predatory behavior. The larvae of most mantispids exclusively prey on spider eggs, whereby the first instar larva is highly mobile and active and the other two larval stages immobile and maggot like. One of the larval strategies to pursue spider eggs is spider-boarding. Here, I report on the first record of a fossil mantispid larva. It was found in Middle Eocene Baltic amber, and it is the first record of Mantispidae from this deposit. The larva is attached to a clubionoid spider in a position typical for most mantispid larvae, and, thus, it is also the first fossil record of this complex larval behavior and development.

  11. X-shooter, NACO, and AMBER observations of the LBV Pistol Star

    NASA Astrophysics Data System (ADS)

    Martayan, C.; Blomme, R.; Le Bouquin, J.-B.; Merand, A.; Montagnier, G.; Selman, F.; Girard, J.; Fox, A.; Baade, D.; Frémat, Y.; Lobel, A.; Martins, F.; Patru, F.; Rivinius, T.; Sana, H.; Stefl, S.; Zorec, J.; Semaan, T.

    2011-01-01

    We present multi-instrument and multi-wavelength observations of the famous LBV star Pistol Star. These observations are part of a larger program on early O stars at different metallicities. The Pistol Star has been claimed to be one of the most massive star known, with 250 solar masses. We present preliminary results based on X-shooter spectra, as well as observations performed with the VLTI-AMBER and the VLT-NACO adaptive optics. The X-shooter spectrograph provides simultaneously a spectrum from the UV to the K-band with a resolving power of ˜15000. The preliminary results obtained indicate that Pistol Star has similar properties to η Car, including shells of matter, but is also a binary.

  12. New earwigs in mid-Cretaceous amber from Myanmar (Dermaptera, Neodermaptera)

    PubMed Central

    Engel, Michael S.

    2011-01-01

    Abstract Two new earwigs (Dermaptera) recently discovered in mid-Cretaceous (latest Albian) amber from Myanmar are described and figured. Astreptolabis ethirosomatia gen. et sp. n. is represented by a peculiar pygidicranoid female, assigned to a new subfamily, Astreptolabidinae subfam. n., and differs from other protodermapterans in the structure of the head, pronotum, tegmina, and cercal forceps. Tytthodiplatys mecynocercus gen. et sp. n. is a distinctive form of first-instar nymph of the Diplatyidae, the earliest record for this basal earwig family. The taxon can be distinguished from other Early Cretaceous nymphs by the structure of the head, antennae, legs, and most notably its filamentous and annulate cerci. The character affinities of these taxa among Neodermaptera are generally discussed as is the identity of an enigmatic ‘earwig-like’ species from the Jurassic of China. PMID:22259272

  13. Selection of tRNA(Asp) amber suppressor mutants having alanine, arginine, glutamine, and lysine identity.

    PubMed Central

    Martin, F; Reinbolt, J; Dirheimer, G; Gangloff, J; Eriani, G

    1996-01-01

    Elements that confer identity to a tRNA in the cellular environment, where all aminoacyl-tRNA synthetases are competing for substrates, may be delineated by in vivo experiments using suppressor tRNAs. Here we describe the selection of active Escherichia coli tRNAAsp amber mutants and analyze their identity. Starting from a library containing randomly mutated tRNA(CUA)Asp genes, we isolated four amber suppressors presenting either lysine, alanine, or glutamine activity. Two of them, presenting mainly alanine or lysine activity, were further submitted to a second round of mutagenesis selection in order to improve their efficiency of suppression. Eleven suppressors were isolated, each containing two or three mutations. Ten presented identities of the two parental mutants, whereas one had switched from lysine to arginine identity. Analysis of the different mutants revealed (or confirmed for some nucleotides) their role as positive and/or negative determinants in AlaRS, LysRS, and ArgRS recognition. More generally, it appears that tRNAAsp presents identity characteristics closely related to those of tRNALys, as well as a structural basis for acquiring alanine or arginine identity upon moderate mutational changes; these consist of addition or suppression of the corresponding positive or negative determinants, as well as tertiary interactions. Failure to isolate aspartic acid-inserting suppressors is probably due to elimination of the important G34 identity element and its replacement by an antideterminant when changing the anticodon of the tRNAAsp to the CUA triplet. PMID:8809018

  14. A formicine in New Jersey Cretaceous amber (Hymenoptera: Formicidae) and early evolution of the ants

    PubMed Central

    Grimaldi, David; Agosti, Donat

    2000-01-01

    A worker ant preserved with microscopic detail has been discovered in Turonian-aged New Jersey amber [ca. 92 mega-annum (Ma)]. The apex of the gaster has an acidopore and, thus, allows definitive assignment of the fossil to the large extant subfamily Formicinae, members of which use a defensive spray of formic acid. This specimen is the only Cretaceous record of the subfamily, and only two other fossil ants are known from the Cretaceous that unequivocally belong to an extant subfamily (Brownimecia and Canapone of the Ponerinae, in New Jersey and Canadian amber, respectively). In lieu of a cladogram of formicine genera, generalized morphology of this fossil suggests a basal position in the subfamily. Formicinae and Ponerinae in the mid Cretaceous indicate divergence of basal lineages of ants near the Albian (ca. 105–110 Ma) when they presumably diverged from the Sphecomyrminae. Sphecomyrmines are the plesiomorphic sister group to all other ants, or they are a paraphyletic stem group ancestral to all other ants—they apparently became extinct in the Late Cretaceous. Ant abundance in major deposits of Cretaceous and Tertiary insects indicates that they did not become common and presumably dominant in terrestrial ecosystems until the Eocene (ca. 45 Ma). It is at this time that modern genera that form very large colonies (at least 10,000 individuals) first appear. During the Cretaceous, eusocial termites, bees, and vespid wasps also first appear—they show a similar pattern of diversification and proliferation in the Tertiary. The Cretaceous ants have further implications for interpreting distributions of modern ants. PMID:11078527

  15. Biomolecular detection employing the Interferometric Reflectance Imaging Sensor (IRIS).

    PubMed

    Lopez, Carlos A; Daaboul, George G; Ahn, Sunmin; Reddington, Alexander P; Monroe, Margo R; Zhang, Xirui; Irani, Rostem J; Yu, Chunxiao; Genco, Caroline A; Cretich, Marina; Chiari, Marcella; Goldberg, Bennett B; Connor, John H; Ünlü, M Selim

    2011-01-01

    The sensitive measurement of biomolecular interactions has use in many fields and industries such as basic biology and microbiology, environmental/agricultural/biodefense monitoring, nanobiotechnology, and more. For diagnostic applications, monitoring (detecting) the presence, absence, or abnormal expression of targeted proteomic or genomic biomarkers found in patient samples can be used to determine treatment approaches or therapy efficacy. In the research arena, information on molecular affinities and specificities are useful for fully characterizing the systems under investigation. Many of the current systems employed to determine molecular concentrations or affinities rely on the use of labels. Examples of these systems include immunoassays such as the enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR) techniques, gel electrophoresis assays, and mass spectrometry (MS). Generally, these labels are fluorescent, radiological, or colorimetric in nature and are directly or indirectly attached to the molecular target of interest. Though the use of labels is widely accepted and has some benefits, there are drawbacks which are stimulating the development of new label-free methods for measuring these interactions. These drawbacks include practical facets such as increased assay cost, reagent lifespan and usability, storage and safety concerns, wasted time and effort in labelling, and variability among the different reagents due to the labelling processes or labels themselves. On a scientific research basis, the use of these labels can also introduce difficulties such as concerns with effects on protein functionality/structure due to the presence of the attached labels and the inability to directly measure the interactions in real time. Presented here is the use of a new label-free optical biosensor that is amenable to microarray studies, termed the Interferometric Reflectance Imaging Sensor (IRIS), for detecting proteins, DNA, antigenic material

  16. Spatially-Interactive Biomolecular Networks Organized by Nucleic Acid Nanostructures

    PubMed Central

    Fu, Jinglin; Liu, Minghui; Liu, Yan; Yan, Hao

    2013-01-01

    Conspectus Living systems have evolved a variety of nanostructures to control the molecular interactions that mediate many functions including the recognition of targets by receptors, the binding of enzymes to substrates, and the regulation of enzymatic activity. Mimicking these structures outside of the cell requires methods that offer nanoscale control over the organization of individual network components. Advances in DNA nanotechnology have enabled the design and fabrication of sophisticated one-, two- and three-dimensional (1D, 2D and 3D) nanostructures that utilize spontaneous and sequence specific DNA hybridization. Compared to other self-assembling biopolymers, DNA nanostructures offer predictable and programmable interactions, and surface features to which other nanoparticles and bio-molecules can be precisely positioned. The ability to control the spatial arrangement of the components while constructing highly-organized networks will lead to various applications of these systems. For example, DNA nanoarrays with surface displays of molecular probes can sense noncovalent hybridization interactions with DNA, RNA, and proteins and covalent chemical reactions. DNA nanostructures can also align external molecules into well-defined arrays, which may improve the resolution of many structural determination methods, such as X-ray diffraction, cryo-EM, NMR, and super-resolution fluorescence. Moreover, by constraining target entities to specific conformations, self-assembled DNA nanostructures can serve as molecular rulers to evaluate conformation-dependent activities. This Account describes the most recent advances in the DNA nanostructure directed assembly of biomolecular networks and explores the possibility of applying this technology to other fields of study. Recently, several reports have demonstrated the DNA nanostructure directed assembly of spatially-interactive biomolecular networks. For example, researchers have constructed synthetic multi-enzyme cascades

  17. PARENT: A Parallel Software Suite for the Calculation of Configurational Entropy in Biomolecular Systems.

    PubMed

    Fleck, Markus; Polyansky, Anton A; Zagrovic, Bojan

    2016-04-12

    Accurate estimation of configurational entropy from the in silico-generated biomolecular ensembles, e.g., from molecular dynamics (MD) trajectories, is dependent strongly on exhaustive sampling for physical reasons. This, however, creates a major computational problem for the subsequent estimation of configurational entropy using the Maximum Information Spanning Tree (MIST) or Mutual Information Expansion (MIE) approaches for internal molecular coordinates. In particular, the available software for such estimation exhibits serious limitations when it comes to molecules with hundreds or thousands of atoms, because of its reliance on a serial program architecture. To overcome this problem, we have developed a parallel, hybrid MPI/openMP C++ implementation of MIST and MIE, called PARENT, which is particularly optimized for high-performance computing and provides efficient estimation of configurational entropy in different biological processes (e.g., protein-protein interactions). In addition, PARENT also allows for a detailed mapping of intramolecular allosteric networks. Here, we benchmark the program on a set of 1-μs-long MD trajectories of 10 different protein complexes and their components, demonstrating robustness and good scalability. A direct comparison between MIST and MIE on the same dataset demonstrates a superior convergence behavior for the former approach, when it comes to total simulation length and configurational-space binning. PMID:26989950

  18. An Atomic Force Microscope with Dual Actuation Capability for Biomolecular Experiments

    NASA Astrophysics Data System (ADS)

    Sevim, Semih; Shamsudhin, Naveen; Ozer, Sevil; Feng, Luying; Fakhraee, Arielle; Ergeneman, Olgaç; Pané, Salvador; Nelson, Bradley J.; Torun, Hamdi

    2016-06-01

    We report a modular atomic force microscope (AFM) design for biomolecular experiments. The AFM head uses readily available components and incorporates deflection-based optics and a piezotube-based cantilever actuator. Jetted-polymers have been used in the mechanical assembly, which allows rapid manufacturing. In addition, a FeCo-tipped electromagnet provides high-force cantilever actuation with vertical magnetic fields up to 0.55 T. Magnetic field calibration has been performed with a micro-hall sensor, which corresponds well with results from finite element magnetostatics simulations. An integrated force resolution of 1.82 and 2.98 pN, in air and in DI water, respectively was achieved in 1 kHz bandwidth with commercially available cantilevers made of Silicon Nitride. The controller and user interface are implemented on modular hardware to ensure scalability. The AFM can be operated in different modes, such as molecular pulling or force-clamp, by actuating the cantilever with the available actuators. The electromagnetic and piezoelectric actuation capabilities have been demonstrated in unbinding experiments of the biotin-streptavidin complex.

  19. An Atomic Force Microscope with Dual Actuation Capability for Biomolecular Experiments.

    PubMed

    Sevim, Semih; Shamsudhin, Naveen; Ozer, Sevil; Feng, Luying; Fakhraee, Arielle; Ergeneman, Olgaç; Pané, Salvador; Nelson, Bradley J; Torun, Hamdi

    2016-01-01

    We report a modular atomic force microscope (AFM) design for biomolecular experiments. The AFM head uses readily available components and incorporates deflection-based optics and a piezotube-based cantilever actuator. Jetted-polymers have been used in the mechanical assembly, which allows rapid manufacturing. In addition, a FeCo-tipped electromagnet provides high-force cantilever actuation with vertical magnetic fields up to 0.55 T. Magnetic field calibration has been performed with a micro-hall sensor, which corresponds well with results from finite element magnetostatics simulations. An integrated force resolution of 1.82 and 2.98 pN, in air and in DI water, respectively was achieved in 1 kHz bandwidth with commercially available cantilevers made of Silicon Nitride. The controller and user interface are implemented on modular hardware to ensure scalability. The AFM can be operated in different modes, such as molecular pulling or force-clamp, by actuating the cantilever with the available actuators. The electromagnetic and piezoelectric actuation capabilities have been demonstrated in unbinding experiments of the biotin-streptavidin complex. PMID:27273214

  20. An Atomic Force Microscope with Dual Actuation Capability for Biomolecular Experiments

    PubMed Central

    Sevim, Semih; Shamsudhin, Naveen; Ozer, Sevil; Feng, Luying; Fakhraee, Arielle; Ergeneman, Olgaç; Pané, Salvador; Nelson, Bradley J.; Torun, Hamdi

    2016-01-01

    We report a modular atomic force microscope (AFM) design for biomolecular experiments. The AFM head uses readily available components and incorporates deflection-based optics and a piezotube-based cantilever actuator. Jetted-polymers have been used in the mechanical assembly, which allows rapid manufacturing. In addition, a FeCo-tipped electromagnet provides high-force cantilever actuation with vertical magnetic fields up to 0.55 T. Magnetic field calibration has been performed with a micro-hall sensor, which corresponds well with results from finite element magnetostatics simulations. An integrated force resolution of 1.82 and 2.98 pN, in air and in DI water, respectively was achieved in 1 kHz bandwidth with commercially available cantilevers made of Silicon Nitride. The controller and user interface are implemented on modular hardware to ensure scalability. The AFM can be operated in different modes, such as molecular pulling or force-clamp, by actuating the cantilever with the available actuators. The electromagnetic and piezoelectric actuation capabilities have been demonstrated in unbinding experiments of the biotin-streptavidin complex. PMID:27273214

  1. Re-exploration of the Codon Context Effect on Amber Codon-Guided Incorporation of Noncanonical Amino Acids in Escherichia coli by the Blue-White Screening Assay.

    PubMed

    Xu, Huan; Wang, Yan; Lu, Jiaqi; Zhang, Bo; Zhang, Ziwei; Si, Longlong; Wu, Ling; Yao, Tianzhuo; Zhang, Chuanling; Xiao, Sulong; Zhang, Lihe; Xia, Qing; Zhou, Demin

    2016-07-01

    The effect of codon context on amber codon-guided incorporation of noncanonical amino acids (NAAs) has been previously examined by antibiotic selection. Here, we re-explored this effect by screening a library in which three nucleotides upstream and downstream of the amber codon were randomised, and inserted within the lacZ-α gene. Thousands of clones were obtained and distinguished by the depth of blue colour upon exposure to X-gal. Large-scale sequencing revealed remarkable preferences in nucleotides downstream of the amber codon, and moderate preferences for upstream nucleotides. Nucleotide preference was quantified by a dual-luciferase assay, which verified that the optimum context for NAA incorporation, AATTAGACT, was applicable to different proteins. Our work provides a general guide for engineering amber codons into genes of interest in bacteria. PMID:27028123

  2. The nature and fate of natural resins in the geosphere. XI.{sup +} ruthenium tetroxide oxidation in a mature class Ib amber polymer.

    SciTech Connect

    Anderson, K. B.; Chemistry

    2001-01-01

    The results of ruthenium tetroxide (RuO{sub 4}) oxidation of a mature Class Ib amber polymer are reported and discussed. These data indicate that the residual double bond present in mature Class I ambers is not located in the A/B ring structure of these materials and that C17 of the original labdanoid precursors is retained in mature Class I ambers as a methyl group. These data also suggest that the reaction which results in formation of the residual unsaturated structure in mature ambers also results in a second covalent connection between the A/B ring system and the polymer backbone, probably through C8 of the original labdanoid structure.

  3. Parallel biomolecular computation on surfaces with advanced finite automata.

    PubMed

    Soreni, Michal; Yogev, Sivan; Kossoy, Elizaveta; Shoham, Yuval; Keinan, Ehud

    2005-03-23

    A biomolecular, programmable 3-symbol-3-state finite automaton is reported. This automaton computes autonomously with all of its components, including hardware, software, input, and output being biomolecules mixed together in solution. The hardware consisted of two enzymes: an endonuclease, BbvI, and T4 DNA ligase. The software (transition rules represented by transition molecules) and the input were double-stranded (ds) DNA oligomers. Computation was carried out by autonomous processing of the input molecules via repetitive cycles of restriction, hybridization, and ligation reactions to produce a final-state output in the form of a dsDNA molecule. The 3-symbol-3-state deterministic automaton is an extension of the 2-symbol-2-state automaton previously reported, and theoretically it can be further expanded to a 37-symbol-3-state automaton. The applicability of this design was further amplified by employing surface-anchored input molecules, using the surface plasmon resonance technology to monitor the computation steps in real time. Computation was performed by alternating the feed solutions between endonuclease and a solution containing the ligase, ATP, and appropriate transition molecules. The output detection involved final ligation with one of three soluble detection molecules. Parallel computation and stepwise detection were carried out automatically with a Biacore chip that was loaded with four different inputs. PMID:15771530

  4. Dose controlled low energy electron irradiator for biomolecular films

    NASA Astrophysics Data System (ADS)

    Kumar, S. V. K.; Tare, Satej T.; Upalekar, Yogesh V.; Tsering, Thupten

    2016-03-01

    We have developed a multi target, Low Energy Electron (LEE), precise dose controlled irradiator for biomolecular films. Up to seven samples can be irradiated one after another at any preset electron energy and dose under UHV conditions without venting the chamber. In addition, one more sample goes through all the steps except irradiation, which can be used as control for comparison with the irradiated samples. All the samples are protected against stray electron irradiation by biasing them at -20 V during the entire period, except during irradiation. Ethernet based communication electronics hardware, LEE beam control electronics and computer interface were developed in house. The user Graphical User Interface to control the irradiation and dose measurement was developed using National Instruments Lab Windows CVI. The working and reliability of the dose controlled irradiator has been fully tested over the electron energy range of 0.5 to 500 eV by studying LEE induced single strand breaks to ΦX174 RF1 dsDNA.

  5. Electron interactions with positively and negatively multiply charged biomolecular clusters

    NASA Astrophysics Data System (ADS)

    Feketeová, Linda

    2012-07-01

    Interactions of positively and negatively multiply charged biomolecular clusters with low-energy electrons, from ~ 0 up to 50 eV of electron energy, were investigated in a high resolution Fourier-Transform Ion Cyclotron Resonance mass spectrometer equipped with an electrospray ionisation source. Electron-induced dissociation reactions of these clusters depend on the energy of the electrons, the size and the charge state of the cluster. The positively charged clusters [Mn+2H]2+ of zwitterionic betaines, M = (CH3)2XCH2CO2 (X = NCH3 and S), do capture an electron in the low electron energy region (< 10 eV). At higher electron energies neutral evaporation from the cluster becomes competitive with Coulomb explosion. In addition, a series of singly charged fragments arise from bond cleavage reactions, including decarboxylation and CH3 group transfer, due to the access of electronic excited states of the precursor ions. These fragmentation reactions depend on the type of betaine (X = NCH3 or S). For the negative dianionic clusters of tryptophan [Trp9-2H]2-, the important channel at low electron energies is loss of a neutral. Coulomb explosion competes from 19.8 eV and dominates at high electron energies. A small amount of [Trp2-H-NH3]- is observed at 21.8 eV.

