Sequential backbone assignment based on dipolar amide-to-amide correlation experiments

International Nuclear Information System (INIS)

Xiang, ShengQi; Grohe, Kristof; Rovó, Petra; Vasa, Suresh Kumar; Giller, Karin; Becker, Stefan; Linser, Rasmus

2015-01-01

Proton detection in solid-state NMR has seen a tremendous increase in popularity in the last years. New experimental techniques allow to exploit protons as an additional source of information on structure, dynamics, and protein interactions with their surroundings. In addition, sensitivity is mostly improved and ambiguity in assignment experiments reduced. We show here that, in the solid state, sequential amide-to-amide correlations turn out to be an excellent, complementary way to exploit amide shifts for unambiguous backbone assignment. For a general assessment, we compare amide-to-amide experiments with the more common 13 C-shift-based methods. Exploiting efficient CP magnetization transfers rather than less efficient INEPT periods, our results suggest that the approach is very feasible for solid-state NMR

Trappist: european project dedicated to an open backbone structure for NDT expertise

International Nuclear Information System (INIS)

Nouailhas, B.; Vailhen, O.

1993-01-01

Non Destructive Testing (NDT) on critical components such as the reactor vessel, primary coolant pipes and steam generators have already been, and are still the subject of many development concerning the improvement of measuring techniques, data processing and on site operation. The tools developed for these tests are generally closed, difficult to extend and of proprietary type. Productivity could be increased if an open backbone structure common to several types of test were available. Moreover, these components are generally submitted to a test involving a single method. In certain cases, the produced information is an insufficient basis for drawing up a satisfactory diagnosis: the test operator or expert often faces problems in extracting more information from signals that are generally noisy. It may prove necessary to complete the inspection with another NDT method based on different principles in order to obtain better performances. It is then by combining the information obtained by two complementary methods that it will be possible to draw up a more reliable diagnosis. These components have also a complex shape. In the case of ultrasonic testing, the accurate following of probe paths requires 3D representation of the geometry, as it is built, to position and display the data obtained from the inspection. To take these geometric constraints into account, it is imperative to use computer tools allowing the three-dimensional representation of the reconstructed information on the components' actual geometry. This specific difficulty, which has long been appreciated, is the subject of developments resulting to industrial products that are more or less satisfactory. The aim of the European Project TRAPPIST (Race Program) is to study an open backbone structure. A mock-up of an analysis station dedicated to NDT expertise will be built and evaluated with specific examples. (authors). 6 figs., 1 ref

A rapid NMR-based method for discrimination of strain-specific cell wall teichoic acid structures reveals a third backbone type in Lactobacillus plantarum.

Science.gov (United States)

Tomita, Satoru; Tanaka, Naoto; Okada, Sanae

2017-03-01

The lactic acid bacterium Lactobacillus plantarum is capable of producing strain-specific structures of cell wall teichoic acid (WTA), an anionic polysaccharide found in the Gram-positive bacterial cell wall. In this study, we established a rapid, NMR-based procedure to discriminate WTA structures in this species, and applied it to 94 strains of L. plantarum. Six previously reported glycerol- and ribitol-containing WTA subtypes were successfully identified from 78 strains, suggesting that these were the dominant structures. However, the level of structural variety differed markedly among bacterial sources, possibly reflecting differences in strain-level microbial diversity. WTAs from eight strains were not identified based on NMR spectra and were classified into three groups. Structural analysis of a partial degradation product of an unidentified WTA produced by strain TUA 1496L revealed that the WTA was 1-O-β-d-glucosylglycerol. Two-dimensional NMR analysis of the polymer structure showed phosphodiester bonds between C-3 and C-6 of the glycerol and glucose residues, suggesting a polymer structure of 3,6΄-linked poly(1-O-β-d-glucosyl-sn-glycerol phosphate). This is the third WTA backbone structure in L. plantarum, following 3,6΄-linked poly(1-O-α-d-glucosyl-sn-glycerol phosphate) and 1,5-linked poly(ribitol phosphate). © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

High Performance Infiltrated Backbones for Cathode-Supported SOFC's

DEFF Research Database (Denmark)

Gil, Vanesa; Kammer Hansen, Kent

2014-01-01

The concept of using highly ionic conducting backbones with subsequent infiltration of electronically conducting particles has widely been used to develop alternative anode-supported SOFC's. In this work, the idea was to develop infiltrated backbones as an alternative design based on cathode......, microstructural characterization and electrochemical testing are discussed. Data on polarization resistance, Rp, are obtained from impedance spectra recorded on quasi-symmetrical cells (YSZ backbones/YSZ/LSM-YSZ (screen printed)). The backbones are infiltrated with LSM and compared to a standard LSM-YSZ screen...

Underestimated Halogen Bonds Forming with Protein Backbone in Protein Data Bank.

Science.gov (United States)

Zhang, Qian; Xu, Zhijian; Shi, Jiye; Zhu, Weiliang

2017-07-24

Halogen bonds (XBs) are attracting increasing attention in biological systems. Protein Data Bank (PDB) archives experimentally determined XBs in biological macromolecules. However, no software for structure refinement in X-ray crystallography takes into account XBs, which might result in the weakening or even vanishing of experimentally determined XBs in PDB. In our previous study, we showed that side-chain XBs forming with protein side chains are underestimated in PDB on the basis of the phenomenon that the proportion of side-chain XBs to overall XBs decreases as structural resolution becomes lower and lower. However, whether the dominant backbone XBs forming with protein backbone are overlooked is still a mystery. Here, with the help of the ratio (R F ) of the observed XBs' frequency of occurrence to their frequency expected at random, we demonstrated that backbone XBs are largely overlooked in PDB, too. Furthermore, three cases were discovered possessing backbone XBs in high resolution structures while losing the XBs in low resolution structures. In the last two cases, even at 1.80 Å resolution, the backbone XBs were lost, manifesting the urgent need to consider XBs in the refinement process during X-ray crystallography study.

Influence of structures of polymer backbones on cooperative photoreorientation behavior of p-cyanoazobenzene side chains

DEFF Research Database (Denmark)

Han, Mina; Kidowaki, Masatoshi; Ichimura, Kunihiro

2001-01-01

Photoinduced orientational behavior of a polymethacrylate (CN6) and a polyester (p6a12) with p-cyanoazobenzene side chains was studied to reveal the structural effect of the liquid crystalline polymer backbones. Irradiation with linearly polarized W light resulted in the reorientation of the azob...

Correlation between protein secondary structure, backbone bond angles, and side-chain orientations

Science.gov (United States)

Lundgren, Martin; Niemi, Antti J.

