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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 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

  15. 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

  16. 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.

  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 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

  2. 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

  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. 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

  19. 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

  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

    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

  8. 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

  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. 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

  12. 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

  13. 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

  14. 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

  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. 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

  19. 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.

  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. 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

  12. 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.

  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. 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.

  16. 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.

  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. 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. ...

  19. 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

  20. 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.

  1. 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

  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 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

  4. 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

  5. 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

  6. 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

  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. 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

  10. 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.

  11. 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

  12. 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

  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. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  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. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  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 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

  4. 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

  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. 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

  9. 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

  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. 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.

  12. 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.

  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. 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

  18. 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

  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. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  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. 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

  18. 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

  19. 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

  20. 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

  1. 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

  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. 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.

  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. 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

  8. 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

  9. 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.

  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. 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

  1. 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

  2. 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.

  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

    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

  8. 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

  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. 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

  11. 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…

  12. 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

  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. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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…

  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 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

  8. 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

  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