  6. A programmable biomolecular computing machine with bacterial phenotype output.

    PubMed

    Kossoy, Elizaveta; Lavid, Noa; Soreni-Harari, Michal; Shoham, Yuval; Keinan, Ehud

    2007-07-23

    The main advantage of autonomous biomolecular computing devices over electronic computers is their ability to interact directly with biological systems. No interface is required since all components of molecular computers, including hardware, software, input, and output are molecules that interact in solution along a cascade of programmable chemical events. Here, we demonstrate for the first time that the output of a computation preduced by a molecular finite automaton can be a visible bacterial phenotype. Our 2-symbol-2-state finite automaton utilized linear double-stranded DNA inputs that were prepared by inserting a string of six base pair symbols into the lacZ gene on the pUC18 plasmid. The computation resulted in a circular plasmid that differed from the original pUC18 by either a 9 base pair (accepting state) or 11 base pair insert (unaccepting state) within the lacZ alpha region gene. Upon transformation and expression of the resultant plasmids in E. coli, the accepting state was represented by production of functional beta-galactosidase and formation of blue colonies on X-gal medium. In contrast, the unaccepting state was represented by white colonies due to a shift in the open reading frame of lacZ. PMID:17562552

  7. Self-assembling biomolecular catalysts for hydrogen production

    NASA Astrophysics Data System (ADS)

    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.

  8. Nanotemplated polyelectrolyte films as porous biomolecular delivery systems

    PubMed Central

    Gand, Adeline; Hindié, Mathilde; Chacon, Diane; van Tassel, Paul R; Pauthe, Emmanuel

    2014-01-01

    Biomaterials capable of delivering controlled quantities of bioactive agents, while maintaining mechanical integrity, are needed for a variety of cell contacting applications. We describe here a nanotemplating strategy toward porous, polyelectrolyte-based thin films capable of controlled biomolecular loading and release. Films are formed via the layer-by-layer assembly of charged polymers and nanoparticles (NP), then chemically cross-linked to increase mechanical rigidity and stability, and finally exposed to tetrahydrofuran to dissolve the NP and create an intra-film porous network. We report here on the loading and release of the growth factor bone morphogenetic protein 2 (BMP-2), and the influence of BMP-2 loaded films on contacting murine C2C12 myoblasts. We observe nanotemplating to enable stable BMP-2 loading throughout the thickness of the film, and find the nanotemplated film to exhibit comparable cell adhesion, and enhanced cell differentiation, compared with a non-porous cross-linked film (where BMP-2 loading is mainly confined to the film surface). PMID:25482416

  9. Function of Amphiphilic Biomolecular Machines: Elastic Protein-based Polymers

    NASA Astrophysics Data System (ADS)

    Urry, Dan W.

    2000-03-01

    Elastic protein-based polymers function as biomolecular machines due to inverse temperature transitions of hydrophobic folding and assembly. The transitions occur either on raising the temperature from below to above the transition temperature, Tt, or on isothermally lowering Tt from above to below an operating temperature. The inverse temperature transition involves a decrease in entropy of the polymer component of the system on raising the temperature and a larger increase in solvent entropy on hydrophobic association. Tt depends on the quantity of hydrophobic hydration that undergoes transition to bulk water. Designed amphiphilic polymers perform free energy transductions involving the intensive variables of mechanical force, pressure, temperature, chemical potential, electrochemical potential and electromagnetic radiation and define a set of five axioms for their function as machines. The physical basis for these diverse energy conversions is competition for hydration between apolar (hydrophobic) and polar (e.g., charged) moieties. The effectiveness of these Tt-type entropic elastic protein-based machines is due to repeating peptide sequences that form regular, dynamic repeating structures and exhibit damping of backbone torsional oscillations on extension.

  10. SWISS-PROT: connecting biomolecular knowledge via a protein database.

    PubMed

    Gasteiger, E; Jung, E; Bairoch, A

    2001-07-01

    With the explosive growth of biological data, the development of new means of data storage was needed. More and more often biological information is no longer published in the conventional way via a publication in a scientific journal, but only deposited into a database. In the last two decades these databases have become essential tools for researchers in biological sciences. Biological databases can be classified according to the type of information they contain. There are basically three types of sequence-related databases (nucleic acid sequences, protein sequences and protein tertiary structures) as well as various specialized data collections. It is important to provide the users of biomolecular databases with a degree of integration between these databases as by nature all of these databases are connected in a scientific sense and each one of them is an important piece to biological complexity. In this review we will highlight our effort in connecting biological information as demonstrated in the SWISS-PROT protein database. PMID:11488411

  11. Effects of Clear and Amber Cullet on Physical and Mechanical Properties of Glass-Ceramics Containing Zinc Hydrometallurgy Waste

    NASA Astrophysics Data System (ADS)

    Hanpongpun, Wilasinee; Jiemsirilers, Sirithan; Thavorniti, Parjaree

    The effect of glass cullet on physical and mechanical properties of glass-ceramics developed from zinc hydrometallurgy waste and glass cullet was investigated. The glass-ceramics were prepared by mixing zinc hydrometallurgy waste with glass cullet through vitrification process. Two difference types of glass cullet (clear and amber cullet) were used. The parent glasses were ground and pressed into bars and sintered at low temperature (850°C) for 2 hours. The obtained glass-ceramics had low porosity. The glass-ceramics with clear cullet exhibited higher density and strength, comparing with the glass-ceramics with amber cullet. The type and the amount of the glass cullet present in the glass-ceramics have strong effect on their properties.

  12. A new genus and species of the paraneopteran family Archipsyllidae in mid-Cretaceous amber of Myanmar.

    PubMed

    Liang, Feiyang; Zhang, Weiwei; Liu, Xingyue

    2016-01-01

    Paraneoptera is a group of orders, representing one of the highly diverse clades of winged insects. Paleozoic and Mesozoic fossil paraneopterans include a few primitive species, which are significant for understanding the early evolution of Paraneoptera. Here we report a new genus and species, namely Burmopsylla maculata gen. et sp. nov. from the mid-Cretaceous (ca. 99 Myr) amber of Myanmar. The new genus belongs to the family Archipsyllidae by having hindwing similar to forewing (shape, size and venation), presence of forewing ra-rp, rp-m and cua-cup crossveins, two-branched R, four-branched M, and four-segmented tarsus. The new species represents the second species of Archipsyllidae in Cretaceous Burmese amber. PMID:27394792

  13. Cellular fine structures and histochemical reactions in the tissue of a cypress twig preserved in Baltic amber

    PubMed Central

    Koller, Barbara; Schmitt, Jürgen M.; Tischendorf, Gilbert

    2005-01-01

    A twig of a cypress plant preserved for ca. 45Myr in Baltic amber was analysed by light and electron microscopy. Cross-sections of the whole plant showed an almost intact tissue of the entire stem and leaves, revealing, to our knowledge, the oldest and most highly preserved tissue from an amber inclusion reported so far. The preparations are based on a new technique of internal imbedding, whereby the hollow spaces within the inclusion are filled with synthetic resin which stabilizes the cellular structures during the sectioning procedure. Cytological stains applied to the sections reacted with cell walls and nuclei. A strong green auto-fluorescence of the cuticle and the resin canals in the leaves was observed. Transmission electron micrographs revealed highly preserved fine structures of cell walls, membranes and organelles. The results were compared with taxonomically related recent Glyptostrobus and Juniperus plants. PMID:15695201

  14. Genetic selection for active E.coli amber tRNA(Asn) exclusively led to glutamine inserting suppressors.

    PubMed Central

    Martin, F; Eriani, G; Reinbolt, J; Dirheimer, G; Gangloff, J

    1995-01-01

    Suppressor tRNAs are useful tools for determining identity elements which define recognition of tRNAs in vivo by their cognate aminoacyl-tRNA synthetases. This study was aimed at the isolation of active amber tRNA(Asn). Nineteen mutated tRNA(Asn)CUA having amber suppressor activity were selected by an in vivo genetic screen, and all exclusively inserted glutamine. From analysis of the different mutations it is concluded that glutamine accepting activity was obtained upon reducing the interaction strength between the first base pair of the tRNA(Asn)CUA by direct or indirect effects. Failure to isolate tRNA(Asn)CUA suppressors charged with asparagine as well as other evolutionary related amino acids is discussed. PMID:7708493

  15. Kujigamberol, a new dinorlabdane diterpenoid isolated from 85million years old Kuji amber using a biotechnological assay.

    PubMed

    Kimura, Ken-ichi; Minamikawa, Yuki; Ogasawara, Yukiko; Yoshida, Jun; Saitoh, Kei-ichi; Shinden, Hisao; Ye, Yue Qi; Takahashi, Shunya; Miyakawa, Tokichi; Koshino, Hiroyuki

    2012-07-01

    A new compound, 15,20-dinor-5,7,9-labdatriene-18-ol (1), named kujigamberol, was isolated from amber, fossilized tree resin from the Kuji area in Japan, has been dated as being 85 million years old (late Cretaceous). Kujigamberol was identified using the hypersensitive mutant yeast (zds1∆ erg3∆ pdr1∆ pdr3∆) with respect to Ca(2+)-signal transduction. The structure was elucidated on the basis of spectroscopic analysis including 1D NMR, 2D NMR and HR-EI-MS. It was different from known diterpenoids with a similar activity isolated from Baltic amber (agathic acid 15-monomethyl ester (2), dehydroabietic acid (3) and pimaric acid (4)). Kujigamberol showed glycogen synthase kinase-3β (GSK-3β) inhibition activity involving the growth restored activity against the mutant yeast and was cytotoxic to HL60 cells (IC(50)=19.6 μM). PMID:22507387

  16. A new genus and species of micro bee fly from the Earliest Eocene French amber (Diptera: Mythicomyiidae: Psiloderoidinae).

    PubMed

    Myskowiak, Justine; Garrouste, Romain; Nel, Andre

    2016-01-01

    Mythicomyiidae, or micro bee flies, are tiny flies (0.5-5.0 mm) that are found throughout most parts of the world except the highest altitudes and latitudes (Greathead & Evenhuis 2001). Including all extinct and extant taxa, the Mythicomyiidae currently comprise more than 380 valid taxonomic species distributed among 30 genera. The subfamily Psiloderoidinae is especially well represented among the fossil Mythicomyiidae by seven Cretaceous or Cenozoic genera. We here describe a new genus and a new species of this subfamily based on fossils from the Earliest Eocene of Oise (France). A Psiloderoidinae, Proplatypygus matilei Nel & DePloëg, 2004, is already described in this amber. Another mythicomyiid, Eurodoliopteryx inexpectatus Nel, 2006, is the most frequent bombylioid in this amber (Nel & DePloëg, 2004; Nel, 2006). PMID:27395149

  17. Assessing the accuracy of the general AMBER force field for 2,2,2-trifluoroethanol as solvent.

    PubMed

    Jia, Xiangyu; Zhang, John Z H; Mei, Ye

    2013-06-01

    The alcohol-based cosolvent 2,2,2-trifluoroethanol (TFE) has been used widely in protein science and engineering. Many experimental and computational studies of its impact on protein structure have been carried out, but consensus on the mechanism has not been reached. In the past decade, several molecular mechanical models have been proposed to model the structure and dynamics of TFE. However, further calibration is still necessary. In particular, its compatibility with protein force fields has not been well examined. The general AMBER force field (GAFF) has proved quite successful in modeling small organic molecules, and is compatible with contemporary AMBER force field. In this work, we assessed the accuracy of GAFF for the TFE molecule as a bulk solvent. Several properties, such as density, dipole moment, radial distribution function, etc., were calculated and compared with experimental data. The results show that GAFF plays fairly well in the description of bulk TFE, although there is still room for improvement. PMID:23397068

  18. Two-level systems and boson peak remain stable in 110-million-year-old amber glass.

    PubMed

    Pérez-Castañeda, Tomás; Jiménez-Riobóo, Rafael J; Ramos, Miguel A

    2014-04-25

    The two most prominent and ubiquitous features of glasses at low temperatures, namely the presence of tunneling two-level systems and the so-called boson peak in the reduced vibrational density of states, are shown to persist essentially unchanged in highly stabilized glasses, contrary to what was usually envisaged. Specifically, we have measured the specific heat of 110 million-year-old amber samples from El Soplao (Spain), both at very low temperatures and around the glass transition Tg. In particular, the amount of two-level systems, assessed at the lowest temperatures, was surprisingly found to be exactly the same for the pristine hyperaged amber as for the, subsequently, partially and fully rejuvenated samples. PMID:24815658

  19. The first fossil record of the Emesinae genus Emesopsis Uhler (Hemiptera: Heteroptera, Reduviidae) from Eocene Baltic amber.

    PubMed

    Popov, Yuri A; Chłond, Dominik

    2015-01-01

    Two new fossil representatives of the assassin bug family Reduviidae are described as new from Baltic amber (Upper Eocene), belonging to the genus Emesopsis of the tribe Ploiariolini (Emesinae): Emesopsis putshkovi sp. nov. and E. similis sp. nov. These representatives of the Emesinae are the oldest fossil bugs of the genus Emesopsis known so far, and reported for the first time. This genus is also briefly diagnosed. PMID:26624642

  20. Do two-level systems and boson peak persist or vanish in hyperaged geological glasses of amber?

    NASA Astrophysics Data System (ADS)

    Pérez-Castañeda, T.; Jiménez-Riobóo, R. J.; Ramos, M. A.

    2016-03-01

    In this work, we extend, review and jointly discuss earlier experiments conducted by us in hyperaged geological glasses, either in Dominican amber (20 million years old) or in Spanish amber from El Soplao (110 million years old). After characterization of their thermodynamic and elastic properties (using Differential Scanning Calorimetry around the glass-transition temperature, and measuring mass density and sound velocity), their specific heat was measured at low and very low temperatures. By directly comparing pristine amber samples (i.e. highly stabilized polymer glasses after ageing for millions of years) to the same samples after being totally or partially rejuvenated, we have found that the two most prominent universal "anomalous" low-temperature properties of glasses, namely the tunnelling two-level systems and the so-called "boson peak", persist essentially unchanged in both types of hyperaged geological glasses. Therefore, non-Debye low-energy excitations of glasses appear to be robust, intrinsic properties of non-crystalline solids which do not vanish by accessing to very deep states in the potential energy landscape.

  1. Molecular and Morphological Evidence Challenges the Records of the Extant Liverwort Ptilidium pulcherrimum in Eocene Baltic Amber

    PubMed Central

    Heinrichs, Jochen; Scheben, Armin; Lee, Gaik Ee; Váňa, Jiří; Schäfer-Verwimp, Alfons; Krings, Michael; Schmidt, Alexander R.

    2015-01-01

    Preservation of liverworts in amber, a fossilized tree resin, is often exquisite. Twenty-three fossil species of liverworts have been described to date from Eocene (35–50 Ma) Baltic amber. In addition, two inclusions have been assigned to the extant species Ptilidium pulcherrimum (Ptilidiales or Porellales). However, the presence of the boreal P. pulcherrimum in the subtropical or warm-temperate Baltic amber forest challenges the phytogeographical interpretation of the Eocene flora. A re-investigation of one of the fossils believed to be P. pulcherrimum reveals that this specimen in fact represents the first fossil evidence of the genus Tetralophozia, and thus is re-described here as Tetralophozia groehnii sp. nov. A second fossil initially assigned to P. pulcherrimum is apparently lost, and can be reassessed only based on the original description and illustrations. This fossil is morphologically similar to the extant North Pacific endemic Ptilidium californicum, rather than P. pulcherrimum. Divergence time estimates based on chloroplast DNA sequences provide evidence of a Miocene origin of P. pulcherrimum, and thus also argue against the presence of this taxon in the Eocene. Ptilidium californicum originated 25–43 Ma ago. As a result, we cannot rule out that the Eocene fossil belongs to P. californicum. Alternatively, the fossil might represent a stem lineage element of Ptilidium or an early crown group species with morphological similarities to P. californicum. PMID:26536603

  2. Molecular and Morphological Evidence Challenges the Records of the Extant Liverwort Ptilidium pulcherrimum in Eocene Baltic Amber.

    PubMed

    Heinrichs, Jochen; Scheben, Armin; Lee, Gaik Ee; Váňa, Jiří; Schäfer-Verwimp, Alfons; Krings, Michael; Schmidt, Alexander R

    2015-01-01

    Preservation of liverworts in amber, a fossilized tree resin, is often exquisite. Twenty-three fossil species of liverworts have been described to date from Eocene (35-50 Ma) Baltic amber. In addition, two inclusions have been assigned to the extant species Ptilidium pulcherrimum (Ptilidiales or Porellales). However, the presence of the boreal P. pulcherrimum in the subtropical or warm-temperate Baltic amber forest challenges the phytogeographical interpretation of the Eocene flora. A re-investigation of one of the fossils believed to be P. pulcherrimum reveals that this specimen in fact represents the first fossil evidence of the genus Tetralophozia, and thus is re-described here as Tetralophozia groehnii sp. nov. A second fossil initially assigned to P. pulcherrimum is apparently lost, and can be reassessed only based on the original description and illustrations. This fossil is morphologically similar to the extant North Pacific endemic Ptilidium californicum, rather than P. pulcherrimum. Divergence time estimates based on chloroplast DNA sequences provide evidence of a Miocene origin of P. pulcherrimum, and thus also argue against the presence of this taxon in the Eocene. Ptilidium californicum originated 25-43 Ma ago. As a result, we cannot rule out that the Eocene fossil belongs to P. californicum. Alternatively, the fossil might represent a stem lineage element of Ptilidium or an early crown group species with morphological similarities to P. californicum. PMID:26536603

  3. Monolithic InGaN-based white light-emitting diodes with blue, green, and amber emissions

    NASA Astrophysics Data System (ADS)

    Lee, Sung-Nam; Paek, H. S.; Kim, H.; Jang, T.; Park, Y.

    2008-02-01

    We demonstrated a monolithic white light-emitting diodes (LEDs) epitaxial structure with blue, green, and amber emissions by introducing the blue InGaN /GaN five quantum wells (QWs) and InGaN /GaN single quantum well (SQW) with In-phase separated green/amber emissions as an active layer. Three wavelength emissions were developed by increasing the thickness of InGaN SQW grown on blue InGaN five QWs. From high resolution transmission electron microscope, In-phase separation was clearly observed in a 3.5-nm-thick InGaN SQW. In-phase separation would be generated by the spinodal decomposition which was promoted by the composition pulling effect related to the increment of well thickness. Therefore, white lighting LEDs with three wavelengths for blue emission from InGaN /GaN five QWs and green/amber emissions were achieved by the In-phase separation in InGaN SQW.

  4. Demonstration of amber-green light emitting diodes with lattice-mismatched AlInP active region

    NASA Astrophysics Data System (ADS)

    Christian, Theresa; Beaton, Daniel; Mukherjee, Kunal; Alberi, Kirstin; Mascarenhas, Angelo; Fitzgerald, Eugene

    2013-03-01

    Future solid-state lamps based on all-LED white light emission will require four emitter colors (red, amber, green, and blue) to achieve good color rendering while maintaining high efficiency. Traditional LED material systems are well-suited to the red and blue ends of the spectrum but there is not yet a clear front-runner material for efficient light emission in the amber-green wavelength range (570 - 595 nm). The compound semiconductor alloy AlxIn1-xP has the potential to achieve this target due to its high direct bandgap. This talk will present results from our recent fabrication of amber-green LEDs featuring an AlInP double-heterostructure device structure. Cladding layers for carrier confinement are achieved through control of atomic ordering in the AlInP material. To fully exploit the high direct bandgap that occurs at lattice constants below that of GaAs, these devices are grown on InGaAs/GaAs virtual substrates. Devices are characterized in terms of current-voltage behavior, electroluminescence emission spectra and drive current dependence.

  5. Near-infrared interferometric observation of the Herbig Ae star HD 144432 with VLTI/AMBER

    NASA Astrophysics Data System (ADS)

    Chen, L.; Kreplin, A.; Wang, Y.; Weigelt, G.; Hofmann, K.-H.; Kraus, S.; Schertl, D.; Lagarde, S.; Natta, A.; Petrov, R.; Robbe-Dubois, S.; Tatulli, E.