2012-08-01

We investigate the fine structure of the sp3 hybridized covalent bond geometry that governs the tetrahedral architecture around the central Cα carbon of a protein backbone, and for this we develop new visualization techniques to analyze high-resolution x-ray structures in the Protein Data Bank. We observe that there is a correlation between the deformations of the ideal tetrahedral symmetry and the local secondary structure of the protein. We propose a universal coarse-grained energy function to describe the ensuing side-chain geometry in terms of the Cβ carbon orientations. The energy function can model the side-chain geometry with a subatomic precision. As an example we construct the Cα-Cβ structure of HP35 chicken villin headpiece. We obtain a configuration that deviates less than 0.4 Å in root-mean-square distance from the experimental x-ray structure.

APSY-NMR for protein backbone assignment in high-throughput structural biology

Energy Technology Data Exchange (ETDEWEB)

Dutta, Samit Kumar; Serrano, Pedro; Proudfoot, Andrew; Geralt, Michael [The Scripps Research Institute, Department of Integrative Structural and Computational Biology (United States); Pedrini, Bill [Paul Scherrer Institute (PSI), SwissFEL Project (Switzerland); Herrmann, Torsten [Université de Lyon, Institut des Sciences Analytiques, Centre de RMN à Très Hauts Champs, UMR 5280 CNRS, ENS Lyon, UCB Lyon 1 (France); Wüthrich, Kurt, E-mail: wuthrich@scripps.edu [The Scripps Research Institute, Department of Integrative Structural and Computational Biology (United States)

2015-01-15

A standard set of three APSY-NMR experiments has been used in daily practice to obtain polypeptide backbone NMR assignments in globular proteins with sizes up to about 150 residues, which had been identified as targets for structure determination by the Joint Center for Structural Genomics (JCSG) under the auspices of the Protein Structure Initiative (PSI). In a representative sample of 30 proteins, initial fully automated data analysis with the software UNIO-MATCH-2014 yielded complete or partial assignments for over 90 % of the residues. For most proteins the APSY data acquisition was completed in less than 30 h. The results of the automated procedure provided a basis for efficient interactive validation and extension to near-completion of the assignments by reference to the same 3D heteronuclear-resolved [{sup 1}H,{sup 1}H]-NOESY spectra that were subsequently used for the collection of conformational constraints. High-quality structures were obtained for all 30 proteins, using the J-UNIO protocol, which includes extensive automation of NMR structure determination.

Versatile phosphite ligands based on silsesquioxane backbones

NARCIS (Netherlands)

van der Vlugt, JI; Ackerstaff, J; Dijkstra, TW; Mills, AM; Kooijman, H; Spek, AL; Meetsma, A; Abbenhuis, HCL; Vogt, D

Silsesquioxanes are employed as ligand backbones for the synthesis of novel phosphite compounds with 3,3'-5,5'-tetrakis(tert-butyl)-2,2'-di-oxa-1,1'-biphenyl substituents. Both mono- and bidentate phosphites are prepared in good yields. Two types of silsesquioxanes are employed as starting

Combining automated peak tracking in SAR by NMR with structure-based backbone assignment from 15N-NOESY

KAUST Repository

Jang, Richard; Gao, Xin; Li, Ming

2012-01-01

Background: Chemical shift mapping is an important technique in NMR-based drug screening for identifying the atoms of a target protein that potentially bind to a drug molecule upon the molecule's introduction in increasing concentrations. The goal is to obtain a mapping of peaks with known residue assignment from the reference spectrum of the unbound protein to peaks with unknown assignment in the target spectrum of the bound protein. Although a series of perturbed spectra help to trace a path from reference peaks to target peaks, a one-to-one mapping generally is not possible, especially for large proteins, due to errors, such as noise peaks, missing peaks, missing but then reappearing, overlapped, and new peaks not associated with any peaks in the reference. Due to these difficulties, the mapping is typically done manually or semi-automatically, which is not efficient for high-throughput drug screening.Results: We present PeakWalker, a novel peak walking algorithm for fast-exchange systems that models the errors explicitly and performs many-to-one mapping. On the proteins: hBclXL, UbcH5B, and histone H1, it achieves an average accuracy of over 95% with less than 1.5 residues predicted per target peak. Given these mappings as input, we present PeakAssigner, a novel combined structure-based backbone resonance and NOE assignment algorithm that uses just 15N-NOESY, while avoiding TOCSY experiments and 13C-labeling, to resolve the ambiguities for a one-to-one mapping. On the three proteins, it achieves an average accuracy of 94% or better.Conclusions: Our mathematical programming approach for modeling chemical shift mapping as a graph problem, while modeling the errors directly, is potentially a time- and cost-effective first step for high-throughput drug screening based on limited NMR data and homologous 3D structures. 2012 Jang et al.; licensee BioMed Central Ltd.

Combining automated peak tracking in SAR by NMR with structure-based backbone assignment from 15N-NOESY

KAUST Repository

Jang, Richard

2012-03-21

Background: Chemical shift mapping is an important technique in NMR-based drug screening for identifying the atoms of a target protein that potentially bind to a drug molecule upon the molecule\\'s introduction in increasing concentrations. The goal is to obtain a mapping of peaks with known residue assignment from the reference spectrum of the unbound protein to peaks with unknown assignment in the target spectrum of the bound protein. Although a series of perturbed spectra help to trace a path from reference peaks to target peaks, a one-to-one mapping generally is not possible, especially for large proteins, due to errors, such as noise peaks, missing peaks, missing but then reappearing, overlapped, and new peaks not associated with any peaks in the reference. Due to these difficulties, the mapping is typically done manually or semi-automatically, which is not efficient for high-throughput drug screening.Results: We present PeakWalker, a novel peak walking algorithm for fast-exchange systems that models the errors explicitly and performs many-to-one mapping. On the proteins: hBclXL, UbcH5B, and histone H1, it achieves an average accuracy of over 95% with less than 1.5 residues predicted per target peak. Given these mappings as input, we present PeakAssigner, a novel combined structure-based backbone resonance and NOE assignment algorithm that uses just 15N-NOESY, while avoiding TOCSY experiments and 13C-labeling, to resolve the ambiguities for a one-to-one mapping. On the three proteins, it achieves an average accuracy of 94% or better.Conclusions: Our mathematical programming approach for modeling chemical shift mapping as a graph problem, while modeling the errors directly, is potentially a time- and cost-effective first step for high-throughput drug screening based on limited NMR data and homologous 3D structures. 2012 Jang et al.; licensee BioMed Central Ltd.

The extension of a DNA double helix by an additional Watson-Crick base pair on the same backbone

DEFF Research Database (Denmark)

Kumar, P.; Sharma, P. K.; Madsen, Charlotte S.

2013-01-01

Additional base pair: The DNA duplex can be extended with an additional Watson-Crick base pair on the same backbone by the use of double-headed nucleotides. These also work as compressed dinucleotides and form two base pairs with cognate nucleobases on the opposite strand.......Additional base pair: The DNA duplex can be extended with an additional Watson-Crick base pair on the same backbone by the use of double-headed nucleotides. These also work as compressed dinucleotides and form two base pairs with cognate nucleobases on the opposite strand....

Adding diverse noncanonical backbones to rosetta: enabling peptidomimetic design.

Directory of Open Access Journals (Sweden)

Kevin Drew

Full Text Available Peptidomimetics are classes of molecules that mimic structural and functional attributes of polypeptides. Peptidomimetic oligomers can frequently be synthesized using efficient solid phase synthesis procedures similar to peptide synthesis. Conformationally ordered peptidomimetic oligomers are finding broad applications for molecular recognition and for inhibiting protein-protein interactions. One critical limitation is the limited set of design tools for identifying oligomer sequences that can adopt desired conformations. Here, we present expansions to the ROSETTA platform that enable structure prediction and design of five non-peptidic oligomer scaffolds (noncanonical backbones, oligooxopiperazines, oligo-peptoids, [Formula: see text]-peptides, hydrogen bond surrogate helices and oligosaccharides. This work is complementary to prior additions to model noncanonical protein side chains in ROSETTA. The main purpose of our manuscript is to give a detailed description to current and future developers of how each of these noncanonical backbones was implemented. Furthermore, we provide a general outline for implementation of new backbone types not discussed here. To illustrate the utility of this approach, we describe the first tests of the ROSETTA molecular mechanics energy function in the context of oligooxopiperazines, using quantum mechanical calculations as comparison points, scanning through backbone and side chain torsion angles for a model peptidomimetic. Finally, as an example of a novel design application, we describe the automated design of an oligooxopiperazine that inhibits the p53-MDM2 protein-protein interaction. For the general biological and bioengineering community, several noncanonical backbones have been incorporated into web applications that allow users to freely and rapidly test the presented protocols (http://rosie.rosettacommons.org. This work helps address the peptidomimetic community's need for an automated and expandable

Automated backbone assignment of labeled proteins using the threshold accepting algorithm

International Nuclear Information System (INIS)

Leutner, Michael; Gschwind, Ruth M.; Liermann, Jens; Schwarz, Christian; Gemmecker, Gerd; Kessler, Horst

1998-01-01

The sequential assignment of backbone resonances is the first step in the structure determination of proteins by heteronuclear NMR. For larger proteins, an assignment strategy based on proton side-chain information is no longer suitable for the use in an automated procedure. Our program PASTA (Protein ASsignment by Threshold Accepting) is therefore designed to partially or fully automate the sequential assignment of proteins, based on the analysis of NMR backbone resonances plus C β information. In order to overcome the problems caused by peak overlap and missing signals in an automated assignment process, PASTA uses threshold accepting, a combinatorial optimization strategy, which is superior to simulated annealing due to generally faster convergence and better solutions. The reliability of this algorithm is shown by reproducing the complete sequential backbone assignment of several proteins from published NMR data. The robustness of the algorithm against misassigned signals, noise, spectral overlap and missing peaks is shown by repeating the assignment with reduced sequential information and increased chemical shift tolerances. The performance of the program on real data is finally demonstrated with automatically picked peak lists of human nonpancreatic synovial phospholipase A 2 , a protein with 124 residues

Nonribosomal biosynthesis of backbone-modified peptides

Science.gov (United States)

Niquille, David L.; Hansen, Douglas A.; Mori, Takahiro; Fercher, David; Kries, Hajo; Hilvert, Donald

2018-03-01

Biosynthetic modification of nonribosomal peptide backbones represents a potentially powerful strategy to modulate the structure and properties of an important class of therapeutics. Using a high-throughput assay for catalytic activity, we show here that an L-Phe-specific module of an archetypal nonribosomal peptide synthetase can be reprogrammed to accept and process the backbone-modified amino acid (S)-β-Phe with near-native specificity and efficiency. A co-crystal structure with a non-hydrolysable aminoacyl-AMP analogue reveals the origins of the 40,000-fold α/β-specificity switch, illuminating subtle but precise remodelling of the active site. When the engineered catalyst was paired with downstream module(s), (S)-β-Phe-containing peptides were produced at preparative scale in vitro (~1 mmol) and high titres in vivo (~100 mg l-1), highlighting the potential of biosynthetic pathway engineering for the construction of novel nonribosomal β-frameworks.

Induced helical backbone conformations of self-organizable dendronized polymers.

Science.gov (United States)

Rudick, Jonathan G; Percec, Virgil

2008-12-01

Control of function through the primary structure of a molecule presents a significant challenge with valuable rewards for nanoscience. Dendritic building blocks encoded with information that defines their three-dimensional shape (e.g., flat-tapered or conical) and how they associate with each other are referred to as self-assembling dendrons. Self-organizable dendronized polymers possess a flat-tapered or conical self-assembling dendritic side chain on each repeat unit of a linear polymer backbone. When appended to a covalent polymer, the self-assembling dendrons direct a folding process (i.e., intramolecular self-assembly). Alternatively, intermolecular self-assembly of dendrons mediated by noncovalent interactions between apex groups can generate a supramolecular polymer backbone. Self-organization, as we refer to it, is the spontaneous formation of periodic and quasiperiodic arrays from supramolecular elements. Covalent and supramolecular polymers jacketed with self-assembling dendrons self-organize. The arrays are most often comprised of cylindrical or spherical objects. The shape of the object is determined by the primary structure of the dendronized polymer: the structure of the self-assembling dendron and the length of the polymer backbone. It is therefore possible to predictably generate building blocks for single-molecule nanotechnologies or arrays of supramolecules for bottom-up self-assembly. We exploit the self-organization of polymers jacketed with self-assembling dendrons to elucidate how primary structure determines the adopted conformation and fold (i.e., secondary and tertiary structure), how the supramolecules associate (i.e., quaternary structure), and their resulting functions. A combination of experimental techniques is employed to interrogate the primary, secondary, tertiary, and quaternary structure of the self-organizable dendronized polymers. We refer to the process by which we interpolate between the various levels of structural

Combining ambiguous chemical shift mapping with structure-based backbone and NOE assignment from 15N-NOESY

KAUST Repository

Jang, Richard

2011-01-01

Chemical shift mapping is an important technique in NMRbased drug screening for identifying the atoms of a target protein that potentially bind to a drug molecule upon the molecule\\'s introduction in increasing concentrations. The goal is to obtain a mapping of peaks with known residue assignment from the reference spectrum of the unbound protein to peaks with unknown assignment in the target spectrum of the bound protein. Although a series of perturbed spectra help to trace a path from reference peaks to target peaks, a one-to-one mapping generally is not possible, especially for large proteins, due to errors, such as noise peaks, missing peaks, missing but then reappearing, overlapped, and new peaks not associated with any peaks in the reference. Due to these difficulties, the mapping is typically done manually or semi-automatically. However, automated methods are necessary for high-throughput drug screening. We present PeakWalker, a novel peak walking algorithm for fast-exchange systems that models the errors explicitly and performs many-to-one mapping. On the proteins: hBclXL, UbcH5B, and histone H1, it achieves an average accuracy of over 95% with less than 1.5 residues predicted per target peak. Given these mappings as input, we present PeakAssigner, a novel combined structure-based backbone resonance and NOE assignment algorithm that uses just 15N-NOESY, while avoiding TOCSY experiments and 13C- labeling, to resolve the ambiguities for a one-toone mapping. On the three proteins, it achieves an average accuracy of 94% or better. Copyright © 2011 ACM.