    2012-05-01

    Aims: We study the sub-AU-scale circumstellar environment of the Herbig Ae star HD 144432 with near-infrared VLTI/AMBER observations to investigate the structure of its inner dust disk. Methods: The interferometric observations were carried out with the AMBER instrument in the H and K band. We interpret the measured H- and K-band visibilities, the near- and mid-infrared visibilities from the literature, and the spectral energy distribution (SED) of HD 144432 by using geometric ring models and ring-shaped temperature-gradient disk models with power-law temperature distributions. Results: We derive a K-band ring-fit radius of 0.17 ± 0.01 AU and an H-band radius of 0.18 ± 0.01 AU (for a distance of 145 pc). This measured K-band radius of ~0.17 AU lies in the range between the dust sublimation radius of ~0.13 AU (predicted for a dust sublimation temperature of 1500 K and gray dust) and the prediction of models including backwarming (~0.27 AU). We find that an additional extended halo component is required in both the geometric and temperature-gradient modeling. In the best-fit temperature-gradient model, the disk consists of two components. The inner part of the disk is a thin ring with an inner radius of ~0.21 AU, a temperature of ~1600 K, and a ring thickness ~0.02 AU. The outer part extends from ~1 AU to ~10 AU with an inner temperature of ~400 K. We find that the disk is nearly face-on with an inclination angle of <28°. Conclusions: Our temperature-gradient modeling suggests that the near-infrared excess is dominated by emission from a narrow, bright rim located at the dust sublimation radius, while an extended halo component contributes ~6% to the total flux at 2 μm. The mid-infrared model emission has a two-component structure with ~20% of the flux originating from the inner ring and the rest from the outer parts. This two-component structure is indicative of a disk gap, which is possibly caused by the shadow of a puffed-up inner rim. Based on observations

  6. Functional and Regulatory Biomolecular Networks Organized by DNA Nanostructures

    NASA Astrophysics Data System (ADS)

    Liu, Minghui

    DNA has recently emerged as an extremely promising material to organize molecules on nanoscale. The reliability of base recognition, self-assembling behavior, and attractive structural properties of DNA are of unparalleled value in systems of this size. DNA scaffolds have already been used to organize a variety of molecules including nanoparticles and proteins. New protein-DNA bio-conjugation chemistries make it possible to precisely position proteins and other biomolecules on underlying DNA scaffolds, generating multi-biomolecule pathways with the ability to modulate intermolecular interactions and the local environment. This dissertation focuses on studying the application of using DNA nanostructure to direct the self-assembly of other biomolecular networks to translate biochemical pathways to non-cellular environments. Presented here are a series of studies toward this application. First, a novel strategy utilized DNA origami as a scaffold to arrange spherical virus capsids into one-dimensional arrays with precise nanoscale positioning. This hierarchical self-assembly allows us to position the virus particles with unprecedented control and allows the future construction of integrated multi-component systems from biological scaffolds using the power of rationally engineered DNA nanostructures. Next, discrete glucose oxidase (GOx)/ horseradish peroxidase (HRP) enzyme pairs were organized on DNA origami tiles with controlled interenzyme spacing and position. This study revealed two different distance-dependent kinetic processes associated with the assembled enzyme pairs. Finally, a tweezer-like DNA nanodevice was designed and constructed to actuate the activity of an enzyme/cofactor pair. Using this approach, several cycles of externally controlled enzyme inhibition and activation were successfully demonstrated. This principle of responsive enzyme nanodevices may be used to regulate other types of enzymes and to introduce feedback or feed-forward control loops.

  7. Bridging Nano- and Microtribology in Mechanical and Biomolecular Layers

    NASA Astrophysics Data System (ADS)

    Tomala, Agnieszka; Göçerler, Hakan; Gebeshuber, Ille C.

    The physical and chemical composition of surfaces determine various important properties of solids such as corrosion rates, adhesive properties, frictional properties, catalytic activity, wettability, contact potential and - finally and most importantly - failure mechanisms. Very thin, weak layers (of man-made and biological origin) on much harder substrates that reduce friction are the focus of the micro- and nanotribological investigations presented in this chapter.Biomolecular layers fulfil various functions in organs of the human body. Examples comprise the skin that provides a protective physical barrier between the body and the environment, preventing unwanted inward and outward passage of water and electrolytes, reducing penetration by destructive chemicals, arresting the penetration of microorganisms and external antigens and absorbing radiation from the sun, or the epithelium of the cornea that blocks the passage of foreign material, such as dust, water and bacteria, into the eye and that contributes to the lubrication layer that ensures smooth movement of the eyelids over the eyeballs.Monomolecular thin films, additive-derived reaction layers and hard coatings are widely used to tailor tribological properties of surfaces. Nanotribological investigations on these substrates can reveal novel properties regarding the orientation of chemisorbed additive layers, development of rubbing films with time and the relation of frictional properties to surface characteristics in diamond coatings.Depending on the questions to be answered with the tribological research, various micro- and nanotribological measurement methods are applied, including scanning probe microscopy (AFM, FFM), scanning electron microscopy, microtribometer investigations, angle-resolved photoelectron spectroscopy and optical microscopy. Thoughts on the feasibility of a unified approach to energy-dissipating systems and how it might be reached (touching upon new ways of scientific publishing

  8. Soft Supercharging of Biomolecular Ions in Electrospray Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Chingin, Konstantin; Xu, Ning; Chen, Huanwen

    2014-06-01

    The charge states of biomolecular ions in ESI-MS can be significantly increased by the addition of low-vapor supercharging (SC) reagents into the spraying solution. Despite the considerable interest from the community, the mechanistic aspects of SC are not well understood and are hotly debated. Arguments that denaturation accounts for the increased charging observed in proteins sprayed from aqueous solutions containing SC reagent have been published widely, but often with incomplete or ambiguous supporting data. In this work, we explored ESI MS charging and SC behavior of several biopolymers including proteins and DNA oligonucleotides. Analytes were ionized from 100 mM ammonium acetate (NH4Ac) aqueous buffer in both positive (ESI+) and negative (ESI-) ion modes. SC was induced either with m-NBA or by the elevated temperature of ESI capillary. For all the analytes studied we, found striking differences in the ESI MS response to these two modes of activation. The data suggest that activation with m-NBA results in more extensive analyte charging with lower degree of denaturation. When working solution with m-NBA was analyzed at elevated temperatures, the SC effect from m-NBA was neutralized. Instead, the net SC effect was similar to the SC effect achieved by thermal activation only. Overall, our observations indicate that SC reagents enhance ESI charging of biomolecules via distinctly different mechanism compared with the traditional approaches based on analyte denaturation. Instead, the data support the hypothesis that the SC phenomenon involves a direct interaction between a biopolymer and SC reagent occurring in evaporating ESI droplets.

  9. 1-D Imaging of the Dynamical Atmosphere of the Red Supergiant Betelgeuse in the CO First Overtone Lines with VLTI/AMBER

    NASA Astrophysics Data System (ADS)

    Ohnaka, K.

    2014-09-01

    We present high-spatial and high-spectral resolution observations of the red supergiant Betelgeuse in the CO first overtone lines near 2.3μm with the AMBER instrument at the Very Large Telescope Interferometer (VLTI). Our AMBER observations in 2008 spatially resolved the gas motions in a stellar atmosphere (photosphere and extended molecular outer atmosphere) for the first time other than the Sun. From our second observations one year later, we have reconstructed 1-D images in the individual CO lines with an angular resolution of 9.8 mas and a spectral resolution of 6000 by applying the self-calibration technique to restore the Fourier phase from the differential phase measurements. The reconstructed 1-D images reveal that the star appears different in the blue and red wing of the individual CO lines. In the blue wing, the star shows a pronounced, asymmetrically extended component at least up to 1.3 R⋆, while such a component does not appear in the red wing 1-D image. This can be explained by a model in which the CO gas patch (or clump) more than half as large as the star is moving slightly outward with 0-5 km s-1, while the gas in the remaining region is infalling fast with 20-30 km s-1. Comparison between the CO line data taken in 2008 and 2009 shows a significant time variation in the dynamics of the photosphere and outer atmosphere. However, the 1-D images in the continuum show only a slight deviation from a limb-darkened disk with an angular diameter of 42.49±0.06 mas, which leads to an effective temperature of 3690± 54 K. Moreover, the continuum data taken in 2008 and 2009 reveal no or only marginal time variations, much smaller than the maximum variation predicted by the current 3-D convection simulation. The derived continuum diameter also shows that the near-IR size of Betelgeuse has been nearly constant over the last 18 years, in marked contrast to the recently reported noticeable decrease in the mid-IR size.

  10. An asymmetry detected in the disk of κ Canis Majoris with AMBER/VLTI

    NASA Astrophysics Data System (ADS)

    Meilland, A.; Millour, F.; Stee, P.; Domiciano de Souza, A.; Petrov, R. G.; Mourard, D.; Jankov, S.; Robbe-Dubois, S.; Spang, A.; Aristidi, E.; Antonelli, P.; Beckmann, U.; Bresson, Y.; Chelli, A.; Dugué, M.; Duvert, G.; Gennari, S.; Glück, L.; Kern, P.; Lagarde, S.; Le Coarer, E.; Lisi, F.; Malbet, F.; Perraut, K.; Puget, P.; Rantakyrö, F.; Roussel, A.; Tatulli, E.; Weigelt, G.; Zins, G.; Accardo, M.; Acke, B.; Agabi, K.; Altariba, E.; Arezki, B.; Baffa, C.; Behrend, J.; Blöcker, T.; Bonhomme, S.; Busoni, S.; Cassaing, F.; Clausse, J.-M.; Colin, J.; Connot, C.; Delboulbé, A.; Driebe, T.; Feautrier, P.; Ferruzzi, D.; Forveille, T.; Fossat, E.; Foy, R.; Fraix-Burnet, D.; Gallardo, A.; Giani, E.; Gil, C.; Glentzlin, A.; Heiden, M.; Heininger, M.; Hernandez Utrera, O.; Hofmann, K.-H.; Kamm, D.; Kiekebusch, M.; Kraus, S.; Le Contel, D.; Le Contel, J.-M.; Lesourd, T.; Lopez, B.; Lopez, M.; Magnard, Y.; Marconi, A.; Mars, G.; Martinot-Lagarde, G.; Mathias, P.; Mège, P.; Monin, J.-L.; Mouillet, D.; Nussbaum, E.; Ohnaka, K.; Pacheco, J.; Perrier, C.; Rabbia, Y.; Rebattu, S.; Reynaud, F.; Richichi, A.; Robini, A.; Sacchettini, M.; Schertl, D.; Schöller, M.; Solscheid, W.; Stefanini, P.; Tallon, M.; Tallon-Bosc, I.; Tasso, D.; Testi, L.; Vakili, F.; von der Lühe, O.; Valtier, J.-C.; Vannier, M.; Ventura, N.

    2007-03-01

    Aims:We study the geometry and kinematics of the circumstellar environment of the Be star κ CMa in the Brγ emission line and its nearby continuum. Methods: We use the AMBER/VLTI instrument operating in the K band, which provides a spatial resolution of about 6 mas with a spectral resolution of 1500, to study the kinematics within the disk and to infer its rotation law. To obtain more kinematical constraints we also use a high spectral resolution Paβ line profile obtain in December 2005 at the Observatorio do Pico do Dios, Brazil and we compile V/R line profile variations and spectral energy distribution data points from the literature. Results: Using differential visibilities and differential phases across the Brγ line we detect an asymmetry in the disk. Moreover, we found that κ CMa seems difficult to fit within the classical scenario for Be stars, illustrated recently by α Arae observations, i.e. a fast rotating B star close to its breakup velocity surrounded by a Keplerian circumstellar disk with an enhanced polar wind. We discuss the possibility that κ CMa is a critical rotator with a Keplerian rotating disk and examine whether if the detected asymmetry can be interpreted within the “one-armed” viscous disk framework. Based on observations collected at the European Southern Observatory, Paranal, Chile, within the guaranteed time programme 074.A-9025(A).

  11. Amber fossils demonstrate deep-time stability of Caribbean lizard communities.

    PubMed

    Sherratt, Emma; del Rosario Castañeda, María; Garwood, Russell J; Mahler, D Luke; Sanger, Thomas J; Herrel, Anthony; de Queiroz, Kevin; Losos, Jonathan B

    2015-08-11

    Whether the structure of ecological communities can exhibit stability over macroevolutionary timescales has long been debated. The similarity of independently evolved Anolis lizard communities on environmentally similar Greater Antillean islands supports the notion that community evolution is deterministic. However, a dearth of Caribbean Anolis fossils--only three have been described to date--has precluded direct investigation of the stability of anole communities through time. Here we report on an additional 17 fossil anoles in Dominican amber dating to 15-20 My before the present. Using data collected primarily by X-ray microcomputed tomography (X-ray micro-CT), we demonstrate that the main elements of Hispaniolan anole ecomorphological diversity were in place in the Miocene. Phylogenetic analysis yields results consistent with the hypothesis that the ecomorphs that evolved in the Miocene are members of the same ecomorph clades extant today. The primary axes of ecomorphological diversity in the Hispaniolan anole fauna appear to have changed little between the Miocene and the present, providing evidence for the stability of ecological communities over macroevolutionary timescales. PMID:26216976

  12. InGaN-based UV/blue/green/amber LEDs

    NASA Astrophysics Data System (ADS)

    Mukai, Takashi; Yamada, Motokazu; Nakamura, Shuji

    1999-04-01

    High-efficient light emitting diodes (LEDs) emitting red, amber, green, blue, and ultraviolet light have been obtained through the use of an InGaN active layers instead of GaN active layers. Red LEDs with an emission wavelength of 680 nm which emission energy was smaller than the band-gap energy of InN were fabricated mainly resulting from the piezoelectric field due to the strain. The localized energy states caused by In composition fluctuation in the InGaN active layer seem to be related to the high efficiency of the InGaN-based emitting devices in spite of having a large number of threading dislocations. InGaN single-quantum-well- structure blue LEDs were grown on epitaxially laterally overgrown GaN and sapphire substrates. The emission spectra showed the similar blue shift with increasing forward currents between both LEDs. The output power of both LEDs was almost the same, as high as 6 mW at a current of 20 mA. These results indicate that the In composition fluctuation is not caused by dislocations, the dislocations are not effective to reduce the efficiency of the emission, and that the dislocations from the leakage current pathway in InGaN.

  13. Amber fossils demonstrate deep-time stability of Caribbean lizard communities

    PubMed Central

    Sherratt, Emma; del Rosario Castañeda, María; Garwood, Russell J.; Mahler, D. Luke; Sanger, Thomas J.; Herrel, Anthony; de Queiroz, Kevin; Losos, Jonathan B.

    2015-01-01

    Whether the structure of ecological communities can exhibit stability over macroevolutionary timescales has long been debated. The similarity of independently evolved Anolis lizard communities on environmentally similar Greater Antillean islands supports the notion that community evolution is deterministic. However, a dearth of Caribbean Anolis fossils—only three have been described to date—has precluded direct investigation of the stability of anole communities through time. Here we report on an additional 17 fossil anoles in Dominican amber dating to 15–20 My before the present. Using data collected primarily by X-ray microcomputed tomography (X-ray micro-CT), we demonstrate that the main elements of Hispaniolan anole ecomorphological diversity were in place in the Miocene. Phylogenetic analysis yields results consistent with the hypothesis that the ecomorphs that evolved in the Miocene are members of the same ecomorph clades extant today. The primary axes of ecomorphological diversity in the Hispaniolan anole fauna appear to have changed little between the Miocene and the present, providing evidence for the stability of ecological communities over macroevolutionary timescales. PMID:26216976

  14. Determining the Structure of a Cytoplasmic Polyadenylation Element Binding Protein via AMBER9

    NASA Astrophysics Data System (ADS)

    Saunders, Alison

    2010-03-01

    The neurons of Aplysia californica contain cytoplasmic polyadenylation element binding protein (CPEB). CPEB shows prion-like properties when expressed in yeast cells. Because prions have misfolded and normally folded forms, prions can code in neurons like binary codes in computers, with ``present'' and ``not present'' signals available. CPEB thus provides a candidate protein for the molecular basis of memory. I attempt to determine CPEB's structure, by first threading the known protein sequence around a β-helical structure. Threading is preformed by hand, and by a program written to minimize the energy cost of building the structure. I then analyze the stability of the thread using the molecular dynamics program AMBER9. I also analyze a protein of only glutamine (PolyQ) in a β-helical structure to substantiate my use of a β-helix with the glutamine-rich CPEB. I found PolyQ to be stable in a left-handed β-helical structure with eighteen residues per turn. A candidate structure for CPEB was located with the same β-helical structure.

  15. Refinement of the Sugar-Phosphate Backbone Torsion Beta for AMBER Force Fields Improves the Description of Z- and B-DNA.

    PubMed

    Zgarbová, Marie; Šponer, Jiří; Otyepka, Michal; Cheatham, Thomas E; Galindo-Murillo, Rodrigo; Jurečka, Petr

    2015-12-01

    Z-DNA duplexes are a particularly complicated test case for current force fields. We performed a set of explicit solvent molecular dynamics (MD) simulations with various AMBER force field parametrizations including our recent refinements of the ε/ζ and glycosidic torsions. None of these force fields described the ZI/ZII and other backbone substates correctly, and all of them underpredicted the population of the important ZI substate. We show that this underprediction can be attributed to an inaccurate potential for the sugar-phosphate backbone torsion angle β. We suggest a refinement of this potential, β(OL1), which was derived using our recently introduced methodology that includes conformation-dependent solvation effects. The new potential significantly increases the stability of the dominant ZI backbone substate and improves the overall description of the Z-DNA backbone. It also has a positive (albeit small) impact on another important DNA form, the antiparallel guanine quadruplex (G-DNA), and improves the description of the canonical B-DNA backbone by increasing the population of BII backbone substates, providing a better agreement with experiment. We recommend using β(OL1) in combination with our previously introduced corrections, εζ(OL1) and χ(OL4), (the combination being named OL15) as a possible alternative to the current β torsion potential for more accurate modeling of nucleic acids. PMID:26588601

  16. The Nuclear Magnetic Resonance of CCCC RNA Reveals a Right-Handed Helix, and Revised Parameters for AMBER Force Field Torsions Improve Structural Predictions from Molecular Dynamics

    PubMed Central

    2013-01-01

    The sequence dependence of RNA energetics is important for predicting RNA structure. Hairpins with Cn loops are consistently less stable than hairpins with other loops, which suggests the structure of Cn regions could be unusual in the “unfolded” state. For example, previous nuclear magnetic resonance (NMR) evidence suggested that polycytidylic acid forms a left-handed helix. In this study, UV melting experiments show that the hairpin formed by r(5′GGACCCCCGUCC) is less stable than r(5′GGACUUUUGUCC). NMR spectra for single-stranded C4 oligonucleotide, mimicking the unfolded hairpin loop, are consistent with a right-handed A-form-like helix. Comparisons between NMR spectra and molecular dynamics (MD) simulations suggest that recent reparametrizations, parm99χ_YIL and parm99TOR, of the AMBER parm99 force field improve the agreement between structural features for C4 determined by NMR and predicted by MD. Evidently, the force field revisions to parm99 improve the modeling of RNA energetics and therefore structure. PMID:23286901

  17. Species-level determination of closely related araucarian resins using FTIR spectroscopy and its implications for the provenance of New Zealand amber

    PubMed Central

    Sadowski, Eva-Maria; Schmidt, Alexander R.

    2015-01-01

    Some higher plants, both angiosperms and gymnosperms, can produce resins and some of these resins can polymerize and fossilize to form ambers. Various physical and chemical techniques have been used to identify and profile different plant resins and have then been applied to fossilized resins (ambers), to try to detect their parent plant affinities and understand the process of polymerization, with varying levels of success. Here we focus on resins produced from today’s most resinous conifer family, the Araucariaceae, which are thought to be the parent plants of some of the Southern Hemisphere’s fossil resin deposits. Fourier transform infrared (FTIR) spectra of the resins of closely related Araucariaceae species were examined to test whether they could be distinguished at genus and species level and whether the results could then be used to infer the parent plant of a New Zealand amber. The resin FTIR spectra are distinguishable from each other, and the three Araucaria species sampled produced similar FTIR spectra, to which Wollemia resin is most similar. Interspecific variability of the FTIR spectra is greatest in the three Agathis species tested. The New Zealand amber sample is similar in key shared features with the resin samples, but it does differ from the extant resin samples in key distinguishing features, nonetheless it is most similar to the resin of Agathis australis in this dataset. However on comparison with previously published FTIR spectra of similar aged amber and older (Eocene) resinites both found in coals from New Zealand and fresh Agathis australis resin, our amber has some features that imply a relatively immature resin, which was not expected from an amber of the Miocene age. PMID:26157631

  18. Patient and carer experiences of clinical uncertainty and deterioration, in the face of limited reversibility: A comparative observational study of the AMBER care bundle

    PubMed Central

    Bristowe, Katherine; Carey, Irene; Hopper, Adrian; Shouls, Susanna; Prentice, Wendy; Caulkin, Ruth; Higginson, Irene J; Koffman, Jonathan

    2015-01-01

    Background: Clinical uncertainty is emotionally challenging for patients and carers and creates additional pressures for those clinicians in acute hospitals. The AMBER care bundle was designed to improve care for patients identified as clinically unstable, deteriorating, with limited reversibility and at risk of dying in the next 1–2 months. Aim: To examine the experience of care supported by the AMBER care bundle compared to standard care in the context of clinical uncertainty, deterioration and limited reversibility. Design: A comparative observational mixed-methods study using semi-structured qualitative interviews and a followback survey. Setting/participants: Three large London acute tertiary National Health Service hospitals. Nineteen interviews with 23 patients and carers (10 supported by AMBER care bundle and 9 standard care). Surveys completed by next of kin of 95 deceased patients (59 AMBER care bundle and 36 standard care). Results: The AMBER care bundle was associated with increased frequency of discussions about prognosis between clinicians and patients (χ2 = 4.09, p = 0.04), higher awareness of their prognosis by patients (χ2 = 4.29, p = 0.04) and lower clarity in the information received about their condition (χ2 = 6.26, p = 0.04). Although the consistency and quality of communication were not different between the two groups, those supported by the AMBER care bundle described more unresolved concerns about caring for someone at home. Conclusion: Awareness of prognosis appears to be higher among patients supported by the AMBER care bundle, but in this small study this was not translated into higher quality communication, and information was judged less easy to understand. Adequately powered comparative evaluation is urgently needed. PMID:25829443

  19. From Correlation to Causality: Statistical Approaches to Learning Regulatory Relationships in Large-Scale Biomolecular Investigations.

    PubMed

    Ness, Robert O; Sachs, Karen; Vitek, Olga

    2016-03-01

    Causal inference, the task of uncovering regulatory relationships between components of biomolecular pathways and networks, is a primary goal of many high-throughput investigations. Statistical associations between observed protein concentrations can suggest an enticing number of hypotheses regarding the underlying causal interactions, but when do such associations reflect the underlying causal biomolecular mechanisms? The goal of this perspective is to provide suggestions for causal inference in large-scale experiments, which utilize high-throughput technologies such as mass-spectrometry-based proteomics. We describe in nontechnical terms the pitfalls of inference in large data sets and suggest methods to overcome these pitfalls and reliably find regulatory associations. PMID:26731284

  20. g_contacts: Fast contact search in bio-molecular ensemble data

    NASA Astrophysics Data System (ADS)

    Blau, Christian; Grubmuller, Helmut

    2013-12-01

    Short-range interatomic interactions govern many bio-molecular processes. Therefore, identifying close interaction partners in ensemble data is an essential task in structural biology and computational biophysics. A contact search can be cast as a typical range search problem for which efficient algorithms have been developed. However, none of those has yet been adapted to the context of macromolecular ensembles, particularly in a molecular dynamics (MD) framework. Here a set-decomposition algorithm is implemented which detects all contacting atoms or residues in maximum O(Nlog(N)) run-time, in contrast to the O(N2) complexity of a brute-force approach. Catalogue identifier: AEQA_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEQA_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 8945 No. of bytes in distributed program, including test data, etc.: 981604 Distribution format: tar.gz Programming language: C99. Computer: PC. Operating system: Linux. RAM: ≈Size of input frame Classification: 3, 4.14. External routines: Gromacs 4.6[1] Nature of problem: Finding atoms or residues that are closer to one another than a given cut-off. Solution method: Excluding distant atoms from distance calculations by decomposing the given set of atoms into disjoint subsets. Running time:≤O(Nlog(N)) References: [1] S. Pronk, S. Pall, R. Schulz, P. Larsson, P. Bjelkmar, R. Apostolov, M. R. Shirts, J.C. Smith, P. M. Kasson, D. van der Spoel, B. Hess and Erik Lindahl, Gromacs 4.5: a high-throughput and highly parallel open source molecular simulation toolkit, Bioinformatics 29 (7) (2013).

  1. Exploring the Conformational Transitions of Biomolecular Systems Using a Simple Two-State Anisotropic Network Model

    PubMed Central

    Jo, Sunhwan; Bahar, Ivet; Roux, Benoît

    2014-01-01

    Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints. The two-state potential has a cusp hypersurface in the configuration space where the energies from both the ENMs are equal. We first search for the minimum energy structure on the cusp hypersurface and then treat it as the transition state. The continuous pathway is subsequently constructed by following the steepest descent energy minimization trajectories starting from the transition state on each side of the cusp hypersurface. Application to several systems of broad biological interest such as adenylate kinase, ATP-driven calcium pump SERCA, leucine transporter and glutamate transporter shows that ANMPathway yields results in good agreement with those from other similar methods and with data obtained from all-atom molecular dynamics simulations, in support of the utility of this simple and efficient approach. Notably the method provides experimentally testable predictions, including the formation of non-native contacts during the transition which we were able to detect in two of the systems we studied. An open-access web server has been created to deliver ANMPathway results

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

    SciTech Connect

    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 applications. Further

  3. Large-scale molecular dynamics simulation: Effect of polarization on thrombin-ligand binding energy.

    PubMed

    Duan, Li L; Feng, Guo Q; Zhang, Qing G

    2016-01-01

    Molecular dynamics (MD) simulations lasting 500 ns were performed in explicit water to investigate the effect of polarization on the binding of ligands to human α-thrombin based on the standard nonpolarizable AMBER force field and the quantum-derived polarized protein-specific charge (PPC). The PPC includes the electronic polarization effect of the thrombin-ligand complex, which is absent in the standard force field. A detailed analysis and comparison of the results of the MD simulation with experimental data provided strong evidence that intra-protein, protein-ligand hydrogen bonds and the root-mean-square deviation of backbone atoms were significantly stabilized through electronic polarization. Specifically, two critical hydrogen bonds between thrombin and the ligand were broken at approximately 190 ns when AMBER force field was used and the number of intra-protein backbone hydrogen bonds was higher under PPC than under AMBER. The thrombin-ligand binding energy was computed using the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) method, and the results were consistent with the experimental value obtained using PPC. Because hydrogen bonds were unstable, it was failed to predict the binding affinity under the AMBER force field. Furthermore, the results of the present study revealed that differences in the binding free energy between AMBER and PPC almost comes from the electrostatic interaction. Thus, this study provides evidence that protein polarization is critical to accurately describe protein-ligand binding. PMID:27507430

  4. Large-scale molecular dynamics simulation: Effect of polarization on thrombin-ligand binding energy

    PubMed Central

    Duan, Li L.; Feng, Guo Q.; Zhang, Qing G.

    2016-01-01

    Molecular dynamics (MD) simulations lasting 500 ns were performed in explicit water to investigate the effect of polarization on the binding of ligands to human α-thrombin based on the standard nonpolarizable AMBER force field and the quantum-derived polarized protein-specific charge (PPC). The PPC includes the electronic polarization effect of the thrombin-ligand complex, which is absent in the standard force field. A detailed analysis and comparison of the results of the MD simulation with experimental data provided strong evidence that intra-protein, protein-ligand hydrogen bonds and the root-mean-square deviation of backbone atoms were significantly stabilized through electronic polarization. Specifically, two critical hydrogen bonds between thrombin and the ligand were broken at approximately 190 ns when AMBER force field was used and the number of intra-protein backbone hydrogen bonds was higher under PPC than under AMBER. The thrombin-ligand binding energy was computed using the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) method, and the results were consistent with the experimental value obtained using PPC. Because hydrogen bonds were unstable, it was failed to predict the binding affinity under the AMBER force field. Furthermore, the results of the present study revealed that differences in the binding free energy between AMBER and PPC almost comes from the electrostatic interaction. Thus, this study provides evidence that protein polarization is critical to accurately describe protein-ligand binding. PMID:27507430

  5. Yeast Ca(2+)-signal transduction inhibitors isolated from Dominican amber prevent the degranulation of RBL-2H3 cells through the inhibition of Ca(2+)-influx.

    PubMed

    Abe, Tomomi; Kobayashi, Miki; Okawa, Yusuke; Inui, Tomoki; Yoshida, Jun; Higashio, Hironori; Shinden, Hisao; Uesugi, Shota; Koshino, Hiroyuki; Kimura, Ken-Ichi

    2016-09-01

    A new norlabdane compound, named kujigamberol has previously been isolated from Kuji amber (but not from Baltic amber) by activity guided fractionation. However, there has been no study of biological compounds in Dominican amber. Biological activities were examined using the hypersensitive mutant yeast (zds1Δ erg3Δ pdr1Δ pdr3Δ) with respect to Ca(2+)-signal transduction, enzymes and rat basophilic leukemia (RBL)-2H3 cells. The structures were elucidated on the basis of spectral analysis including high resolution (HR)-EI-MS, 1D NMR and 2D NMR. Three diterpenoid compounds, 5(10)-halimen-15-oic acid (1), 3-cleroden-15-oic acid (2) and 8-labden-15-oic acid (3), which are different from the bioactive compounds in Kuji and Baltic ambers, were isolated from Dominican amber. They inhibited both calcineurin (CN) (IC50=40.0, 21.2 and 34.2μM) and glycogen synthase kinase-3β (GSK-3β) (IC50=48.9, 43.8 and 41.1μM) which are involved in the growth restored activity against the mutant yeast. The most abundant compound 2 showed inhibitory activity against both degranulation and Ca(2+)-influx in RBL-2H3 cells. The compounds having the growth restoring activity against the mutant yeast have potential as anti-allergic compounds. PMID:27491756

  6. Force-Field Induced Bias in the Structure of Aβ21-30: A Comparison of OPLS, AMBER, CHARMM, and GROMOS Force Fields.

    PubMed

    Smith, Micholas Dean; Rao, J Srinivasa; Segelken, Elizabeth; Cruz, Luis

    2015-12-28

    In this work we examine the dynamics of an intrinsically disordered protein fragment of the amyloid β, the Aβ21-30, under seven commonly used molecular dynamics force fields (OPLS-AA, CHARMM27-CMAP, AMBER99, AMBER99SB, AMBER99SB-ILDN, AMBER03, and GROMOS53A6), and three water models (TIP3P, TIP4P, and SPC/E). We find that the tested force fields and water models have little effect on the measures of radii of gyration and solvent accessible surface area (SASA); however, secondary structure measures and intrapeptide hydrogen-bonding are significantly modified, with AMBER (99, 99SB, 99SB-ILDN, and 03) and CHARMM22/27 force-fields readily increasing helical content and the variety of intrapeptide hydrogen bonds. On the basis of a comparison between the population of helical and β structures found in experiments, our data suggest that force fields that suppress the formation of helical structure might be a better choice to model the Aβ21-30 peptide. PMID:26629886

  7. Afro-Asian cockroach from Chiapas amber and the lost Tertiary American entomofauna

    NASA Astrophysics Data System (ADS)

    Vršanský, Peter; Cifuentes-Ruiz, Paulina; Vidlička, Ľubomír; Čiampor, Fedor; Vega, Francisco J.

    2011-10-01

    Cockroach genera with synanthropic species (Blattella, Ectobius, Supella, Periplaneta, Diploptera and ?Blatta), as well as other insects such as honeybees, although natively limited to certain continents nowadays, had circumtropic distribution in the past. The ease of their reintroduction into their former range suggests a post-Early Miocene environmental stress which led to the extinction of cosmopolitan Tertiary entomofauna in the Americas, whilst in Eurasia, Africa and Australia this fauna survived. This phenomenon is demonstrated here on a low diversity (10 spp.) living cockroach genus Supella, which is peculiar for the circumtropical synanthropic brownbanded cockroach S. longipalpa and also for its exclusively free-living cavicolous species restricted to Africa. S. (Nemosupella) miocenica sp. nov. from the Miocene amber of Chiapas in Mexico is a sister species to the living S. mirabilis from the Lower Guinea forests and adjacent savannas. The difference is restricted to the shape of the central macula on the pronotum, and size, which may indicate the around-Miocene origin of the living, extremely polymorphic Supella species and possibly also the isochronic invasion into the Americas. The species also has a number of characteristics of the Asian (and possibly also Australian) uniform genus Allacta (falling within the generic variability of Supella) suggesting Supella is a direct ancestor of the former. The present species is the first significant evidence for incomplete hiati between well defined cockroach genera — a result of the extensive fossil record of the group. The reported specimen is covered by a mycelium of a parasitic fungus Cordyceps or Entomophthora.

  8. Immersion mode ice nucleation measurements with the new Portable Immersion Mode Cooling chAmber (PIMCA)

    NASA Astrophysics Data System (ADS)

    Kohn, Monika; Lohmann, Ulrike; Welti, André; Kanji, Zamin A.

    2016-05-01

    The new Portable Immersion Mode Cooling chAmber (PIMCA) has been developed for online immersion freezing of single-immersed aerosol particles. PIMCA is a vertical extension of the established Portable Ice Nucleation Chamber (PINC). PIMCA immerses aerosol particles into cloud droplets before they enter PINC. Immersion freezing experiments on cloud droplets with a radius of 5-7 μm at a prescribed supercooled temperature (T) and water saturation can be conducted, while other ice nucleation mechanisms (deposition, condensation, and contact mode) are excluded. Validation experiments on reference aerosol (kaolinite, ammonium sulfate, and ammonium nitrate) showed good agreement with theory and literature. The PIMCA-PINC setup was tested in the field during the Zurich AMBient Immersion freezing Study (ZAMBIS) in spring 2014 in Zurich, Switzerland. Significant concentrations of submicron ambient aerosol triggering immersion freezing at T > 236 K were rare. The mean frozen cloud droplet number concentration was estimated to be 7.22·105 L-1 for T < 238 K and determined from the measured frozen fraction and cloud condensation nuclei (CCN) concentrations predicted for the site at a typical supersaturation of SS = 0.3%. This value should be considered as an upper limit of cloud droplet freezing via immersion and homogeneous freezing processes. The predicted ice nucleating particle (INP) concentration based on measured total aerosol larger than 0.5 μm and the parameterization by DeMott et al. (2010) at T = 238 K is INPD10=54 ± 39 L-1. This is a lower limit as supermicron particles were not sampled with PIMCA-PINC during ZAMBIS.

  9. VLTI focal instrument AMBER: results of laboratory commissioning of the warm optics

    NASA Astrophysics Data System (ADS)

    Robbe-Dubois, Sylvie; Bresson, Yves; Antonelli, Pierre; Bonhomme, S.; Lagarde, Stephane; Martinot-Lagarde, Gregoire; Petrov, Romain G.; Puget, Pascal; Reynaud, Francois; Roussel, Andre; Rousselet-Perraut, Karine; Tassot, Daniel; Vannier, Martin

    2003-02-01

    AMBER, Astronomical Multi BEam combineR, is the near-infrared focal instrument dedicated to the VLTI. It is designed to combine three of the VLTI Telescopes and to work simultaneously in the J, H and K spectral bands (1.1 to 2.4 μm). The instrumental concept and its opto-mechanic specifications were defined in order to reach the ambitious scientific requirements to satisfy the core astrophysical programs. The project passed the Final Design Review in May 2001, phase which marks the acceptation of the instrument final design and the beginning of the construction and tests. After this phase, optics and mechanical systems have been receptioned since February 2002, for the laboratory tests and alignments. The cooled spectrograph and its cryostat is assembled at the Osservatorio di Arcetri in Firenze, Italy and the cooled detector at the Max-Planck-Institut für Radioastronomie in Bonn, Deutschland. The warm optics, including spatial filter in K and artificial sources injection system, have been pre-aligned at the Observatoire de la Côte d'Azur in Nice, France to validate most of the alignment procedure, the required element accuracies and the associated degrees of freedom. The whole instrument is then currently fully assembled and optimized at the Laboratoire d'Astrophysique de l'Observatoire de Grenoble, France. Its sensitivity and final performance will be evaluated in order to reach the Preliminary Acceptance in Europe, scheduled beginning 2003. This paper gives the results of the warm optics laboratory commissioning.

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

    ERIC Educational Resources Information Center

    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…

  11. A COMPUTATIONAL LIBRARY OF THE BIOMOLECULAR TARGETS FOR TOXICITY: RECEPTORS IN THE ENDOCRINE SYSTEM

    EPA Science Inventory

    A Computational Library of the Biomolecular Targets for Toxicity: Receptors in the Endocrine System

    Authors: James R. Rabinowitz and Stephen B. Little, MTB/ECD/NHEERL/ORD, and Huajun Fan, Curriculum in Toxicology, University of North Carolina
    Structure activity models ...

  12. Supporting Representational Competence in High School Biology with Computer-Based Biomolecular Visualizations

    ERIC Educational Resources Information Center

    Wilder, Anna; Brinkerhoff, Jonathan

    2007-01-01

    This study assessed the effectiveness of computer-based biomolecular visualization activities on the development of high school biology students' representational competence as a means of understanding and visualizing protein structure/function relationships. Also assessed were students' attitudes toward these activities. Sixty-nine students…

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

    ERIC Educational Resources Information Center

    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…

  14. A humidity-sensitive hydrogel-Bacillus spore composite for micropatterning of biomolecular gradients

    NASA Astrophysics Data System (ADS)

    Gieseck, Richard L.; Chan, Bin-Da; Savran, Cagri A.

    2013-08-01

    A composite material consisting of Bacillus subtilis spores suspended in a humidity sensitive hydrogel can be used to pattern biomolecules in different concentrations directly onto glass surfaces using a mechanical micromanipulator. By altering the relative humidity surrounding the composite gel during deposition, surface concentration of patterned biomolecules can be controlled and varied to create user-defined, biomolecular surface concentrations.

  15. A bacterial amber suppressor in Saccharomyces cerevisiae is selectively recognized by a bacterial aminoacyl-tRNA synthetase.

    PubMed Central

    Edwards, H; Schimmel, P

    1990-01-01

    Little is known about the conservation of determinants for the identities of tRNAs between organisms. We showed previously that Escherichia coli tyrosine tRNA synthetase can charge the Saccharomyces cerevisiae mitochondrial tyrosine tRNA in vivo, even though there are substantial sequence differences between the yeast mitochondrial and bacterial tRNAs. The S. cerevisiae cytoplasmic tyrosine tRNA differs in sequence from both its yeast mitochondrial and E. coli counterparts. To test whether the yeast cytoplasmic tyrosyl-tRNA synthetase recognizes the E. coli tRNA, we expressed various amounts of an E. coli tyrosine tRNA amber suppressor in S. cerevisiae. The bacterial tRNA did not suppress any of three yeast amber alleles, suggesting that the yeast enzymes retain high specificity in vivo for their homologous tRNAs. Moreover, the nucleotides in the sequence of the E. coli suppressor that are not shared with the yeast cytoplasmic tyrosine tRNA do not create determinants which are efficiently recognized by other yeast charging enzymes. Therefore, at least some of the determinants that influence in vivo recognition of the tyrosine tRNA are specific to the cell compartment and organism. In contrast, expression of the cognate bacterial tyrosyl-tRNA synthetase together with the bacterial suppressor tRNA led to suppression of all three amber alleles. The bacterial enzyme recognized its substrate in vivo, even when the amount of bacterial tRNA was less than about 0.05% of that of the total cytoplasmic tRNA. Images PMID:1690848

  16. A new fossil genus of net-winged beetles, with a brief review of amber Lycidae (Insecta: Coleoptera).

    PubMed

    Kazantsev, Sergey V

    2013-01-01

    A new fossil genus of net-winged beetles, Protolopheros gen. n., and a new species, Protolopheros hoffeinsorum sp. n., are described from the Baltic amber. The new taxon is placed in Erotini, next to Lopheros Leconte, 1881. The extant Pseudaplatopterus (Eropterus) Green, 1951, comb. n. is lowered in rank and placed as a subgenus of the fossil Pseudaplatopterus Kleine, 1940. The extant Kolibaceum (Laterialis) Kazantsev, 1990, comb. n. is lowered in rank and placed as a subgenus of the fossil Kolibaceum Winkler, 1987. PMID:24614452

  17. Two Flat-Backed Polydesmidan Millipedes from the Miocene Chiapas-Amber Lagerstätte, Mexico

    PubMed Central

    Riquelme, Francisco; Hernández-Patricio, Miguel; Martínez-Dávalos, Arnulfo; Rodríguez-Villafuerte, Mercedes; Montejo-Cruz, Maira; Alvarado-Ortega, Jesús; Ruvalcaba-Sil, José L.; Zúñiga-Mijangos, Luis

    2014-01-01

    Two species of fossil polydesmidan millipedes (Diplopoda: Polydesmida) embedded in amber are described from Miocene strata near Simojovel, in the Chiapas Highlands, Mexico. Maatidesmus paachtun gen. et sp. nov., placed into Chelodesmidae Cook, 1895, and Anbarrhacus adamantis gen. et sp. nov., assigned in the family Platyrhacidae Pocock, 1895. Morphological data from fossil specimens have been recovered using 3D X-ray micro-computed tomography and regular to infrared-reflected microscopy. Both fossil species are recognizable as new primarily but not exclusively, by collum margin modification and remarkable paranotal and metatergite dorsal sculpture. PMID:25162220

  18. Enhanced light output power of InGaN-based amber LEDs by strain-compensating AlN/AlGaN barriers

    NASA Astrophysics Data System (ADS)

    Iida, Daisuke; Lu, Shen; Hirahara, Sota; Niwa, Kazumasa; Kamiyama, Satoshi; Ohkawa, Kazuhiro

    2016-08-01

    We investigated the effect of a combined AlN/Al0.03Ga0.97N barrier on InGaN-based amber light-emitting diodes (LEDs) grown by metalorganic vapor-phase epitaxy. InGaN-based multiple quantum wells with a combined AlN/Al0.03Ga0.97N barrier showed intense photoluminescence with a narrow full-width at half-maximum. The amber LEDs with a combined AlN/Al0.03Ga0.97N barrier achieved a light output power enhanced approximately 2.5-fold at 20 mA compared to that of the LED with a combined AlN/GaN barrier, owing to the reduction of defects in InGaN active layers. Thus, the efficiency of high-In-content InGaN-based LEDs can be improved in the spectrum range of amber.