Testing Backbone.js

CERN Document Server

Roemer, Ryan

2013-01-01

This book is packed with the step by step tutorial and instructions in recipe format helping you setup test infrastructure and gradually advance your skills to plan, develop, and test your backbone applications.If you are a JavaScript developer looking for recipes to create and implement test support for your backbone application, then this book is ideal for you.

1990s: High Capacity Backbones

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. 1990s: High Capacity Backbones. Backbone capacities increased from 2.5 Gb/s to 100s of Gb/s during the 1990's. Wavelength division multiplexing with 160 waves of 10 Gb/s was commercially available. Several high-capacity backbones built in the US and Europe.

Determination of protein global folds using backbone residual dipolar coupling and long-range NOE restraints

International Nuclear Information System (INIS)

Giesen, Alexander W.; Homans, Steve W.; Brown, Jonathan Miles

2003-01-01

We report the determination of the global fold of human ubiquitin using protein backbone NMR residual dipolar coupling and long-range nuclear Overhauser effect (NOE) data as conformational restraints. Specifically, by use of a maximum of three backbone residual dipolar couplings per residue (N i -H N i , N i -C' i-1 , H N i - C' i-1 ) in two tensor frames and only backbone H N -H N NOEs, a global fold of ubiquitin can be derived with a backbone root-mean-square deviation of 1.4 A with respect to the crystal structure. This degree of accuracy is more than adequate for use in databases of structural motifs, and suggests a general approach for the determination of protein global folds using conformational restraints derived only from backbone atoms

Backbone amide linker strategy

DEFF Research Database (Denmark)

Shelton, Anne Pernille Tofteng; Jensen, Knud Jørgen

2013-01-01

In the backbone amide linker (BAL) strategy, the peptide is anchored not at the C-terminus but through a backbone amide, which leaves the C-terminal available for various modifications. This is thus a very general strategy for the introduction of C-terminal modifications. The BAL strategy...

Coupling between myosin head conformation and the thick filament backbone structure.

Science.gov (United States)

Hu, Zhongjun; Taylor, Dianne W; Edwards, Robert J; Taylor, Kenneth A

2017-12-01

The recent high-resolution structure of the thick filament from Lethocerus asynchronous flight muscle shows aspects of thick filament structure never before revealed that may shed some light on how striated muscles function. The phenomenon of stretch activation underlies the function of asynchronous flight muscle. It is most highly developed in flight muscle, but is also observed in other striated muscles such as cardiac muscle. Although stretch activation is likely to be complex, involving more than a single structural aspect of striated muscle, the thick filament itself, would be a prime site for regulatory function because it must bear all of the tension produced by both its associated myosin motors and any externally applied force. Here we show the first structural evidence that the arrangement of myosin heads within the interacting heads motif is coupled to the structure of the thick filament backbone. We find that a change in helical angle of 0.16° disorders the blocked head preferentially within the Lethocerus interacting heads motif. This observation suggests a mechanism for how tension affects the dynamics of the myosin heads leading to a detailed hypothesis for stretch activation and shortening deactivation, in which the blocked head preferentially binds the thin filament followed by the free head when force production occurs. Copyright © 2017 Elsevier Inc. All rights reserved.

CORBA and MPI-based 'backbone' for coupling advanced simulation tools

International Nuclear Information System (INIS)

Seydaliev, M.; Caswell, D.

2014-01-01

There is a growing international interest in using coupled, multidisciplinary computer simulations for a variety of purposes, including nuclear reactor safety analysis. Reactor behaviour can be modeled using a suite of computer programs simulating phenomena or predicting parameters that can be categorized into disciplines such as Thermalhydraulics, Neutronics, Fuel, Fuel Channels, Fission Product Release and Transport, Containment and Atmospheric Dispersion, and Severe Accident Analysis. Traditionally, simulations used for safety analysis individually addressed only the behaviour within a single discipline, based upon static input data from other simulation programs. The limitation of using a suite of stand-alone simulations is that phenomenological interdependencies or temporal feedback between the parameters calculated within individual simulations cannot be adequately captured. To remove this shortcoming, multiple computer simulations for different disciplines must exchange data during runtime to address these interdependencies. This article describes the concept of a new framework, which we refer to as the 'Backbone', to provide the necessary runtime exchange of data. The Backbone, currently under development at AECL for a preliminary feasibility study, is a hybrid design using features taken from the Common Object Request Broker Architecture (CORBA), a standard defined by the Object Management Group, and the Message Passing Interface (MPI), a standard developed by a group of researchers from academia and industry. Both have well-tested and efficient implementations, including some that are freely available under the GNU public licenses. The CORBA component enables individual programs written in different languages and running on different platforms within a network to exchange data with each other, thus behaving like a single application. MPI provides the process-to-process intercommunication between these programs. This paper outlines the different CORBA and

Exact Solutions for Internuclear Vectors and Backbone Dihedral Angles from NH Residual Dipolar Couplings in Two Media, and their Application in a Systematic Search Algorithm for Determining Protein Backbone Structure

International Nuclear Information System (INIS)

Wang Lincong; Donald, Bruce Randall

2004-01-01

We have derived a quartic equation for computing the direction of an internuclear vector from residual dipolar couplings (RDCs) measured in two aligning media, and two simple trigonometric equations for computing the backbone (φ,ψ) angles from two backbone vectors in consecutive peptide planes. These equations make it possible to compute, exactly and in constant time, the backbone (φ,ψ) angles for a residue from RDCs in two media on any single backbone vector type. Building upon these exact solutions we have designed a novel algorithm for determining a protein backbone substructure consisting of α-helices and β-sheets. Our algorithm employs a systematic search technique to refine the conformation of both α-helices and β-sheets and to determine their orientations using exclusively the angular restraints from RDCs. The algorithm computes the backbone substructure employing very sparse distance restraints between pairs of α-helices and β-sheets refined by the systematic search. The algorithm has been demonstrated on the protein human ubiquitin using only backbone NH RDCs, plus twelve hydrogen bonds and four NOE distance restraints. Further, our results show that both the global orientations and the conformations of α-helices and β-strands can be determined with high accuracy using only two RDCs per residue. The algorithm requires, as its input, backbone resonance assignments, the identification of α-helices and β-sheets as well as sparse NOE distance and hydrogen bond restraints.Abbreviations: NMR - nuclear magnetic resonance; RDC - residual dipolar coupling; NOE - nuclear Overhauser effect; SVD - singular value decomposition; DFS - depth-first search; RMSD - root mean square deviation; POF - principal order frame; PDB - protein data bank; SA - simulated annealing; MD - molecular dynamics

Solution NMR Structures of Oxidized and Reduced Ehrlichia chaffeensis thioredoxin: NMR-Invisible Structure Owing to Backbone Dynamics

Energy Technology Data Exchange (ETDEWEB)

Buchko, Garry W.; Hewitt, Stephen N.; Van Voorhis, Wesley C.; Myler, Peter J.