  19. Strong carrier localization effect in carrier dynamics of 585 nm InGaN amber light-emitting diodes

    SciTech Connect

    Li, Panpan; Li, Hongjian; Li, Zhi; Kang, Junjie; Yi, Xiaoyan; Li, Jinmin; Wang, Guohong

    2015-02-21

    Temperature dependence and time-resolved photoluminescence (TRPL) have been carried out to study carrier dynamics for 585 nm InGaN amber light-emitting diodes (LEDs). It is found that in InGaN amber LEDs, peak emission energy only shows a slight blueshift from 588 to 575 nm, as temperature increased from 10 K to 300 K. Moreover, radiative recombination lifetime has demonstrated independent of temperature based TRPL results. These two features indicate that a strong carrier localization effect plays a dominant role in carrier dynamics for InGaN amber LEDs. Also, activation energy of 40.3 meV is obtained through Arrhenius plot of PL intensity versus temperature.

  20. Hepatitis Delta Virus RNA Editing Is Highly Specific for the Amber/W Site and Is Suppressed by Hepatitis Delta Antigen

    PubMed Central

    Polson, Andrew G.; Ley, Herbert L.; Bass, Brenda L.; Casey, John L.

    1998-01-01

    RNA editing at adenosine 1012 (amber/W site) in the antigenomic RNA of hepatitis delta virus (HDV) allows two essential forms of the viral protein, hepatitis delta antigen (HDAg), to be synthesized from a single open reading frame. Editing at the amber/W site is thought to be catalyzed by one of the cellular enzymes known as adenosine deaminases that act on RNA (ADARs). In vitro, the enzymes ADAR1 and ADAR2 deaminate adenosines within many different sequences of base-paired RNA. Since promiscuous deamination could compromise the viability of HDV, we wondered if additional deamination events occurred within the highly base paired HDV RNA. By sequencing cDNAs derived from HDV RNA from transfected Huh-7 cells, we determined that the RNA was not extensively modified at other adenosines. Approximately 0.16 to 0.32 adenosines were modified per antigenome during 6 to 13 days posttransfection. Interestingly, all observed non-amber/W adenosine modifications, which occurred mostly at positions that are highly conserved among naturally occurring HDV isolates, were found in RNAs that were also modified at the amber/W site. Such coordinate modification likely limits potential deleterious effects of promiscuous editing. Neither viral replication nor HDAg was required for the highly specific editing observed in cells. However, HDAg was found to suppress editing at the amber/W site when expressed at levels similar to those found during HDV replication. These data suggest HDAg may regulate amber/W site editing during virus replication. PMID:9528763

  1. Characteristics of InGaN-Based UV/Blue/Green/Amber/Red Light-Emitting Diodes

    NASA Astrophysics Data System (ADS)

    Mukai, Takashi; Yamada, Motokazu; ShujiNakamura, ShujiNakamura

    1999-07-01

    Highly efficient light-emitting diodes (LEDs) emitting ultraviolet (UV), blue, green, amber and red light have been obtained through the use of InGaN active layers instead of GaN active layers. Red LEDs with an emission wavelength of 675 nm, whose emission energy was almost equal to the band-gap energy of InN, were fabricated. The dependence of the emission wavelength of the red LED on the current (blue shift) is dominated by both the band-filling effect of the localized energy states and the screening effect of the piezoelectric field. In the red LEDs, a phase separation of the InGaN layer was clearly observed in the emission spectra, in which blue and red emission peaks appeared. In terms of the temperature dependence of the LEDs, InGaN LEDs are superior to the conventional red and amber LEDs due to a large band offset between the active and cladding layers. The localized energy states caused by In composition fluctuation in the InGaN active layer contribute to the high efficiency of the InGaN-based emitting devices, in spite of the large number of threading dislocations and a large effect of the piezoelectric field. The blue and green InGaN-based LEDs had the highest external quantum efficiencies of 18% and 20% at low currents of 0.6 mA and 0.1 mA, respectively.

  2. PREFACE: India-Japan Workshop on Biomolecular Electronics & Organic Nanotechnology for Environment Preservation

    NASA Astrophysics Data System (ADS)

    Onoda, Mitsuyoshi; Malhotra, Bansi D.

    2012-04-01

    The 'India-Japan Workshop on Biomolecular Electronics & Organic Nanotechnology for Environment Preservation' (IJWBME 2011) will be held on 7-10 December 2011 at EGRET Himeji, Himeji, Hyogo, Japan. This workshop was held for the first time on 17-19 December 2009 at NPL, New Delhi. Keeping in mind the importance of organic nanotechnology and biomolecular electronics for environmental preservation and their anticipated impact on the economics of both the developing and the developed world, IJWBME 2009 was jointly organized by the Department of Biological Functions, Graduate School of Life Sciences and Systems Engineering, the Kyushu Institute of Technology (KIT), Kitakyushu, Japan, and the Department of Science & Technology Centre on Biomolecular Electronics (DSTCBE), National Physical Laboratory (NPL). Much progress in the field of biomolecular electronics and organic nanotechnology for environmental preservation is expected for the 21st Century. Organic optoelectronic devices, such as organic electroluminescent devices, organic thin-film transistors, organic sensors, biological systems and so on have especially attracted much attention. The main purpose of this workshop is to provide an opportunity for researchers interested in biomolecular electronics and organic nanotechnology for environmental preservation, to come together in an informal and friendly atmosphere and exchange technical knowledge and experience. We are sure that this workshop will be very useful and fruitful for all participants in summarizing the recent progress in biomolecular electronics and organic nanotechnology for environmental preservation and preparing new ground for the next generation. Many papers have been submitted from India and Japan and more than 30 papers have been accepted for presentation. The main topics of interest are as follows: Bioelectronics Biomolecular Electronics Fabrication Techniques Self-assembled Monolayers Nano-sensors Environmental Monitoring Organic Devices

  3. Specificity quantification of biomolecular recognition and its implication for drug discovery

    NASA Astrophysics Data System (ADS)

    Yan, Zhiqiang; Wang, Jin

    2012-03-01

    Highly efficient and specific biomolecular recognition requires both affinity and specificity. Previous quantitative descriptions of biomolecular recognition were mostly driven by improving the affinity prediction, but lack of quantification of specificity. We developed a novel method SPA (SPecificity and Affinity) based on our funneled energy landscape theory. The strategy is to simultaneously optimize the quantified specificity of the ``native'' protein-ligand complex discriminating against ``non-native'' binding modes and the affinity prediction. The benchmark testing of SPA shows the best performance against 16 other popular scoring functions in industry and academia on both prediction of binding affinity and ``native'' binding pose. For the target COX-2 of nonsteroidal anti-inflammatory drugs, SPA successfully discriminates the drugs from the diversity set, and the selective drugs from non-selective drugs. The remarkable performance demonstrates that SPA has significant potential applications in identifying lead compounds for drug discovery.

  4. Biomolecular implementation of a quasi sliding mode feedback controller based on DNA strand displacement reactions.

    PubMed

    Sawlekar, Rucha; Montefusco, Francesco; Kulkarni, Vishwesh; Bates, Declan G

    2015-08-01

    A fundamental aim of synthetic biology is to achieve the capability to design and implement robust embedded biomolecular feedback control circuits. An approach to realize this objective is to use abstract chemical reaction networks (CRNs) as a programming language for the design of complex circuits and networks. Here, we employ this approach to facilitate the implementation of a class of nonlinear feedback controllers based on sliding mode control theory. We show how a set of two-step irreversible reactions with ultrasensitive response dynamics can provide a biomolecular implementation of a nonlinear quasi sliding mode (QSM) controller. We implement our controller in closed-loop with a prototype of a biological pathway and demonstrate that the nonlinear QSM controller outperforms a traditional linear controller by facilitating faster tracking response dynamics without introducing overshoots in the transient response. PMID:26736420

  5. Blue, Green, and Amber InGaN/GaN Light-Emitting Diodes on Semipolar {11\\bar{2}2} GaN Bulk Substrates

    NASA Astrophysics Data System (ADS)

    Funato, Mitsuru; Ueda, Masaya; Kawakami, Yoichi; Narukawa, Yukio; Kosugi, Takao; Takahashi, Masayoshi; Mukai, Takashi

    2006-07-01

    We demonstrate the fabrication of blue, green, and amber InGaN/GaN light-emitting diodes (LEDs) on semipolar {11\\bar{2}2} bulk GaN substrates. The {11\\bar{2}2}GaN substrates used in this study are produced by cutting out from a c-oriented GaN bulk crystal grown by hydride vapor epitaxy. The LEDs have a dimension of 320 × 320 μm2 and are packed in an epoxide resin. The output power and external quantum efficiency (EQE) at a driving current of 20 mA are 1.76 mW and 3.0%, respectively, for the blue LED, 1.91 mW and 4.1% for the green LED, and 0.54 mW and 1.3% for the amber LED. The maximum output powers obtained with a maximum current of 200 mA are 19.0 mW (blue), 13.4 mW (green), and 1.9 mW (amber), while the maximum EQEs are 4.0% at 140 mA (blue), 4.9% at 0.2 mA (green), and 1.6% at 1 mA (amber). It is confirmed that the emission light is polarized along the [1\\bar{1}00] direction, reflecting the low crystal symmetry of the {11\\bar{2}2} plane.

  6. Exploiting the features of the finite state automata for biomolecular computing.

    PubMed

    Martínez-Pérez, Israel Marck; Ignatova, Zoya; Zimmermann, Karl-Heinz

    2009-01-01

    Here, we review patents that have emerged in the field of DNA-based computing focusing thereby on the discoveries using the concept of molecular finite state automata. A finite state automaton, operating on a finite sequence of symbols and converting information from one to another, provides a basis for developing molecular-scale autonomous programmable models of biomolecular computation at cellular level. We also provide a brief overview on inventions which methodologically support the DNA-based computational approach. PMID:19519583

  7. Testing Landscape Theory for Biomolecular Processes with Single Molecule Fluorescence Spectroscopy

    NASA Astrophysics Data System (ADS)

    Truex, Katherine; Chung, Hoi Sung; Louis, John M.; Eaton, William A.

    2015-07-01

    Although Kramers' theory for diffusive barrier crossing on a 1D free energy profile plays a central role in landscape theory for complex biomolecular processes, it has not yet been rigorously tested by experiment. Here we test this 1D diffusion scenario with single molecule fluorescence measurements of DNA hairpin folding. We find an upper bound of 2.5 μ s for the average transition path time, consistent with the predictions by theory with parameters determined from optical tweezer measurements.

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

    PubMed

    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. PMID:27187990

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

    PubMed

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

    2016-08-01

    Biomolecule-templated or biotemplated metal nanoclusters (NCs) are ultrasmall (<2 nm) metal (Au, Ag) particles stabilized by a certain type of 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. PMID:27377035

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

    PubMed Central

    2016-01-01

    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. PMID:27057643

  11. Application of isothermal titration calorimetry and column chromatography for identification of biomolecular targets.

    PubMed

    Zhou, Xingding; Kini, R Manjunatha; Sivaraman, J

    2011-02-01

    This protocol describes a method for identifying unknown target proteins from a mixture of biomolecules for a given drug or a lead compound. This method is based on a combination of chromatography and isothermal titration calorimetry (ITC) where ITC is used as a tracking tool. The first step involves the use of ITC to confirm the binding of ligand to a component in the biomolecular mixture. Subsequently, the biomolecular mixture is fractionated by chromatography, and the binding of the ligand with individual fractions (or subfractions) is verified by ITC. The iteration of chromatographic purification on the fractions combined with ITC results in identifying the target protein. This method is useful when the target protein or ligand is unknown and/or not amenable to labeling, chemical modification or immobilization. This protocol has been successfully used by our team and by others to identify both low-abundance and highly abundant target proteins present in biomolecular mixtures. With this protocol, it takes approximately 3-5 d to identify the target protein from a mixture. PMID:21293457

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

    PubMed

    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. PMID:27057643

  13. Small-Angle Scattering and Neutron Contrast Variation for Studying Bio-Molecular Complexes

    NASA Astrophysics Data System (ADS)

    Whitten, Andrew E.; Trewhella, Jill

    Structural molecular biology over the past several decades has progressed from studies of the individual proteins, subunits, and domains that accomplish specific biochemistry to seeking to understand the dynamic bio-molecular complexes and assemblies that are responsible for biological function. This progress has led to an expansion of the structural analysis “tool box” to include methods that complement the mainstay techniques of the field: X-ray crystallography, nuclear magnetic resonance (NMR), and cryo-electron microscopy. Small-angle scattering of X-rays or neutrons is one such complementary technique that provides information on the size and shape of scattering particles in solution. This low-resolution structural information can be a powerful complement to high-resolution structural data, especially for the study of bio-molecular interactions with ligands or each other. Further, exploitation of the different neutron-scattering properties of the stable isotopes of hydrogen (1H and 2H) can be used to enrich the information available from the small-angle scattering data, especially for bio-molecular complexes.

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

    PubMed Central

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

    2013-01-01

    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. PMID:24352481

  15. Modelling the interaction of several bisphosphonates with hydroxyapatite using the generalised AMBER force field

    NASA Astrophysics Data System (ADS)

    Robinson, Janine; Cukrowski, Ignacy; Marques, Helder M.

    2006-12-01

    The ability of the Generalised AMBER Force Field (GAFF) of Kollman and co-workers to model the structures of bisphosphonate ligands, C(R 1)(R 2)(PO 32-) 2, important compounds in the treatment of bone cancer, by molecular mechanics methods is evaluated. The structure of 50 bisphosphonates and nine bisphosphonate esters were predicted and compared to their crystal structures. Partial charges were assigned from a RHF/6-31G ∗ single point calculation at the geometry of the crystal structure. Additional parameters required for GAFF were determined using the methods of the force field's developers. The structures were found to be well replicated with virtually all bond lengths reproduced to within 0.015 Å, or within 1.2 σ of the crystallographic mean. Bond angles were reproduced to within 1.9° (0.8 σ). The observed gauche or anti conformation of the molecules was reproduced, although in several instances gauche conformations observed in the solid state energy-minimised into anti conformations, and vice versa. The interaction of MDP (R 1 = R 2 = H), HEDP (R 1 = OH, R 2 = CH 3), APD (R 1 = OH, R 2 = (CH 2) 2NH 3+), alendronate (R 1 = OH, R 2 = (CH 2) 3NH 3+) and neridronate (R 1 = OH, R 2 = (CH 2) 5NH 3+) with the (001), (010) and (100) faces of hydroxyapaptite was examined by energy-minimising 20 random orientations of each ligand 20 Å from the mineral (where there is no interaction), and then at about 8 Å from the surface whereupon the ligand relaxes onto the surface. The difference in energy between the two systems is the interaction energy. In all cases interaction with hydroxyapatite caused a decrease in energy. When modelled with a dielectric constant of 78 ɛo, non-bonded interactions dominate; electrostatic interactions become important when the dielectric constant is <10 ɛo. Irrespective of the value of the dielectric constant used, the structure of the ligands on the hydroxyapatite surface is very similar. On the (001) face, both phosphonate groups

  16. VLTI/AMBER observations of cold giant stars: atmospheric structures and fundamental parameters

    NASA Astrophysics Data System (ADS)

    Arroyo-Torres, B.; Martí-Vidal, I.; Marcaide, J. M.; Wittkowski, M.; Guirado, J. C.; Hauschildt, P. H.; Quirrenbach, A.; Fabregat, J.

    2014-06-01

    Aims: The main goal of this research is to determine the angular size and the atmospheric structures of cool giant stars (ɛ Oct, β Peg, NU Pav, ψ Peg, and γ Hya) and to compare them with hydrostatic stellar model atmospheres, to estimate the fundamental parameters, and to obtain a better understanding of the circumstellar environment. Methods: We conducted spectro-interferometric observations of ɛ Oct, β Peg, NU Pav, and ψ Peg in the near-infrared K band (2.13-2.47 μm), and γ Hya (1.9-2.47 μm) with the VLTI/AMBER instrument at medium spectral resolution (~1500). To obtain the fundamental parameters, we compared our data with hydrostatic atmosphere models (PHOENIX). Results: We estimated the Rosseland angular diameters of ɛ Oct, β Peg, NU Pav, ψ Peg, and γ Hya to be 11.66±1.50 mas, 16.87±1.00 mas, 13.03±1.75 mas, 6.31±0.35 mas, and 3.78±0.65 mas, respectively. Together with distances and bolometric fluxes (obtained from the literature), we estimated radii, effective temperatures, and luminosities of our targets. In the β Peg visibility, we observed a molecular layer of CO with a size similar to that modeled with PHOENIX. However, there is an additional slope in absorption starting around 2.3 μm. This slope is possibly due to a shell of H2O that is not modeled with PHOENIX (the size of the layer increases to about 5% with respect to the near-continuum level). The visibility of ψ Peg shows a low increase in the CO bands, compatible with the modeling of the PHOENIX model. The visibility data of ɛ Oct, NU Pav, and γ Hya show no increase in molecular bands. Conclusions: The spectra and visibilities predicted by the PHOENIX atmospheres agree with the spectra and the visibilities observed in our stars (except for β Peg). This indicates that the opacity of the molecular bands is adequately included in the model, and the atmospheres of our targets have an extension similar to the modeled atmospheres. The atmosphere of β Peg is more extended than

  17. Proton Solvation and Transport in Aqueous and Biomolecular Systems

    PubMed Central

    Swanson, Jessica M. J.; Maupin, C. Mark; Chen, Hanning; Petersen, Matt K.; Xu, Jiancong; Wu, Yujie; Voth, Gregory A.

    2008-01-01

    The excess proton in aqueous media plays a pivotal role in many fundamental chemical (e.g., acid-base chemistry) and biological (e.g., bioenergetics and enzyme catalysis) processes. Understanding the hydrated proton is, therefore, crucial for chemistry, biology, and materials sciences. Although well studied for over 200 years, excess proton solvation and transport remains to this day mysterious, surprising, and perhaps even misunderstood. In this feature article various efforts to address this problem through computer modeling and simulation will be described. Applications of computer simulations to a number of important and interesting systems will be presented, highlighting the roles of charge delocalization and Grotthuss shuttling, a phenomenon unique in many ways to the excess proton in water. PMID:17429993

  18. On the systematic position of Baltimartyria Skalski, 1995 and description of a new species from Baltic amber (Lepidoptera, Micropterigidae)

    PubMed Central

    Mey, Wolfram

    2011-01-01

    Abstract This paper describes a rare case of a male moth in Baltic amber in an excellent position for establishing a species. The moth represents the second species of the genus Baltimartyria Skalski, 1995, described herein as Baltimartyria rasnitsyni sp. n. The detection of this new species prompts research on the systematic position of the genus within the family Micropterigidae. The genus was found to provide none of the apomorphic characters that would allow placement in one of the monophyletic lineages within the family. The genus is provisionally assigned to the “southern sabatincoid group”, a weakly supported assemblage of Southern Hemisphere genera. The sister genus has still to be determined. Baltimartyria is the first North Hemisphere representative in this group. Some general aspects of historical biogeography relevant for the group are briefly discussed. PMID:22259287

  19. Development of green, yellow, and amber light emitting diodes using InGaN multiple quantum well structures

    NASA Astrophysics Data System (ADS)

    Barletta, Philip T.; Acar Berkman, E.; Moody, Baxter F.; El-Masry, Nadia A.; Emara, Ahmed M.; Reed, Mason J.; Bedair, S. M.

    2007-04-01

    The authors present optical and electrical data for long wavelength (573-601nm) InGaN /GaN multiple quantum well light emitting diodes (LEDs) grown by metal organic chemical vapor deposition. These results are achieved by optimizing the active layer growth temperature and the quantum well width. Also, the p-GaN is grown at low temperature to avoid the disintegration of the InGaN quantum wells with high InN content. A redshift is observed for both the green and yellow LEDs upon decreasing the injection current at low current regime. In the case of the yellow LED, this shift is enough to push emission into the amber (601nm ).

  20. Amber-green light-emitting diodes using order-disorder AlxIn1-xP heterostructures

    NASA Astrophysics Data System (ADS)

    Christian, Theresa M.; Beaton, Daniel A.; Mukherjee, Kunal; Alberi, Kirstin; Fitzgerald, Eugene A.; Mascarenhas, Angelo

    2013-08-01

    We demonstrate amber-green emission from AlxIn1-xP light-emitting diodes (LEDs) with luminescence peaked at 566 nm and 600 nm. The LEDs are metamorphically grown on GaAs substrates via a graded InyGa1-yAs buffer layer and feature electron confinement based on the control of AlxIn1-xP CuPt atomic ordering. A control sample fabricated without order-disorder carrier confinement is used to illustrate device improvement up to a factor of 3 in light output due to confinement at drive currents of 40 A/cm2. The light output at room temperature from our AlxIn1-xP LED structure emitting at 600 nm is 39% as bright as a GaxIn1-xP LED emitting at 650 nm.

  1. Internal quantum efficiency in yellow-amber light emitting AlGaN-InGaN-GaN heterostructures

    SciTech Connect

    Ngo, Thi Huong; Gil, Bernard; Valvin, Pierre; Damilano, Benjamin; Lekhal, Kaddour; De Mierry, Philippe

    2015-09-21

    We determine the internal quantum efficiency of strain-balanced AlGaN-InGaN-GaN hetero-structures designed for yellow-amber light emission, by using a recent model based on the kinetics of the photoluminescence decay initiated by Iwata et al. [J. Appl. Phys. 117, 075701 (2015)]. Our results indicate that low temperature internal quantum efficiencies sit in the 50% range and we measure that adding an AlGaN layer increases the internal quantum efficiency from 50% up to 57% with respect to the GaN-InGaN case. More dramatic, it almost doubles from 2.5% up to 4.3% at room temperature.

  2. Biomolecular electrostatics—I want your solvation (model)

    NASA Astrophysics Data System (ADS)

    Bardhan, Jaydeep P.

    2012-01-01

    We review the mathematical and computational foundations for implicit-solvent models in theoretical chemistry and molecular biophysics. These models are valuable theoretical tools for studying the influence of a solvent, often water or an aqueous electrolyte, on a molecular solute such as a protein. Detailed chemical and physical aspects of implicit-solvent models have been addressed in numerous exhaustive reviews, as have numerical algorithms for simulating the most popular models. This work highlights several important conceptual developments, focusing on selected works that spotlight the need for research at the intersections between chemical, biological, mathematical, and computational physics. To introduce the field to computational scientists, we begin by describing the basic theoretical ideas of implicit-solvent models and numerical implementations. We then address practical and philosophical challenges in parameterization, and major advances that speed up calculations (covering continuum theories based on Poisson as well as faster approximate theories such as generalized Born). We briefly describe the main shortcomings of existing models, and survey promising developments that deliver improved realism in a computationally tractable way, i.e. without increasing simulation time significantly. The review concludes with a discussion of ongoing modeling challenges and relevant trends in high-performance computing and computational science. See [1].

  3. Theoretical description of biomolecular hydration - Application to A-DNA

    SciTech Connect

    Garcia, A.E.; Hummer, G.; Soumpasis, D.M.

    1994-12-31

    The local density of water molecules around a biomolecule is constructed from calculated two- and three-points correlation functions of polar solvents in water using a Potential-of-Mean-Force (PMF) expansion. As a simple approximation, the hydration of all polar (including charged) groups in a biomolecule is represented by the hydration of water oxygen in bulk water, and the effect of non-polar groups on hydration are neglected, except for excluded volume effects. Pair and triplet correlation functions are calculated by molecular dynamics simulations. We present calculations of the structural hydration for ideal A-DNA molecules with sequences [d(CG){sub 5}]{sub 2} and [d(C{sub 5}G{sub 5})]{sub 2}. We find that this method can accurately reproduce the hydration patterns of A-DNA observed in neutron diffraction experiments on oriented DNA fibers.

  4. Electrostatics interactions in classical simulations.

    PubMed

    Cisneros, G Andrés; Babin, Volodymyr; Sagui, Celeste

    2013-01-01

    Electrostatic interactions are crucial for both the accuracy and performance of atomistic biomolecular simulations. In this chapter we review well-established methods and current developments aiming at efficiency and accuracy. Specifically, we review the classical Ewald summations, particle-particle particle-method particle-method Ewald algorithms, multigrid, fast multipole, and local methods. We also highlight some recent developments targeting more accurate, yet classical, representation of the molecular charge distribution. PMID:23034752

  5. Optimizing Fine-grained Communication in a Biomolecular Simulation Application on Cray XK6

    SciTech Connect

    Sun, Yanhua; Zheng, Gengbin; Mei, Chao; Phillips, James C.; Kale, Laxmikant V; Jones, Terry R

    2012-01-01

    Achieving good scaling for fine-grained communication intensive applications on modern supercomputers remains challenging. In our previous work, we have shown that such an application NAMD scales well on the full Jaguar XT5 without long-range interactions; Yet, with them, the speedup falters beyond 64K cores. Although the new Gemini interconnect on Cray XK6 has improved network performance, the challenges remain, and are likely to remain for other such networks as well. We analyze communication bottlenecks in NAMD and its CHARM++ runtime, using the Projections performance analysis tool. Based on the analysis, we optimize the runtime, built on the uGNI library for Gemini. We present several techniques to improve the fine-grained communication. Consequently, the performance of running 92224-atom Apoa1 with GPUs on TitanDev is improved by 36%. For 100-million-atom STMV, we improve upon the prior Jaguar XT5 result of 26 ms/step to 13 ms/step using 298,992 cores on Jaguar XK6.

  6. Biomolecular conjugation inside synthetic polymer nanopores viaglycoprotein-lectin interactions

    NASA Astrophysics Data System (ADS)

    Ali, Mubarak; Ramirez, Patricio; Tahir, Muhammad Nawaz; Mafe, Salvador; Siwy, Zuzanna; Neumann, Reinhard; Tremel, Wolfgang; Ensinger, Wolfgang

    2011-04-01

    We demonstrate the supramolecular bioconjugation of concanavalin A (Con A) protein with glycoenzymehorseradish peroxidase (HRP) inside single nanopores, fabricated in heavy ion tracked polymermembranes. Firstly, the HRP-enzyme was covalently immobilized on the inner wall of the pores using carbodiimide coupling chemistry. The immobilized HRP-enzyme molecules bear sugar (mannose) groups available for the binding of Con A protein. Secondly, the bioconjugation of Con A on the pore wall was achieved through its biospecific interactions with the mannose residues of the HRP enzyme. The immobilization of biomolecules inside the nanopore leads to the reduction of the available area for ionic transport, and this blocking effect can be exploited to tune the conductance and selectivity of the nanopore in aqueous solution. Both cylindrical and conical nanopores were used in the experiments. The possibility of obtaining two or more conductance states (output), dictated by the degree of nanopore blocking resulted from the different biomolecules in solution (input), as well as the current rectification properties obtained with the conical nanopore, could also allow implementing information processing at the nanometre scale. Model simulations based on the transport equations further verify the feasibility of the sensing procedure that involves concepts from supramolecular chemistry, molecular imprinting, recognition, and nanotechnology.

  7. Raman spectroscopy detects biomolecular changes associated with nanoencapsulated hesperetin treatment in experimental oral carcinogenesis

    NASA Astrophysics Data System (ADS)

    Gurushankar, K.; Gohulkumar, M.; Kumar, Piyush; Krishna, C. Murali; Krishnakumar, N.

    2016-03-01

    Recently it has been shown that Raman spectroscopy possesses great potential in the investigation of biomolecular changes of tumor tissues with therapeutic drug response in a non-invasive and label-free manner. The present study is designed to investigate the antitumor effect of hespertin-loaded nanoparticles (HETNPs) relative to the efficacy of native hesperetin (HET) in modifying the biomolecular changes during 7,12-dimethyl benz(a)anthracene (DMBA)-induced oral carcinogenesis using a Raman spectroscopic technique. Significant differences in the intensity and shape of the Raman spectra between the control and the experimental tissues at 1800-500 cm-1 were observed. Tumor tissues are characterized by an increase in the relative amount of proteins, nucleic acids, tryptophan and phenylalanine and a decrease in the percentage of lipids when compared to the control tissues. Further, oral administration of HET and its nanoparticulates restored the status of the lipids and significantly decreased the levels of protein and nucleic acid content. Treatment with HETNPs showed a more potent antitumor effect than treatment with native HET, which resulted in an overall reduction in the intensity of several biochemical Raman bands in DMBA-induced oral carcinogenesis being observed. Principal component and linear discriminant analysis (PC-LDA), together with leave-one-out cross validation (LOOCV) on Raman spectra yielded diagnostic sensitivities of 100%, 80%, 91.6% and 65% and specificities of 100%, 65%, 60% and 55% for classification of control versus DMBA, DMBA versus DMBA  +  HET, DMBA versus DMBA  +  HETNPs and DMBA  +  HET versus DMBA  +  HETNPs treated tissue groups, respectively. These results further demonstrate that Raman spectroscopy associated with multivariate statistical algorithms could be a valuable tool for developing a comprehensive understanding of the process of biomolecular changes, and could reveal the signatures of the

  8. Dynamic Expression of DNA Complexation with Self-assembled Biomolecular Clusters.

    PubMed

    Bartolami, Eline; Bessin, Yannick; Gervais, Virginie; Dumy, Pascal; Ulrich, Sébastien

    2015-08-24

    We report herein the implementation of a dynamic covalent chemistry approach to the generation of multivalent clusters for DNA recognition. We show that biomolecular clusters can be expressed in situ by a programmed self-assembly process using chemoselective ligations. The cationic clusters are shown, by fluorescence displacement assay, gel electrophoresis and isothermal titration calorimetry, to effectively complex DNA through multivalent interactions. The reversibility of the ligation was exploited to demonstrate that template effects occur, whereby DNA imposes component selection in order to favor the most active DNA-binding clusters. Furthermore, we show that a chemical effector can be used to trigger DNA release through component exchange reactions. PMID:26177835

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

    NASA Astrophysics Data System (ADS)

    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.

  10. Biomolecular interactions in HCV nucleocapsid-like particles as revealed by vibrational spectroscopy

    NASA Astrophysics Data System (ADS)

    Rodríguez-Casado, Arantxa; Molina, Marina; Carmona, Pedro

    2007-05-01

    Hepatitis C virus (HCV) occurs in the form of 55-65 nm spherical particles, but the structure of the virion remains to be clarified. Structural studies of HCV have been hampered by the lack of an appropriate cell culture system. However, structural analyses of HCV components can provide an essential framework for understanding of the molecular mechanism of virion assembly. This article reviews the potential of vibrational spectroscopy aimed at the knowledge of HCV structural biology, particularly regarding biomolecular interactions in nucleocapsid-like particles obtained in vitro.

  11. Two decades of studying non-covalent biomolecular assemblies by means of electrospray ionization mass spectrometry

    PubMed Central

    Hilton, Gillian R.; Benesch, Justin L. P.

    2012-01-01

    Mass spectrometry (MS) is a recognized approach for characterizing proteins and the complexes they assemble into. This application of a long-established physico-chemical tool to the frontiers of structural biology has stemmed from experiments performed in the early 1990s. While initial studies focused on the elucidation of stoichiometry by means of simple mass determination, developments in MS technology and methodology now allow researchers to address questions of shape, inter-subunit connectivity and protein dynamics. Here, we chart the remarkable rise of MS and its application to biomolecular complexes over the last two decades. PMID:22319100

  12. Polarization at metal–biomolecular interfaces in solution

    PubMed Central

    Heinz, Hendrik; Jha, Kshitij C.; Luettmer-Strathmann, Jutta; Farmer, Barry L.; Naik, Rajesh R.

    2011-01-01

    Metal surfaces in contact with water, surfactants and biopolymers experience attractive polarization owing to induced charges. This fundamental physical interaction complements stronger epitaxial and covalent surface interactions and remains difficult to measure experimentally. We present a first step to quantify polarization on even gold (Au) surfaces in contact with water and with aqueous solutions of peptides of different charge state (A3 and Flg-Na3) by molecular dynamics simulation in all-atomic resolution and a posteriori computation of the image potential. Attractive polarization scales with the magnitude of atomic charges and with the length of multi-poles in the aqueous phase such as the distance between cationic and anionic groups. The polarization energy per surface area is similar on aqueous Au {1 1 1} and Au {1 0 0} interfaces of approximately −50 mJ m−2 and decreases to −70 mJ m−2 in the presence of charged peptides. In molecular terms, the polarization energy corresponds to −2.3 and −0.1 kJ mol−1 for water in the first and second molecular layers on the metal surface, and to between −40 and 0 kJ mol−1 for individual amino acids in the peptides depending on the charge state, multi-pole length and proximity to the surface. The net contribution of polarization to peptide adsorption on the metal surface is determined by the balance between polarization by the peptide and loss of polarization by replaced surface-bound water. On metal surfaces with significant epitaxial attraction of peptides such as Au {1 1 1}, polarization contributes only 10–20% to total adsorption related to similar polarity of water and of amino acids. On metal surfaces with weak epitaxial attraction of peptides such as Au {1 0 0}, polarization is a major contribution to adsorption, especially for charged peptides (−80 kJ mol−1 for peptide Flg-Na3). A remaining water interlayer between the metal surface and the peptide then reduces losses in polarization energy

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

    NASA Astrophysics Data System (ADS)

    Fei, Yiyan; Landry, James P.; Li, Yanhong; Yu, Hai; Lau, Kam; Huang, Shengshu; Chokhawala, Harshal A.; Chen, Xi; Zhu, X. D.

    2013-11-01

    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.

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

    SciTech Connect

    Fei, Yiyan; Landry, James P.; Zhu, X. D.; Li, Yanhong; Yu, Hai; Lau, Kam; Huang, Shengshu; Chokhawala, Harshal A.; Chen, Xi

    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.

  15. A genomewide survey of bHLH transcription factors in the coral Acropora digitifera identifies three novel orthologous families, pearl, amber, and peridot.

    PubMed

    Gyoja, Fuki; Kawashima, Takeshi; Satoh, Nori

    2012-04-01

    Decoding the genome of the coral, Acropora digitifera, enabled us to characterize a nearly full set of 70 basic helix-loop-helix (bHLH) transcription factors in this organism. This number is comparable to 68 bHLH genes in the sea anemone, Nematostella vectensis, and larger than those in most other invertebrate metazoans. The 70 bHLH genes were assigned to 29 orthologous families previously reported. In addition, we identified three novel HLH orthologous families, which we designated pearl, amber, and peridot, increasing the number of orthologous families to 32. Pearl and amber orthologues were found in genomes and expressed sequenced tags (ESTs) of Mollusca and Annelida in addition to Cnidaria. Peridot orthologues were found in genomes and ESTs of Cephalochordata and Hemichordata in addition to Cnidaria. These three genes were likely lost in the clades of Drosophila melanogaster, Caenorhabditis elegans, and Homo sapiens during animal evolution. PMID:22419240

  16. Highly improved reliability of amber light emitting diode with Ca -α-SiAlON phosphor in glass formed by gas pressure sintering for automotive applications.

    PubMed

    Yoon, Chang-Bun; Kim, Sanghyun; Choi, Sung-Woo; Yoon, Chulsoo; Ahn, Sang Hyeon; Chung, Woon Jin

    2016-04-01

    Phosphor in glass (PiG) with 40 wt% of Ca-α-SiAlON phosphor and 60 wt% of Pb-free silicate glass was synthesized and mounted on a high-power blue LED to make an amber LED for automotive applications. Gas pressure sintering was applied after the conventional sintering process was used to achieve fully dense PiG plates. Changes in photoluminescence spectra and color coordination were inspected by varying the thickness of the plates that were mounted after optical polishing and machining. A trade-off between luminous flux and color purity was observed. The commercial feasibility of amber PiG packaged LED, which can satisfy international regulations for automotive components, was successfully demonstrated by examining the practical reliability under 85% humidity at an 85°C condition. PMID:27192294

  17. Rational optimization of amber suppressor tRNAs toward efficient incorporation of a non-natural amino acid into protein in a eukaryotic wheat germ extract.

    PubMed

    Ogawa, Atsushi; Namba, Yuki; Gakumasawa, Mai

    2016-03-01

    Amber suppression is a useful method of genetically incorporating a non-natural amino acid (NAA) into a protein during translation by utilizing an NAA-charged amber suppressor tRNA (sup-tRNA). A wheat germ extract (WGE) is suitable for this method by virtue of its high productivity and versatility in addition to its advantages as a cell-free translation system. However, in spite of this high potential, a genetic NAA incorporation system in WGE has not been sufficiently optimized in terms of sup-tRNAs, in contrast to that in E. coli and its cell extracts. We herein rationally optimized amber sup-tRNAs to efficiently incorporate a model NAA, p-acetyl-phenylalanine (AcPhe), into a protein in WGE, via flexizyme-based aminoacylation. The optimized sup-tRNA (named tLys-opt) that was pre-charged with AcPhe exclusively yielded up to 220 μg mL(-1) of AcPhe-incorporated protein (yellow fluorescent protein, YPet) under the optimal conditions. This high productivity is comparable to the best reported yield of a similar NAA-incorporated protein synthesized with an engineered aminoacyl-tRNA synthetase/sup-tRNA pair in WGE, despite the fact that tLys-opt that has released AcPhe was not reused at all in this study. The results clearly show both the necessity of optimizing sup-tRNAs for efficient NAA incorporation and the validity of our strategy for their optimization. Because the optimization strategy described here is expected to be applicable not only to amber sup-tRNAs for other NAAs but also to ones used in other acylation methods, it would facilitate the synthesis of large amounts of various types of NAA-incorporated proteins in WGE. PMID:26832824

  18. AMBER/VLTI observations of η Carinae with high spatial resolution and spectral resolutions of λ/Δ λ = 1500 and 12 000

    NASA Astrophysics Data System (ADS)

    Weigelt, G.; Driebe, T.; Hofmann, K.-H.; Kraus, S.; Petrov, R.; Schertl, D.

    2007-10-01

    We present the first NIR interferometric observations of the LBV η Carinae with high spectral resolution [Weigelt et al., 2007. Near-infrared interferometry of η Carinae with spectral resolutions of 1500 and 12000 using AMBER/VLTI. A&A 464, 87.]. Our observations demonstrate the potential of AMBER/VLTI to unveil new structures on the scales of milliarcseconds. The aim of this work is to study the wavelength dependence of η Car's optically thick wind region with a high spatial resolution of 5 mas (11 AU) and high spectral resolution. The observations were carried out with three 8.2 m VLTI Unit Telescopes. The raw data are interferograms obtained with spectral resolutions of λ/Δ λ = 1500 (MR-K mode) and 12 000 (HR-K mode). The observations were performed in the wavelength range around both the HeI 2.059 μm and the Brγ 2.166 μm emission lines. The spectrally dispersed AMBER interferograms allow us to investigate the wavelength dependence of the visibility, differential phase, and closure phase of η Car. If we fit [Hillier, D.J., Davidson, K., Ishibashi, K., Gull, T., 2001. On the Nature of the Central Source in η Carinae. ApJ 553, 837] model visibilities (Hillier et al., 2001) to the observed AMBER visibilities, we obtain 50% encircled-energy diameters of 4.3, 6.5, and 9.6 mas in the 2.17 μm continuum, the HeI, and the Brγ emission lines, respectively. We find good agreement between the measured visibilities and the predictions of the radiative transfer model of Hillier et al. (2001). Our observations support theoretical models of anisotropic winds from fast-rotating, luminous hot stars with enhanced high-velocity mass loss near the polar regions.

  19. A defensive behavior and plant-insect interaction in Early Cretaceous amber--The case of the immature lacewing Hallucinochrysa diogenesi.