2018-01-02

Thioredoxins (Trxs) are small ubiquitous proteins that participate in a diverse variety of redox reactions via the reversible oxidation of two cysteine thiol groups in a structurally conserved active site, CGPC. Here, we describe the NMR solution structures of a Trx from Ehrlichia chaffeensis (Ec-Trx, ECH_0218), the etiological agent responsible for human monocytic ehrlichiosis, in both the oxidized and reduced states. The overall topology of the calculated structures is similar in both redox states and similar to other Trx structures, a five-strand, mixed -sheet (1:3:2:4:5) surrounded by four -helices. Unlike other Trxs studied by NMR in both redox states, the 1H-15N HSQC spectra of reduced Ec-Trx was missing eight amide cross peaks relative to the spectra of oxidized Ec-Trx. These missing amides correspond to residues C32-E39 in the active site containing helix (2) and S72-I75 in a loop near the active site and suggest a substantial change in the backbone dynamics associated with the formation of an intramolecular C32-C35 disulfide bond.

(nBuCp)2ZrCl2-catalyzed Ethylene-4M1P Copolymerization: Copolymer Backbone Structure, Melt Behavior, and Crystallization

KAUST Repository

Atiqullah, Muhammad; Adamu, Sagir; Malaibari, Zuhair O.; Al-Harthi, Mamdouh A.; Emwas, Abdul-Hamid M.

2016-01-01

The judicious design of methylaluminoxane (MAO) anions expands the scope for developing industrial metallocene catalysts. Therefore, the effects of MAO anion design on the backbone structure, melt behavior, and crystallization of ethylene−4-methyl-1

ExScal Backbone Network Architecture

Science.gov (United States)

2005-01-01

802.11 battery powered nodes was laid over the sensor network. We adopted the Stargate platform for the backbone tier to serve as the basis for...its head. XSS Hardware and Network: XSS stands for eXtreme Scaling Stargate . A stargate is a linux-based single board computer. It has a 400 MHz

Backbone Diversity Analysis in Catalyst Design

NARCIS (Netherlands)

Maldonado, A.G.; Hageman, J.A.; Mastroianni, S.; Rothenberg, G.

2009-01-01

We present a computer-based heuristic framework for designing libraries of homogeneous catalysts. In this approach, a set of given bidentate ligand-metal complexes is disassembled into key substructures (building blocks). These include metal atoms, ligating groups, backbone groups, and residue

Routing protocol for wireless quantum multi-hop mesh backbone network based on partially entangled GHZ state

Science.gov (United States)

Xiong, Pei-Ying; Yu, Xu-Tao; Zhang, Zai-Chen; Zhan, Hai-Tao; Hua, Jing-Yu

2017-08-01

Quantum multi-hop teleportation is important in the field of quantum communication. In this study, we propose a quantum multi-hop communication model and a quantum routing protocol with multihop teleportation for wireless mesh backbone networks. Based on an analysis of quantum multi-hop protocols, a partially entangled Greenberger-Horne-Zeilinger (GHZ) state is selected as the quantum channel for the proposed protocol. Both quantum and classical wireless channels exist between two neighboring nodes along the route. With the proposed routing protocol, quantum information can be transmitted hop by hop from the source node to the destination node. Based on multi-hop teleportation based on the partially entangled GHZ state, a quantum route established with the minimum number of hops. The difference between our routing protocol and the classical one is that in the former, the processes used to find a quantum route and establish quantum channel entanglement occur simultaneously. The Bell state measurement results of each hop are piggybacked to quantum route finding information. This method reduces the total number of packets and the magnitude of air interface delay. The deduction of the establishment of a quantum channel between source and destination is also presented here. The final success probability of quantum multi-hop teleportation in wireless mesh backbone networks was simulated and analyzed. Our research shows that quantum multi-hop teleportation in wireless mesh backbone networks through a partially entangled GHZ state is feasible.

Charge transport properties of poly(dA)-poly(dT) DNA in variation of backbone disorder and amplitude of base-pair twisting motion

Energy Technology Data Exchange (ETDEWEB)

Rahmi, Kinanti Aldilla, E-mail: kinanti.aldilla@ui.ac.id; Yudiarsah, Efta [Physics Department, FMIPA, Universitas Indonesia, Kampus UI Depok (Indonesia)

2016-04-19

By using tight binding Hamiltonian model, charge transport properties of poly(dA)-poly(dT) DNA in variation of backbone disorder and amplitude of base-pair twisting motion is studied. The DNA chain used is 32 base pairs long poly(dA)-poly(dT) molecule. The molecule is contacted to electrode at both ends. The influence of environment on charge transport in DNA is modeled as variation of backbone disorder. The twisting motion amplitude is taking into account by assuming that the twisting angle distributes following Gaussian distribution function with zero average and standard deviation proportional to square root of temperature and inversely proportional to the twisting motion frequency. The base-pair twisting motion influences both the onsite energy of the bases and electron hopping constant between bases. The charge transport properties are studied by calculating current using Landauer-Buttiker formula from transmission probabilities which is calculated by transfer matrix methods. The result shows that as the backbone disorder increases, the maximum current decreases. By decreasing the twisting motion frequency, the current increases rapidly at low voltage, but the current increases slower at higher voltage. The threshold voltage can increase or decrease with increasing backbone disorder and increasing twisting frequency.

40-Gbps optical backbone network deep packet inspection based on FPGA

Science.gov (United States)

Zuo, Yuan; Huang, Zhiping; Su, Shaojing

2014-11-01

In the era of information, the big data, which contains huge information, brings about some problems, such as high speed transmission, storage and real-time analysis and process. As the important media for data transmission, the Internet is the significant part for big data processing research. With the large-scale usage of the Internet, the data streaming of network is increasing rapidly. The speed level in the main fiber optic communication of the present has reached 40Gbps, even 100Gbps, therefore data on the optical backbone network shows some features of massive data. Generally, data services are provided via IP packets on the optical backbone network, which is constituted with SDH (Synchronous Digital Hierarchy). Hence this method that IP packets are directly mapped into SDH payload is named POS (Packet over SDH) technology. Aiming at the problems of real time process of high speed massive data, this paper designs a process system platform based on ATCA for 40Gbps POS signal data stream recognition and packet content capture, which employs the FPGA as the CPU. This platform offers pre-processing of clustering algorithms, service traffic identification and data mining for the following big data storage and analysis with high efficiency. Also, the operational procedure is proposed in this paper. Four channels of 10Gbps POS signal decomposed by the analysis module, which chooses FPGA as the kernel, are inputted to the flow classification module and the pattern matching component based on TCAM. Based on the properties of the length of payload and net flows, buffer management is added to the platform to keep the key flow information. According to data stream analysis, DPI (deep packet inspection) and flow balance distribute, the signal is transmitted to the backend machine through the giga Ethernet ports on back board. Practice shows that the proposed platform is superior to the traditional applications based on ASIC and NP.

Annotating the protein-RNA interaction sites in proteins using evolutionary information and protein backbone structure.

Science.gov (United States)

Li, Tao; Li, Qian-Zhong

2012-11-07

RNA-protein interactions play important roles in various biological processes. The precise detection of RNA-protein interaction sites is very important for understanding essential biological processes and annotating the function of the proteins. In this study, based on various features from amino acid sequence and structure, including evolutionary information, solvent accessible surface area and torsion angles (φ, ψ) in the backbone structure of the polypeptide chain, a computational method for predicting RNA-binding sites in proteins is proposed. When the method is applied to predict RNA-binding sites in three datasets: RBP86 containing 86 protein chains, RBP107 containing 107 proteins chains and RBP109 containing 109 proteins chains, better sensitivities and specificities are obtained compared to previously published methods in five-fold cross-validation tests. In order to make further examination for the efficiency of our method, the RBP107 dataset is used as training set, RBP86 and RBP109 datasets are used as the independent test sets. In addition, as examples of our prediction, RNA-binding sites in a few proteins are presented. The annotated results are consistent with the PDB annotation. These results show that our method is useful for annotating RNA binding sites of novel proteins.

Study of muscular skeletal apparatus’s functional state of junior sportsmen-power lifters, who have backbone verterbral abnormalities

Directory of Open Access Journals (Sweden)

V.R. Ilmatov

2015-10-01

Full Text Available Purpose: determination of abnormalities and disorders of muscular skeletal apparatuses’ status of power lifters, who have vertebral abnormalities of backbone. Material: 58 junior sportsmen participated in the research. 36 sportsmen were the main group of the research and had vertebral disorders in backbone. For posture testing visual examination was used. Backbone mobility was tested with goniometry method. Flat feet were registered with plantography method. Results: we determined posture abnormalities in sagittal and frontal planes; feet flat, limited maximal movements in thoracic and lumbar spines. It was determined that the most limited were rotational movements and backbone unbending. The next were side bents. These limitations were accompanied by pain syndrome. These observations indirectly confirmed theory of direct interaction of backbone structures with nervous structures. It is also a confirmation of vertebral abnormalities’ presence in junior sportsmen. Conclusions: it was found that in junior sportsmen - power lifters with backbone pathologies in 100% of cases symptoms are determined by local limitations of backbone mobility with pain syndrome. In 35% of cases they are accompanied by posture’s disorders and feet flat. Orientation and methodic of rehabilitation of such sportsmen have been determined.

Backbone structure of Yersinia pestis Ail determined in micelles by NMR-restrained simulated annealing with implicit membrane solvation

International Nuclear Information System (INIS)

Marassi, Francesca M.; Ding, Yi; Schwieters, Charles D.; Tian, Ye; Yao, Yong

2015-01-01

The outer membrane protein Ail (attachment invasion locus) is a virulence factor of Yersinia pestis that mediates cell invasion, cell attachment and complement resistance. Here we describe its three-dimensional backbone structure determined in decyl-phosphocholine (DePC) micelles by NMR spectroscopy. The NMR structure was calculated using the membrane function of the implicit solvation potential, eefxPot, which we have developed to facilitate NMR structure calculations in a physically realistic environment. We show that the eefxPot force field guides the protein towards its native fold. The resulting structures provide information about the membrane-embedded global position of Ail, and have higher accuracy, higher precision and improved conformational properties, compared to the structures calculated with the standard repulsive potential

Peptoid-Peptide hybrid backbone architectures

DEFF Research Database (Denmark)

Olsen, Christian Adam

2010-01-01

Peptidomimetic oligomers and foldamers have received considerable attention for over a decade, with beta-peptides and the so-called peptoids (N-alkylglycine oligomers) representing prominent examples of such architectures. Lately, hybrid or mixed backbones consisting of both alpha- and beta......-amino acids (alpha/beta-peptides) have been investigated in some detail as well. The present Minireview is a survey of the literature concerning hybrid structures of alpha-amino acids and peptoids, including beta-peptoids (N-alkyl-beta-alanine oligomers), and is intended to give an overview of this area...

Backbone upgrades and DEC equipment replacement

Science.gov (United States)

Vancamp, Warren

1991-01-01

The NASA Science Internet (NSI) dual protocol backbone is outlined. It includes DECnet link upgrades to match TCP/IP link performance. It also includes the integration of backbone resources and central management. The phase 1 transition process is outlined.

Controlled Conjugated Backbone Twisting for an Increased Open-Circuit Voltage while Having a High Short-Circuit Current in Poly(hexylthiophene) Derivatives

KAUST Repository

Ko, Sangwon

2012-03-21

Conjugated polymers with nearly planar backbones have been the most commonly investigated materials for organic-based electronic devices. More twisted polymer backbones have been shown to achieve larger open-circuit voltages in solar cells, though with decreased short-circuit current densities. We systematically impose twists within a family of poly(hexylthiophene)s and examine their influence on the performance of polymer:fullerene bulk heterojunction (BHJ) solar cells. A simple chemical modification concerning the number and placement of alkyl side chains along the conjugated backbone is used to control the degree of backbone twisting. Density functional theory calculations were carried out on a series of oligothiophene structures to provide insights on how the sterically induced twisting influences the geometric, electronic, and optical properties. Grazing incidence X-ray scattering measurements were performed to investigate how the thin-film packing structure was affected. The open-circuit voltage and charge-transfer state energy of the polymer:fullerene BHJ solar cells increased substantially with the degree of twist induced within the conjugated backbone-due to an increase in the polymer ionization potential-while the short-circuit current decreased as a result of a larger optical gap and lower hole mobility. A controlled, moderate degree of twist along the poly(3,4-dihexyl-2,2′:5′,2′′- terthiophene) (PDHTT) conjugated backbone led to a 19% enhancement in the open-circuit voltage (0.735 V) vs poly(3-hexylthiophene)-based devices, while similar short-circuit current densities, fill factors, and hole-carrier mobilities were maintained. These factors resulted in a power conversion efficiency of 4.2% for a PDHTT:[6,6]-phenyl-C 71-butyric acid methyl ester (PC 71BM) blend solar cell without thermal annealing. This simple approach reveals a molecular design avenue to increase open-circuit voltage while retaining the short-circuit current. © 2012 American

Controlled conjugated backbone twisting for an increased open-circuit voltage while having a high short-circuit current in poly(hexylthiophene) derivatives.