    PubMed

    Pérez-de la Fuente, Ricardo; Delclòs, Xavier; Peñalver, Enrique; Engel, Michael S

    2016-03-01

    Amber holds special paleobiological significance due to its ability to preserve direct evidence of biotic interactions and animal behaviors for millions of years. Here we review the finding of Hallucinochrysa diogenesi Pérez-de la Fuente, Delclòs, Peñalver and Engel, 2012, a morphologically atypical larva related to modern green lacewings (Insecta: Neuroptera) that was described in Early Cretaceous amber from the El Soplao outcrop (northern Spain). The fossil larva is preserved with a dense cloud of fern trichomes that corresponds to the trash packet the insect gathered and carried on its back for camouflaging and shielding, similar to that which is done by its extant relatives. This finding supports the prominent role of wildfires in the paleoecosystem and provides direct evidence of both an ancient plant-insect interaction and an early acquisition of a defensive behavior in an insect lineage. Overall, the fossil of H. diogenesi showcases the potential that the amber record offers to reconstruct not only the morphology of fossil arthropods but, more remarkably, their lifestyles and ecological relationships. PMID:26319268

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

    PubMed

    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. PMID:25285850

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

    PubMed

    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. PMID:26410586

  2. Optimizing water hyperpolarization and dissolution for sensitivity-enhanced 2D biomolecular NMR

    NASA Astrophysics Data System (ADS)

    Olsen, Greg; Markhasin, Evgeny; Szekely, Or; Bretschneider, Christian; Frydman, Lucio

    2016-03-01

    A recent study explored the use of hyperpolarized water, to enhance the sensitivity of nuclei in biomolecules thanks to rapid proton exchanges with labile amide backbone and sidechain groups. Further optimizations of this approach have now allowed us to achieve proton polarizations approaching 25% in the water transferred into the NMR spectrometer, effective water T1 times approaching 40 s, and a reduction in the dilution demanded for the cryogenic dissolution process. Further hardware developments have allowed us to perform these experiments, repeatedly and reliably, in 5 mm NMR tubes. All these ingredients - particularly the ⩾3000× 1H polarization enhancements over 11.7 T thermal counterparts, long T1 times and a compatibility with high-resolution biomolecular NMR setups - augur well for hyperpolarized 2D NMR studies of peptides, unfolded proteins and intrinsically disordered systems undergoing fast exchanges of their protons with the solvent. This hypothesis is here explored by detailing the provisions that lead to these significant improvements over previous reports, and demonstrating 1D coherence transfer experiments and 2D biomolecular HMQC acquisitions delivering NMR spectral enhancements of 100-500× over their optimized, thermally-polarized, counterparts.

  3. Optimizing water hyperpolarization and dissolution for sensitivity-enhanced 2D biomolecular NMR.

    PubMed

    Olsen, Greg; Markhasin, Evgeny; Szekely, Or; Bretschneider, Christian; Frydman, Lucio

    2016-03-01

    A recent study explored the use of hyperpolarized water, to enhance the sensitivity of nuclei in biomolecules thanks to rapid proton exchanges with labile amide backbone and sidechain groups. Further optimizations of this approach have now allowed us to achieve proton polarizations approaching 25% in the water transferred into the NMR spectrometer, effective water T1 times approaching 40s, and a reduction in the dilution demanded for the cryogenic dissolution process. Further hardware developments have allowed us to perform these experiments, repeatedly and reliably, in 5mm NMR tubes. All these ingredients--particularly the ⩾ 3000× (1)H polarization enhancements over 11.7T thermal counterparts, long T1 times and a compatibility with high-resolution biomolecular NMR setups - augur well for hyperpolarized 2D NMR studies of peptides, unfolded proteins and intrinsically disordered systems undergoing fast exchanges of their protons with the solvent. This hypothesis is here explored by detailing the provisions that lead to these significant improvements over previous reports, and demonstrating 1D coherence transfer experiments and 2D biomolecular HMQC acquisitions delivering NMR spectral enhancements of 100-500× over their optimized, thermally-polarized, counterparts. PMID:26920830

  4. Extracting intrinsic dynamic parameters of biomolecular folding from single-molecule force spectroscopy experiments.

    PubMed

    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. PMID:26088347

  5. The generation of biomolecular patterns in highly porous collagen-GAG scaffolds using direct photolithography

    PubMed Central

    Martin, Teresa A.; Caliari, Steven R.; Williford, Paul D.; Harley, Brendan A.; Bailey, Ryan C.

    2014-01-01

    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. PMID:21397322

  6. A Microchip for Quantitative Analysis of CNS Axon Growth under Localized Biomolecular Treatments

    PubMed Central

    Park, Jaewon; Kim, Sunja; Park, Su Inn; Choe, Yoonsuck; Li, Jianrong; Han, Arum

    2013-01-01

    Growth capability of neurons is an essential factor in axon regeneration. To better understand how microenvironments influence axon growth, methods that allow spatial control of cellular microenvironments and easy quantification of axon growth are critically needed. Here, we present a microchip capable of physically guiding the growth directions of axons while providing physical and fluidic isolation from neuronal somata/dendrites that enables localized biomolecular treatments and linear axon growth. The microchip allows axons to grow in straight lines inside the axon compartments even after the isolation; therefore, significantly facilitating the axon length quantification process. We further developed an image processing algorithm that automatically quantifies axon growth. The effect of localized extracellular matrix components and brain-derived neurotropic factor treatments on axon growth was investigated. Results show that biomolecules may have substantially different effects on axon growth depending on where they act. For example, while chondroitin sulfate proteoglycan causes axon retraction when added to the axons, it promotes axon growth when applied to the somata. The newly developed microchip overcomes limitations of conventional axon growth research methods that lack localized control of biomolecular environments and are often performed at a significantly lower cell density for only a short period of time due to difficulty in monitoring of axonal growth. This microchip may serve as a powerful tool for investigating factors that promote axon growth and regeneration. PMID:24161788

  7. Photochemical grafting and patterning of biomolecular layers onto TiO2 thin films.

    PubMed

    Li, Bo; Franking, Ryan; Landis, Elizabeth C; Kim, Heesuk; Hamers, Robert J

    2009-05-01

    TiO2 thin films are highly stable and can be deposited onto a wide variety of substrate materials under moderate conditions. We demonstrate that organic alkenes will graft to the surface of TiO2 when illuminated with UV light at 254 nm and that the resulting layers provide a starting point for the preparation of DNA-modified TiO2 thin films exhibiting excellent stability and biomolecular selectivity. By using alkenes with a protected amino group at the distal end, the grafted layers can be deprotected to yield molecular layers with exposed primary amino groups that can then be used to covalently link DNA oligonucleotides to the TiO2 surface. We demonstrate that the resulting DNA-modified surfaces exhibit excellent selectivity toward complementary versus noncomplementary target sequences in solution and that the surfaces can withstand 25 cycles of hybridization and denaturation in 8.3 M urea with little or no degradation. Furthermore, the use of simple masking methods provides a way to directly control the spatial location of the grafted layers, thereby providing a way to photopattern the spatial distribution of biologically active molecules to the TiO2 surfaces. Using Ti films ranging from 10 to 100 nm in thickness allows the preparation of TiO2 films that range from highly reflective to almost completely transparent; in both cases, the photochemical grafting of alkenes can be used as a starting point for stable surfaces with good biomolecular recognition properties. PMID:20355886

  8. Characterization of a nanoscale S-layer protein based template for biomolecular patterning.

    PubMed

    Wong, Wing Sze; Yung, Pun To

    2014-01-01

    Well organized template for biomolecular conjugation is the foundation for biosensing. Most of the current devices are fabricated using lithographic patterning processes and self-assembly monolayer (SAM) methods. However, the research toward developing a sub-10 nm patterned, self-regenerated template on various types of substrates is limited, mainly due to the limited functional groups of the building material. Bacterial surface layer proteins (S-layer proteins) can self-assemble into ordered lattice with regular pore sizes of 2-8 nm on different material supports and interfaces. The ordered structure can regenerate after extreme variations of solvent conditions. In this work, we developed a nanoscale biomolecular template based on S-layer proteins on gold surface for fabrication of sensing layer in biosensors. S-layer proteins were isolated from Bacillus cereus, Lysinibacillus sphaericus and Geobacillus stearothermophilus. Protein concentrations were measured by Bradford assay. The protein purities were verified by SDS-PAGE, showing molecular weights ranging from 97-135 kDa. The hydrophilicity of the substrate surface was measured after surface treatments of protein recrystallization. Atomic force microscopic (AFM) measurement was performed on substrate surface, indicating a successful immobilization of a monolayer of S-layer protein with 8-9 nm height on gold surface. The template can be applied on various material supports and acts as a self-regenerated sensing layer of biosensors in the future. PMID:25570568

  9. Technology Development of Miniaturized Far-Infrared Sources for Biomolecular Spectroscopy

    NASA Technical Reports Server (NTRS)

    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.

  10. The close environment of high-mass X-ray binaries at high angular resolution. I. VLTI/AMBER and VLTI/PIONIER near-infrared interferometric observations of Vela X-1

    NASA Astrophysics Data System (ADS)

    Choquet, É.; Kervella, P.; Le Bouquin, J.-B.; Mérand, A.; Berger, J.-P.; Haubois, X.; Perrin, G.; Petrucci, P.-O.; Lazareff, B.; Pott, J.-U.

    2014-01-01

    Context. Recent improvements in the sensitivity and spectral resolution of X-ray observations have led to a better understanding of the properties of matter in the near vicinity of high-mass X-ray binaries (HMXB) hosting a supergiant star and a compact object. However, the geometry and physical properties of their environments on larger scales (up to a few stellar radii) are currently only predicted by simulations but have never been directly observed. Aims: We aim to explore the environment of Vela X-1 at a few stellar radii (R⋆) of the supergiant using spatially resolved observations in the near-infrared, and to study its dynamical evolution along the nine-day orbital period of the system. Methods: We observed Vela X-1 in 2010 and 2012 using near-infrared long baseline interferometry at the Very Large Telescope Interferometer (VLTI), respectively with the AMBER instrument in the K band (medium spectral resolution), and the PIONIER instrument in the H band (low spectral resolution). The PIONIER observations span one orbital period to monitor possible evolutions in the geometry of the system. Results: We resolved a structure of 8 ± 3 R⋆ from the AMBER K-band observations, and 2.0-1.2+0.7R* from the PIONIER H-band data. From the closure phase observable, we found that the circumstellar environment of Vela X-1 is symmetrical in the near-infrared. We observed comparable interferometric measurements between the continuum and the spectral lines in the K band, meaning that both emissions originate from the same forming region. From the monitoring of the system over one period in the H band in 2012, we found the signal to be constant with the orbital phase within the error bars. Conclusions: We propose three possible scenarios for this discrepancy between the two measurements: 1) there is a strong temperature gradient in the supergiant wind, leading to a hot component that is much more compact than the cool part of the wind observed in the K band; 2) we observed a

  11. Maternally inherited architecture in tertiary leaf beetles: paleoichnology of cryptocephaline fecal cases in Dominican and Baltic amber

    NASA Astrophysics Data System (ADS)

    Chaboo, Caroline S.; Engel, Michael S.; Chamorro-Lacayo, Maria Lourdes

    2009-09-01

    Complex ethological adaptations and intraspecific interactions leave few fossil traces. We document three Dominican (20 million years old [myo]) and Baltic (45 myo) amber fossils that exhibit firm evidence of highly integrated interactions between mothers and offspring in the diverse camptosomate lineage of beetles (Chrysomelidae, leaf beetles). As in contemporary species, these hard cases were initially constructed by mothers, then inherited and retained by offspring, which then elaborate this protective domicile with an unusual but economical building material, their feces. The three fossils are classified in the Subfamily Cryptocephalinae; two are classified in the tribe Chlamisini based on morphological evidence—the flattened head lacking a sharp keel and long legs with simple recurved untoothed claws. These diagnostic features are not clearly visible in the third specimen to permit more refined identification. These fossils provide more precise paleontological dating of tribal nodes within the cryptocephaline radiation of leaf beetles. These fossils are the first and earliest evidence of mother-offspring interaction, building behavior, and fecal recycling in Camptosomata beetles and of inheritance of architectural structures in beetles.

  12. Kinetics of tRNA(Pyl) -mediated amber suppression in Escherichia coli translation reveals unexpected limiting steps and competing reactions.

    PubMed

    Wang, Jinfan; Kwiatkowski, Marek; Forster, Anthony C

    2016-07-01

    The utility of ribosomal incorporation of unnatural amino acids (AAs) in vivo is generally restricted by low efficiencies, even with the most widely used suppressor tRNA(Pyl) . Because of the difficulties of studying incorporation in vivo, almost nothing is known about the limiting steps after tRNA charging. Here, we measured the kinetics of all subsequent steps using a purified Escherichia coli translation system. Dipeptide formation from initiator fMet-tRNA(fMet) and tRNA(Pyl) charged with allylglycine or methylserine displayed unexpectedly sluggish biphasic kinetics, ∼30-fold slower than for native substrates. The amplitude of the fast phases increased with increasing EF-Tu concentration, allowing measurement of Kd values of EF-Tu binding, both of which were ∼25-fold weaker than normal. However, binding could be increased ∼30-fold by lowering temperature. The fast phase rates were limited by the surprisingly ∼10-fold less efficient binding of EF-Tu:GTP:AA-tRNA(Pyl) ternary complex to the ribosomes, not GTP hydrolysis or peptide bond formation. Furthermore, processivity was unexpectedly impaired as ∼40% of the dipeptidyl-tRNA(Pyl) could not be elongated to tripeptide. Dipeptide formation was slow enough that termination due to misreading the UAG codon by non-cognate RF2 became very significant. This new understanding provides a framework for improving unnatural AA incorporation by amber suppression. Biotechnol. Bioeng. 2016;113: 1552-1559. © 2015 Wiley Periodicals, Inc. PMID:26705134

  13. Bridging the gap between chewing and sucking in the hemipteroid insects:
    new insights from Cretaceous amber.

    PubMed

    Yoshizawa, Kazunori; Lienhard, Charles

    2016-01-01

    The diversity of feeding apparatuses in insects far exceeds that observed in any other animal group. Consequently, tracking mouthpart innovation in insects is one of the keys toward understanding their diversification. In hemipteroid insects (clade Paraneoptera or Acercaria: lice, thrips, aphids, cicadas, bugs, etc.), the transition from chewing to piercing-and-sucking mouthparts is widely regarded as the turning point that enabled hyperdiversification of the Hemiptera, the fifth largest insect order. However, the transitional process from chewing to piercing-and-sucking in the Paraneoptera was hitherto completely unknown. In this paper, we report a well preserved mid Cretaceous amber fossil of the paraneopteran insect family Archipsyllidae and describe it as Mydiognathus eviohlhoffae gen. et sp. n. This species has elongate mandibles and styliform laciniae similar to Hemiptera but retains functional chewing mouthparts. A number of morphological characters place the Archipsyllidae as the sister group of the thrips plus hemipterans, which strongly suggests that the mouthparts of M. eviohlhoffae represent a transitional condition from primitive chewing to derived piercing-and-sucking mouthparts. The clade composed of Archipsyllidae, thrips, and hemipterans is here named Pancondylognatha, a new supra-ordinal taxon. Based on newly obtained information, we also assess the monophyly of the Paraneoptera, which was called into question by recent phylogenomic analyses. A phylogenetic analysis that includes Mydiognathus strongly supports the monophyly of the Paraneoptera. PMID:27396002

  14. Electrochemical sensor for multiplex screening of genetically modified DNA: identification of biotech crops by logic-based biomolecular analysis.

    PubMed

    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. PMID:23893064

  15. Investigation of the Human Disease Osteogenesis Imperfecta: A Research-Based Introduction to Concepts and Skills in Biomolecular Analysis

    ERIC Educational Resources Information Center

    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…

  16. Towards Simulations of Outer Membrane Proteins in Lipopolysaccharide Membranes

    SciTech Connect

    Soares, Thereza A.; Straatsma, TP

    2007-12-26

    Biomolecular simulation derived properties of LPS membranes that impact the structural and internal dynamics of transmembrane proteins are shown to exhibit good agreement with available experimental data within the time scale simulated, chosen force field and simulation conditions. The molecular model used offers an accurate representation of the LPS layer, including the high asymmetry and low fluidity characteristics of outer membranes. This contribution describes the data intensive analysis of the large molecular time trajectories generated for these systems using massively parallel computing resources.

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

    NASA Astrophysics Data System (ADS)

    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 (<15%). With this degree of control, existing protein crystal applications such as drug delivery and analytical sensors can reach their full potential. Applications for larger crystals with inherently ubiquitous pore structures could extend to materials used for 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

  18. Molecular dynamics simulations data of the twenty encoded amino acids in different force fields.

    PubMed

    Vitalini, F; Noé, F; Keller, B G

    2016-06-01

    We present extensive all-atom Molecular Dynamics (MD) simulation data of the twenty encoded amino acids in explicit water, simulated with different force fields. The termini of the amino acids have been capped to ensure that the dynamics of the Φ and ψ torsion angles are analogues to the dynamics within a peptide chain. We use representatives of each of the four major force field families: AMBER ff-99SBILDN [1], AMBER ff-03 [2], OPLS-AA/L [3], CHARMM27 [4] and GROMOS43a1 [5], [6]. Our data represents a library and test bed for method development for MD simulations and for force fields development. Part of the data set has been previously used for comparison of the dynamic properties of force fields (Vitalini et al., 2015) [7] and for the construction of peptide basis functions for the variational approach to molecular kinetics [8]. PMID:27054161

  19. Molecular dynamics simulations data of the twenty encoded amino acids in different force fields

    PubMed Central

    Vitalini, F.; Noé, F.; Keller, B.G.

    2016-01-01

    We present extensive all-atom Molecular Dynamics (MD) simulation data of the twenty encoded amino acids in explicit water, simulated with different force fields. The termini of the amino acids have been capped to ensure that the dynamics of the Φ and ψ torsion angles are analogues to the dynamics within a peptide chain. We use representatives of each of the four major force field families: AMBER ff-99SBILDN [1], AMBER ff-03 [2], OPLS-AA/L [3], CHARMM27 [4] and GROMOS43a1 [5], [6]. Our data represents a library and test bed for method development for MD simulations and for force fields development. Part of the data set has been previously used for comparison of the dynamic properties of force fields (Vitalini et al., 2015) [7] and for the construction of peptide basis functions for the variational approach to molecular kinetics [8]. PMID:27054161

  20. Piezoelectric tuning fork biosensors for the quantitative measurement of biomolecular interactions

    NASA Astrophysics Data System (ADS)

    Gonzalez, Laura; Rodrigues, Mafalda; Benito, Angel Maria; Pérez-García, Lluïsa; Puig-Vidal, Manel; Otero, Jorge

    2015-12-01

    The quantitative measurement of biomolecular interactions is of great interest in molecular biology. Atomic force microscopy (AFM) has proved its capacity to act as a biosensor and determine the affinity between biomolecules of interest. Nevertheless, the detection scheme presents certain limitations when it comes to developing a compact biosensor. Recently, piezoelectric quartz tuning forks (QTFs) have been used as laser-free detection sensors for AFM. However, only a few studies along these lines have considered soft biological samples, and even fewer constitute quantified molecular recognition experiments. Here, we demonstrate the capacity of QTF probes to perform specific interaction measurements between biotin-streptavidin complexes in buffer solution. We propose in this paper a variant of dynamic force spectroscopy based on representing adhesion energies E (aJ) against pulling rates v (nm s-1). Our results are compared with conventional AFM measurements and show the great potential of these sensors in molecular interaction studies.

  1. Biomolecular Self-Defense and Futility of High-Specificity Therapeutic Targeting

    PubMed Central

    Rosenfeld, Simon

    2011-01-01

    Robustness has been long recognized to be a distinctive property of living entities. While a reasonably wide consensus has been achieved regarding the conceptual meaning of robustness, the biomolecular mechanisms underlying this systemic property are still open to many unresolved questions. The goal of this paper is to provide an overview of existing approaches to characterization of robustness in mathematically sound terms. The concept of robustness is discussed in various contexts including network vulnerability, nonlinear dynamic stability, and self-organization. The second goal is to discuss the implications of biological robustness for individual-target therapeutics and possible strategies for outsmarting drug resistance arising from it. Special attention is paid to the concept of swarm intelligence, a well studied mechanism of self-organization in natural, societal and artificial systems. It is hypothesized that swarm intelligence is the key to understanding the emergent property of chemoresistance. PMID:22272063

  2. AFMPB: An adaptive fast multipole Poisson Boltzmann solver for calculating electrostatics in biomolecular systems

    SciTech Connect

    Lu, Benzhuo; Cheng, Xiaolin; Huang, Jingfang; McCammon, Jonathan

    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://mccammon.ucsd.edu/. This paper is a brief summary of the program: the algorithms, the implementation and the usage.

  3. A program to calculate non-bonded interaction energy in biomolecular aggregates.

    PubMed

    Sundaram, K; Prasad, C V

    1982-02-01

    This paper describes a program to calculate intermolecular as well as intramolecular electronic potential energy resulting from non-bonded interactions. The underlying theory is obtained by the application of Rayleigh-Schroedinger perturbation theory to non-overlap regions of a molecular system. The rigorous theoretical expressions for the energy terms are simplified by approximations consistent with those commonly employed in semi-empirical molecular orbital theories. The program is particularly suited for the study of biomolecular assemblies, and in situations where insight into contributions to total energy from various component interaction types is desired. The inclusion of the non-additive dispersion effects in this approach makes it especially interesting for the study of cooperative phenomena in the light of a recent finding [1]. PMID:7067416

  4. Biomolecular papain thin films grown by matrix assisted and conventional pulsed laser deposition: A comparative study

    NASA Astrophysics Data System (ADS)

    György, E.; Pérez del Pino, A.; Sauthier, G.; Figueras, A.