Science.gov (United States)

Ko, Sangwon; Hoke, Eric T; Pandey, Laxman; Hong, Sanghyun; Mondal, Rajib; Risko, Chad; Yi, Yuanping; Noriega, Rodrigo; McGehee, Michael D; Brédas, Jean-Luc; Salleo, Alberto; Bao, Zhenan

2012-03-21

Conjugated polymers with nearly planar backbones have been the most commonly investigated materials for organic-based electronic devices. More twisted polymer backbones have been shown to achieve larger open-circuit voltages in solar cells, though with decreased short-circuit current densities. We systematically impose twists within a family of poly(hexylthiophene)s and examine their influence on the performance of polymer:fullerene bulk heterojunction (BHJ) solar cells. A simple chemical modification concerning the number and placement of alkyl side chains along the conjugated backbone is used to control the degree of backbone twisting. Density functional theory calculations were carried out on a series of oligothiophene structures to provide insights on how the sterically induced twisting influences the geometric, electronic, and optical properties. Grazing incidence X-ray scattering measurements were performed to investigate how the thin-film packing structure was affected. The open-circuit voltage and charge-transfer state energy of the polymer:fullerene BHJ solar cells increased substantially with the degree of twist induced within the conjugated backbone--due to an increase in the polymer ionization potential--while the short-circuit current decreased as a result of a larger optical gap and lower hole mobility. A controlled, moderate degree of twist along the poly(3,4-dihexyl-2,2':5',2''-terthiophene) (PDHTT) conjugated backbone led to a 19% enhancement in the open-circuit voltage (0.735 V) vs poly(3-hexylthiophene)-based devices, while similar short-circuit current densities, fill factors, and hole-carrier mobilities were maintained. These factors resulted in a power conversion efficiency of 4.2% for a PDHTT:[6,6]-phenyl-C(71)-butyric acid methyl ester (PC(71)BM) blend solar cell without thermal annealing. This simple approach reveals a molecular design avenue to increase open-circuit voltage while retaining the short-circuit current.

CSSI-PRO: a method for secondary structure type editing, assignment and estimation in proteins using linear combination of backbone chemical shifts

International Nuclear Information System (INIS)

Swain, Monalisa; Atreya, Hanudatta S.

2009-01-01

Estimation of secondary structure in polypeptides is important for studying their structure, folding and dynamics. In NMR spectroscopy, such information is generally obtained after sequence specific resonance assignments are completed. We present here a new methodology for assignment of secondary structure type to spin systems in proteins directly from NMR spectra, without prior knowledge of resonance assignments. The methodology, named Combination of Shifts for Secondary Structure Identification in Proteins (CSSI-PRO), involves detection of specific linear combination of backbone 1 H α and 13 C' chemical shifts in a two-dimensional (2D) NMR experiment based on G-matrix Fourier transform (GFT) NMR spectroscopy. Such linear combinations of shifts facilitate editing of residues belonging to α-helical/β-strand regions into distinct spectral regions nearly independent of the amino acid type, thereby allowing the estimation of overall secondary structure content of the protein. Comparison of the predicted secondary structure content with those estimated based on their respective 3D structures and/or the method of Chemical Shift Index for 237 proteins gives a correlation of more than 90% and an overall rmsd of 7.0%, which is comparable to other biophysical techniques used for structural characterization of proteins. Taken together, this methodology has a wide range of applications in NMR spectroscopy such as rapid protein structure determination, monitoring conformational changes in protein-folding/ligand-binding studies and automated resonance assignment

Predicting backbone Cα angles and dihedrals from protein sequences by stacked sparse auto-encoder deep neural network.

Science.gov (United States)

Lyons, James; Dehzangi, Abdollah; Heffernan, Rhys; Sharma, Alok; Paliwal, Kuldip; Sattar, Abdul; Zhou, Yaoqi; Yang, Yuedong

2014-10-30

Because a nearly constant distance between two neighbouring Cα atoms, local backbone structure of proteins can be represented accurately by the angle between C(αi-1)-C(αi)-C(αi+1) (θ) and a dihedral angle rotated about the C(αi)-C(αi+1) bond (τ). θ and τ angles, as the representative of structural properties of three to four amino-acid residues, offer a description of backbone conformations that is complementary to φ and ψ angles (single residue) and secondary structures (>3 residues). Here, we report the first machine-learning technique for sequence-based prediction of θ and τ angles. Predicted angles based on an independent test have a mean absolute error of 9° for θ and 34° for τ with a distribution on the θ-τ plane close to that of native values. The average root-mean-square distance of 10-residue fragment structures constructed from predicted θ and τ angles is only 1.9Å from their corresponding native structures. Predicted θ and τ angles are expected to be complementary to predicted ϕ and ψ angles and secondary structures for using in model validation and template-based as well as template-free structure prediction. The deep neural network learning technique is available as an on-line server called Structural Property prediction with Integrated DEep neuRal network (SPIDER) at http://sparks-lab.org. Copyright © 2014 Wiley Periodicals, Inc.

The extension of a DNA double helix by an additional Watson-Crick base pair on the same backbone.

Science.gov (United States)

Kumar, Pawan; Sharma, Pawan K; Madsen, Charlotte S; Petersen, Michael; Nielsen, Poul

2013-06-17

Additional base pair: The DNA duplex can be extended with an additional Watson-Crick base pair on the same backbone by the use of double-headed nucleotides. These also work as compressed dinucleotides and form two base pairs with cognate nucleobases on the opposite strand. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Five Principles of Industrialized Transformation for Successfully Building an Operational Backbone

DEFF Research Database (Denmark)

Winkler, Till J.; Kettunen, Petteri

2018-01-01

approach that is underpinned by five principles—template-based, business-driven, matrix-organized, tight supplier steering and cascaded planning. The UPM case provides important lessons for transformation leaders seeking to build, expand or develop a value-adding operational backbone.......To move into the digital age, a globally operating company needs to have in place an operational backbone, but many struggle with achieving this and the associated transformation program. Based on the experience of UPM, a Finnish forest industry company, we describe an industrialized transformation...

Some fractal properties of the percolating backbone in two dimensions

International Nuclear Information System (INIS)

Laidlaw, D.; MacKay, G.; Jan, N.

1987-01-01

A new algorithm is presented, based on elements of artificial intelligence theory, to determine the fractal properties of the backbone of the incipient infinite cluster. It is found that fractal dimensionality of the backbone is d/sub f//sup BB/ = 1.61 +/- 0.01, the chemical dimensionality is d/sub t/ = 1.40 +/- 0.01, and the fractal dimension of the minimum path d/sub min/ = 1.15 +/- 0.02 for the two-dimensional triangular lattice

TRX-LOGOS - a graphical tool to demonstrate DNA information content dependent upon backbone dynamics in addition to base sequence.