    2009-12-01

    Biomolecular papain thin films were grown both by matrix assisted pulsed laser evaporation (MAPLE) and conventional pulsed laser deposition (PLD) techniques with the aid of an UV KrF∗ (λ =248 nm, τFWHM≅20 ns) excimer laser source. For the MAPLE experiments the targets submitted to laser radiation consisted on frozen composites obtained by dissolving the biomaterial powder in distilled water at 10 wt % concentration. Conventional pressed biomaterial powder targets were used in the PLD experiments. The surface morphology of the obtained thin films was studied by atomic force microscopy and their structure and composition were investigated by Fourier transform infrared spectroscopy. The possible physical mechanisms implied in the ablation processes of the two techniques, under comparable experimental conditions were identified. The results showed that the growth mode, surface morphology as well as structure of the deposited biomaterial thin films are determined both by the incident laser fluence value as well as target preparation procedure.

  5. Quantitative assessment of electrostatic embedding in Density Functional Theory calculations of biomolecular systems

    SciTech Connect

    Fattebert, J; Law, R J; Bennion, B; Lau, E Y; Schwegler, E; Lightstone, F C

    2009-04-24

    We evaluate the accuracy of density functional theory quantum calculations of biomolecular subsystems using a simple electrostatic embedding scheme. Our scheme is based on dividing the system of interest into a primary and secondary subsystem. A finite difference discretization of the Kohn-Sham equations is used for the primary subsystem, while its electrostatic environment is modeled with a simple one-electron potential. Force-field atomic partial charges are used to generate smeared Gaussian charge densities and to model the secondary subsystem. We illustrate the utility of this approach with calculations of truncated dipeptide chains. We analyze quantitatively the accuracy of this approach by calculating atomic forces and comparing results with fullQMcalculations. The impact of the choice made in terminating dangling bonds at the frontier of the QM region is also investigated.

  6. Frequency-scanning MALDI linear ion trap mass spectrometer for large biomolecular ion detection.

    PubMed

    Lu, I-Chung; Lin, Jung Lee; Lai, Szu-Hsueh; Chen, Chung-Hsuan

    2011-11-01

    This study presents the first report on the development of a matrix-assisted laser desorption ionization (MALDI) linear ion trap mass spectrometer for large biomolecular ion detection by frequency scan. We designed, installed, and tested this radio frequency (RF) scan linear ion trap mass spectrometer and its associated electronics to dramatically extend the mass region to be detected. The RF circuit can be adjusted from 300 to 10 kHz with a set of operation amplifiers. To trap the ions produced by MALDI, a high pressure of helium buffer gas was employed to quench extra kinetic energy of the heavy ions produced by MALDI. The successful detection of the singly charged secretory immunoglobulin A ions indicates that the detectable mass-to-charge ratio (m/z) of this system can reach ~385 000 or beyond. PMID:21932813

  7. Biomolecular and clinical practice in malignant pleural mesothelioma and lung cancer: what thoracic surgeons should know.

    PubMed

    Opitz, Isabelle; Bueno, Raphael; Lim, Eric; Pass, Harvey; Pastorino, Ugo; Boeri, Mattia; Rocco, Gaetano

    2014-10-01

    Today, molecular-profile-directed therapy is a guiding principle of modern thoracic oncology. The knowledge of new biomolecular technology applied to the diagnosis, prognosis, and treatment of lung cancer and mesothelioma should be part of the 21st century thoracic surgeons' professional competence. The European Society of Thoracic Surgeons (ESTS) Biology Club aims at providing a comprehensive insight into the basic biology of the diseases we are treating. During the 2013 ESTS Annual Meeting, different experts of the field presented the current knowledge about diagnostic and prognostic biomarkers in malignant pleural mesothelioma including new perspectives as well as the role and potential application of microRNA and genomic sequencing for lung cancer, which are summarized in the present article. PMID:24623168

  8. Biomolecular and clinical practice in malignant pleural mesothelioma and lung cancer: what thoracic surgeons should know†

    PubMed Central

    Opitz, Isabelle; Bueno, Raphael; Lim, Eric; Pass, Harvey; Pastorino, Ugo; Boeri, Mattia; Rocco, Gaetano

    2014-01-01

    Today, molecular-profile-directed therapy is a guiding principle of modern thoracic oncology. The knowledge of new biomolecular technology applied to the diagnosis, prognosis, and treatment of lung cancer and mesothelioma should be part of the 21st century thoracic surgeons' professional competence. The European Society of Thoracic Surgeons (ESTS) Biology Club aims at providing a comprehensive insight into the basic biology of the diseases we are treating. During the 2013 ESTS Annual Meeting, different experts of the field presented the current knowledge about diagnostic and prognostic biomarkers in malignant pleural mesothelioma including new perspectives as well as the role and potential application of microRNA and genomic sequencing for lung cancer, which are summarized in the present article. PMID:24623168

  9. Structural basis for biomolecular recognition in overlapping binding sites in a diiron enzyme system

    PubMed Central

    Acheson, Justin F.; Bailey, Lucas J.; Elsen, Nathaniel L.; Fox, Brian G.

    2014-01-01

    Productive biomolecular recognition requires exquisite control of affinity and specificity. Accordingly, nature has devised many strategies to achieve proper binding interactions. Bacterial multicomponent monooxygenases provide a fascinating example, where a diiron hydroxylase must reversibly interact with both ferredoxin and catalytic effector in order to achieve electron transfer and O2 activation during catalysis. Because these two accessory proteins have distinct structures, and because the hydroxylase-effector complex covers the entire surface closest to the hydroxylase diiron centre, how ferredoxin binds to the hydroxylase has been unclear. Here we present high-resolution structures of toluene 4-monooxygenase hydroxylase complexed with its electron transfer ferredoxin and compare them with the hydroxylase-effector structure. These structures reveal that ferredoxin or effector protein binding produce different arrangements of conserved residues and customized interfaces on the hydroxylase in order to achieve different aspects of catalysis. PMID:25248368

  10. Application of Neutron Reflectivity for Studies of Biomolecular Structures and Functions at Interfaces

    SciTech Connect

    Johs, Alexander; Liang, Liyuan; Gu, Baohua; Ankner, John Francis; Wang, Wei

    2009-01-01

    Structures and functions of cell membranes are of central importance in understanding processes such as cell signaling, chemotaxis, redox transformation, biofilm formation, and mineralization occurring at interfaces. This chapter provides an overview of the application of neutron reflectivity (NR) as a unique tool for probing biomolecular structures and mechanisms as a first step toward understanding protein protein, protein lipid, and protein mineral interactions at the membrane substrate interfaces. Emphasis is given to the review of existing literature on the assembly of biomimetic membrane systems, such as supported membranes for NR studies, and demonstration of model calculations showing the potential of NR to elucidate molecular fundamentals of microbial cell mineral interactions and structure functional relationships of electron transport pathways. The increased neutron flux afforded by current and upcoming neutron sources holds promise for elucidating detailed processes such as phase separation, formation of microdomains, and membrane interactions with proteins and peptides in biological systems.

  11. Computer programming and biomolecular structure studies: A step beyond internet bioinformatics.

    PubMed

    Likić, 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 approach that relies on access to the Internet and biological databases. This was an ambitious approach considering that the students mostly had a biological background. There were also time constraints of eight lectures in total and two accompanying practical sessions. The main challenge was that students had to be introduced to computer programming from a beginner level and in a short time provided with enough knowledge to independently solve a simple bioinformatics problem. This was accomplished with a problem directly relevant to the rest of the subject, concerned with the structure-function relationships and experimental techniques for the determination of macromolecular structure. PMID:21638623

  12. Overcoming the Solubility Limit with Solubility-Enhancement Tags: Successful Applications in Biomolecular NMR Studies

    PubMed Central

    Zhou, Pei; Wagner, Gerhard

    2010-01-01

    Although the rapid progress of NMR technology has significantly expanded the range of NMR-trackable systems, preparation of NMR-suitable samples that are highly soluble and stable remains a bottleneck for studies of many biological systems. The application of solubility-enhancement tags (SETs) has been highly effective in overcoming solubility and sample stability issues and has enabled structural studies of important biological systems previously deemed unapproachable by solution NMR techniques. In this review, we provide a brief survey of the development and successful applications of the SET strategy in biomolecular NMR. We also comment on the criteria for choosing optimal SETs, such as for differently charged target proteins, and recent new developments on NMR-invisible SETs. PMID:19731047

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

    PubMed Central

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

    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 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. PMID:23999588

  14. Quantum dynamics of electronic excitations in biomolecular chromophores: role of the protein environment and solvent.

    PubMed

    Gilmore, Joel; McKenzie, Ross H

    2008-03-20

    A biomolecular chromophore can be viewed as a quantum system with a small number of degrees of freedom interacting with an environment (the surrounding protein and solvent) which has many degrees of freedom, the majority of which can be described classically. The system-environment interaction can be described by a spectral density for a spin-boson model. The quantum dynamics of electronic excitations in the chromophore are completely determined by this spectral density, which is of great interest for describing quantum decoherence and quantum measurements. Specifically, the spectral density determines the time scale for the "collapse" of the wave function of the chromophore due to continuous measurement of its quantum state by the environment. Although of fundamental interest, there very few physical systems for which the spectral density has been determined experimentally and characterized. In contrast, here, we give the parameters for the spectral densities for a wide range of chromophores, proteins, and solvents. Expressions for the spectral density are derived for continuum dielectric models of the chromophore environment. There are contributions to the spectral density from each component of the environment: the protein, the water bound to the protein, and the bulk solvent. Each component affects the quantum dynamics of the chromophore on distinctly different time scales. Our results provide a natural description of the different time scales observed in ultrafast laser spectroscopy, including three pulse photon echo decay and dynamic Stokes shift measurements. We show that even if the chromophore is well separated from the solvent by the surrounding protein, ultrafast solvation can be still be dominated by the solvent. Consequently, we suggest that the subpicosecond solvation observed in some biomolecular chromophores should not necessarily be assigned to ultrafast protein dynamics. The magnitude of the chromophore-environment coupling is sufficiently strong

  15. Surface chemistry for stable and smart molecular and biomolecular interfaces via photochemical grafting of alkenes.

    PubMed

    Wang, Xiaoyu; Landis, Elizabeth C; Franking, Ryan; Hamers, Robert J

    2010-09-21

    Many emerging fields such as biotechnology and renewable energy require functionalized surfaces that are "smart" and highly stable. Surface modification schemes developed previously have often been limited to simple molecules or have been based on weakly bound layers that have limited stability. In this Account, we report on recent developments enabling the preparation of molecular and biomolecular interfaces that exhibit high selectivity and unprecedented stability on a range of covalent materials including diamond, vertically aligned carbon nanofibers, silicon, and metal oxides. One particularly successful pathway to ultrastable interfaces involves the photochemical grafting of organic alkenes to the surfaces. Bifunctional alkenes with a suitable functional group at the distal end can directly impart functionality and can serve as attachment points for linking complex structures such as DNA and proteins. The successful application of photochemical grafting to a surprisingly wide range of materials has motivated researchers to better understand the underlying photochemical reaction mechanisms. The resulting studies using experimental and computational methods have provided fundamental insights into the electronic structure of the molecules and the surface control photochemical reactivity. Such investigations have revealed the important role of a previously unrecognized process, photoelectron emission, in initiating photochemical grafting of alkenes to surfaces. Molecular and biomolecular interfaces formed on diamond and other covalent materials are leading to novel types of molecular electronic interfaces. For example, electrical, optical, or electromechanical structures that convert biological information directly into analytical signals allow for direct label-free detection of DNA and proteins. Because of the preferential adherence of molecules to graphitic edge-plane sites, the grafting of redox-active species to vertically aligned carbon nanofibers leads to

  16. Graph-theoretical identification of dissociation pathways on free energy landscapes of biomolecular interaction.

    PubMed

    Wang, Ling; Stumm, Boris; Helms, Volkhard

    2010-03-01

    Biomolecular association and dissociation reactions take place on complicated interaction free energy landscapes that are still very hard to characterize computationally. For large enough distances, though, it often suffices to consider the six relative translational and rotational degrees of freedom of the two particles treated as rigid bodies. Here, we computed the six-dimensional free energy surface of a dimer of water-soluble alpha-helices by scanning these six degrees of freedom in about one million grid points. In each point, the relative free energy difference was computed as the sum of the polar and nonpolar solvation free energies of the helix dimer and of the intermolecular coulombic interaction energy. The Dijkstra graph algorithm was then applied to search for the lowest cost dissociation pathways based on a weighted, directed graph, where the vertices represent the grid points, the edges connect the grid points and their neighbors, and the weights are the reaction costs between adjacent pairs of grid points. As an example, the configuration of the bound state was chosen as the source node, and the eight corners of the translational cube were chosen as the destination nodes. With the strong electrostatic interaction of the two helices giving rise to a clearly funnel-shaped energy landscape, the eight lowest-energy cost pathways coming from different orientations converge into a well-defined pathway for association. We believe that the methodology presented here will prove useful for identifying low-energy association and dissociation pathways in future studies of complicated free energy landscapes for biomolecular interaction. PMID:19603501

  17. A CMOS wireless biomolecular sensing system-on-chip based on polysilicon nanowire technology.

    PubMed

    Huang, C-W; Huang, Y-J; Yen, P-W; Tsai, H-H; Liao, H-H; Juang, Y-Z; Lu, S-S; Lin, C-T

    2013-11-21

    As developments of modern societies, an on-field and personalized diagnosis has become important for disease prevention and proper treatment. To address this need, in this work, a polysilicon nanowire (poly-Si NW) based biosensor system-on-chip (bio-SSoC) is designed and fabricated by a 0.35 μm 2-Poly-4-Metal (2P4M) complementary metal-oxide-semiconductor (CMOS) process provided by a commercialized semiconductor foundry. Because of the advantages of CMOS system-on-chip (SoC) technologies, the poly-Si NW biosensor is integrated with a chopper differential-difference amplifier (DDA) based analog-front-end (AFE), a successive approximation analog-to-digital converter (SAR ADC), and a microcontroller to have better sensing capabilities than a traditional Si NW discrete measuring system. In addition, an on-off key (OOK) wireless transceiver is also integrated to form a wireless bio-SSoC technology. This is pioneering work to harness the momentum of CMOS integrated technology into emerging bio-diagnosis technologies. This integrated technology is experimentally examined to have a label-free and low-concentration biomolecular detection for both Hepatitis B Virus DNA (10 fM) and cardiac troponin I protein (3.2 pM). Based on this work, the implemented wireless bio-SSoC has demonstrated a good biomolecular sensing characteristic and a potential for low-cost and mobile applications. As a consequence, this developed technology can be a promising candidate for on-field and personalized applications in biomedical diagnosis. PMID:24080725

  18. Fundamental properties and atmospheric structure of the red supergiant VY Canis Majoris based on VLTI/AMBER spectro-interferometry

    NASA Astrophysics Data System (ADS)

    Wittkowski, M.; Hauschildt, P. H.; Arroyo-Torres, B.; Marcaide, J. M.

    2012-04-01

    Aims: We investigate the atmospheric structure and fundamental properties of the red supergiant VY CMa. Methods: We obtained near-infrared spectro-interferometric observations of VY CMa with spectral resolutions of 35 and 1500 using the AMBER instrument at the VLTI. Results: The visibility data indicate the presence of molecular layers of water vapor and CO in the extended atmosphere with an asymmetric morphology. The uniform disk diameter in the water band around 2.0 μm is increased by ~20% compared to the near-continuum bandpass at 2.20-2.25 μm, and in the CO band at 2.3-2.5 μm it is increased by up to ~50%. The closure phases indicate relatively small deviations from point symmetry close to the photospheric layer, and stronger deviations in the extended H2O and CO layers. Making use of the high spatial and spectral resolution, a near-continuum bandpass can be isolated from contamination by molecular and dusty layers, and the Rosseland-mean photospheric angular diameter is estimated to 11.3 ± 0.3 mas based on a PHOENIX atmosphere model. Together with recent high-precision estimates of the distance and spectro-photometry, this estimate corresponds to a radius of 1420 ± 120 R⊙ and an effective temperature of 3490 ± 90 K. Conclusions: VY CMa exhibits asymmetric, possibly clumpy, atmospheric layers of H2O and CO, which are not co-spatial, within a larger elongated dusty envelope. Our revised fundamental parameters put VY CMa close to the Hayashi limit of recent evolutionary tracks of initial mass 25 M⊙ with rotation or 32 M⊙ without rotation, shortly before evolving blueward in the HR-diagram. Based on observations made with the VLT Interferometer (VLTI) at Paranal Observatory under programme ID 386.D-0012.Figures 2, 3 and 5 are available in electronic form at http://www.aanda.org

  19. A Collaborative Study of the Etiology of Breast Cancer Subtypes in African American Women: the AMBER Consortium

    PubMed Central

    Palmer, Julie R.; Ambrosone, Christine B.; Olshan, Andrew F.

    2014-01-01

    Purpose Breast cancer is a heterogeneous disease, with at least five intrinsic subtypes defined by molecular characteristics. Tumors that express the estrogen receptor (ER+) have better outcomes than ER− tumors, due in part to the success of hormonal therapies that target ER+ tumors. The incidence of ER− breast cancer, and the subset of ER− cancers that are basal-like, is about twice as high among African American (AA) women as among U.S. women of European descent (EA). This disparity appears to explain, in part, the disproportionately high mortality from breast cancer that occurs in AA women. Epidemiologic research on breast cancer in AA women lags behind research in EA women. Here, we review differences in the etiology of breast cancer subtypes among AA women and describe a new consortium of ongoing studies of breast cancer in AA women. Methods We combined samples and data from four large epidemiologic studies of breast cancer in AA women, two cohort and two case-control, creating the AMBER consortium. Tumor tissue is obtained and stored in tissue microarrays, with assays of molecular markers carried out at a pathology core. Genotyping, carried out centrally, includes a whole exome SNP array and over 180,000 custom SNPs for fine-mapping of GWAS loci and candidate pathways. Results To date, questionnaire data from 5,739 breast cancer cases and 14,273 controls have been harmonized. Genotyping of the first 3,200 cases and 3,700 controls is underway, with a total of 6,000 each expected by the end of the study period. Conclusions The new consortium will likely have sufficient statistical power to assess potential risk factors, both genetic and non-genetic in relation to specific subtypes of breast cancer in AA women. PMID:24343304

  20. Genetic variations in vitamin D-related pathways and breast cancer risk in African American women in the AMBER consortium.

    PubMed

    Yao, Song; Haddad, Stephen A; Hu, Qiang; Liu, Song; Lunetta, Kathryn L; Ruiz-Narvaez, Edward A; Hong, Chi-Chen; Zhu, Qianqian; Sucheston-Campbell, Lara; Cheng, Ting-Yuan David; Bensen, Jeannette T; Johnson, Candace S; Trump, Donald L; Haiman, Christopher A; Olshan, Andrew F; Palmer, Julie R; Ambrosone, Christine B

    2016-05-01

    Studies of genetic variations in vitamin D-related pathways and breast cancer risk have been conducted mostly in populations of European ancestry, and only sparsely in African Americans (AA), who are known for a high prevalence of vitamin D deficiency. We analyzed 24,445 germline variants in 63 genes from vitamin D-related pathways in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium, including 3,663 breast cancer cases and 4,687 controls. Odds ratios (OR) were derived from logistic regression models for overall breast cancer, by estrogen receptor (ER) status (1,983 ER positive and 1,098 ER negative), and for case-only analyses of ER status. None of the three vitamin D-related pathways were associated with breast cancer risk overall or by ER status. Gene-level analyses identified associations with risk for several genes at a nominal p ≤ 0.05, particularly for ER- breast cancer, including rs4647707 in DDB2. In case-only analyses, vitamin D metabolism and signaling pathways were associated with ER- cancer (pathway-level p = 0.02), driven by a single gene CASR (gene-level p = 0.001). The top SNP in CASR was rs112594756 (p = 7 × 10(-5), gene-wide corrected p = 0.01), followed by a second signal from a nearby SNP rs6799828 (p = 1 × 10(-4), corrected p = 0.03). In summary, several variants in vitamin D pathways were associated with breast cancer risk in AA women. In addition, CASR may be related to tumor ER status, supporting a role of vitamin D or calcium in modifying breast cancer phenotypes. PMID:26650177