Science.gov (United States)

Fortin, Connor H; Schulze, Katharina V; Babbitt, Gregory A

2015-01-01

It is now widely-accepted that DNA sequences defining DNA-protein interactions functionally depend upon local biophysical features of DNA backbone that are important in defining sites of binding interaction in the genome (e.g. DNA shape, charge and intrinsic dynamics). However, these physical features of DNA polymer are not directly apparent when analyzing and viewing Shannon information content calculated at single nucleobases in a traditional sequence logo plot. Thus, sequence logos plots are severely limited in that they convey no explicit information regarding the structural dynamics of DNA backbone, a feature often critical to binding specificity. We present TRX-LOGOS, an R software package and Perl wrapper code that interfaces the JASPAR database for computational regulatory genomics. TRX-LOGOS extends the traditional sequence logo plot to include Shannon information content calculated with regard to the dinucleotide-based BI-BII conformation shifts in phosphate linkages on the DNA backbone, thereby adding a visual measure of intrinsic DNA flexibility that can be critical for many DNA-protein interactions. TRX-LOGOS is available as an R graphics module offered at both SourceForge and as a download supplement at this journal. To demonstrate the general utility of TRX logo plots, we first calculated the information content for 416 Saccharomyces cerevisiae transcription factor binding sites functionally confirmed in the Yeastract database and matched to previously published yeast genomic alignments. We discovered that flanking regions contain significantly elevated information content at phosphate linkages than can be observed at nucleobases. We also examined broader transcription factor classifications defined by the JASPAR database, and discovered that many general signatures of transcription factor binding are locally more information rich at the level of DNA backbone dynamics than nucleobase sequence. We used TRX-logos in combination with MEGA 6.0 software

Porous solid backbone impregnation for electrochemical energy conversion systems

KAUST Repository

Boulfrad, Samir; Jabbour, Ghassan

2013-01-01

An apparatus and method for impregnating a porous solid backbone. The apparatus may include a platform for holding a porous solid backbone, an ink jet nozzle configured to dispense a liquid solution onto the porous solid backbone, a positioning mechanism configured to position the ink jet nozzle proximate to a plurality of locations of the porous solid backbone, and a control unit configured to control the positioning mechanism to position the ink jet nozzle proximate to the plurality of locations and cause the ink jet nozzle to dispense the liquid solution onto the porous solid backbone.

Porous solid backbone impregnation for electrochemical energy conversion systems

KAUST Repository

Boulfrad, Samir

2013-09-19

An apparatus and method for impregnating a porous solid backbone. The apparatus may include a platform for holding a porous solid backbone, an ink jet nozzle configured to dispense a liquid solution onto the porous solid backbone, a positioning mechanism configured to position the ink jet nozzle proximate to a plurality of locations of the porous solid backbone, and a control unit configured to control the positioning mechanism to position the ink jet nozzle proximate to the plurality of locations and cause the ink jet nozzle to dispense the liquid solution onto the porous solid backbone.

An efficient randomized algorithm for contact-based NMR backbone resonance assignment.

Science.gov (United States)

Kamisetty, Hetunandan; Bailey-Kellogg, Chris; Pandurangan, Gopal

2006-01-15

Backbone resonance assignment is a critical bottleneck in studies of protein structure, dynamics and interactions by nuclear magnetic resonance (NMR) spectroscopy. A minimalist approach to assignment, which we call 'contact-based', seeks to dramatically reduce experimental time and expense by replacing the standard suite of through-bond experiments with the through-space (nuclear Overhauser enhancement spectroscopy, NOESY) experiment. In the contact-based approach, spectral data are represented in a graph with vertices for putative residues (of unknown relation to the primary sequence) and edges for hypothesized NOESY interactions, such that observed spectral peaks could be explained if the residues were 'close enough'. Due to experimental ambiguity, several incorrect edges can be hypothesized for each spectral peak. An assignment is derived by identifying consistent patterns of edges (e.g. for alpha-helices and beta-sheets) within a graph and by mapping the vertices to the primary sequence. The key algorithmic challenge is to be able to uncover these patterns even when they are obscured by significant noise. This paper develops, analyzes and applies a novel algorithm for the identification of polytopes representing consistent patterns of edges in a corrupted NOESY graph. Our randomized algorithm aggregates simplices into polytopes and fixes inconsistencies with simple local modifications, called rotations, that maintain most of the structure already uncovered. In characterizing the effects of experimental noise, we employ an NMR-specific random graph model in proving that our algorithm gives optimal performance in expected polynomial time, even when the input graph is significantly corrupted. We confirm this analysis in simulation studies with graphs corrupted by up to 500% noise. Finally, we demonstrate the practical application of the algorithm on several experimental beta-sheet datasets. Our approach is able to eliminate a large majority of noise edges and to

Structural conservation, variability, and immunogenicity of the T6 backbone pilin of serotype M6 Streptococcus pyogenes.

Science.gov (United States)

Young, Paul G; Moreland, Nicole J; Loh, Jacelyn M; Bell, Anita; Atatoa Carr, Polly; Proft, Thomas; Baker, Edward N

2014-07-01

Group A streptococcus (GAS; Streptococcus pyogenes) is a Gram-positive human pathogen that causes a broad range of diseases ranging from acute pharyngitis to the poststreptococcal sequelae of acute rheumatic fever. GAS pili are highly diverse, long protein polymers that extend from the cell surface. They have multiple roles in infection and are promising candidates for vaccine development. This study describes the structure of the T6 backbone pilin (BP; Lancefield T-antigen) from the important M6 serotype. The structure reveals a modular arrangement of three tandem immunoglobulin-like domains, two with internal isopeptide bonds. The T6 pilin lysine, essential for polymerization, is located in a novel VAKS motif that is structurally homologous to the canonical YPKN pilin lysine in other three- and four-domain Gram-positive pilins. The T6 structure also highlights a conserved pilin core whose surface is decorated with highly variable loops and extensions. Comparison to other Gram-positive BPs shows that many of the largest variable extensions are found in conserved locations. Studies with sera from patients diagnosed with GAS-associated acute rheumatic fever showed that each of the three T6 domains, and the largest of the variable extensions (V8), are targeted by IgG during infection in vivo. Although the GAS BP show large variations in size and sequence, the modular nature of the pilus proteins revealed by the T6 structure may aid the future design of a pilus-based vaccine. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Backbone dynamics of the EIAV-Tat protein from 15N relaxation studies

International Nuclear Information System (INIS)

Ejchart, A.; Herrmann, F.; Roesch, P.; Sticht, H.; Willbold, D.

1994-01-01

The work investigates the mobility of EIAV-Tat protein backbone by measuring the relaxation parameters of the 15 N nitrogens. High degree of the flexibility, non-typical of rigid, well structured proteins was shown

Lactobacillus plantarum possesses the capability for wall teichoic acid backbone alditol switching

Directory of Open Access Journals (Sweden)

Bron Peter A

2012-09-01

Full Text Available Abstract Background Specific strains of Lactobacillus plantarum are marketed as health-promoting probiotics. The role and interplay of cell-wall compounds like wall- and lipo-teichoic acids (WTA and LTA in bacterial physiology and probiotic-host interactions remain obscure. L. plantarum WCFS1 harbors the genetic potential to switch WTA backbone alditol, providing an opportunity to study the impact of WTA backbone modifications in an isogenic background. Results Through genome mining and mutagenesis we constructed derivatives that synthesize alternative WTA variants. The mutants were shown to completely lack WTA, or produce WTA and LTA that lack D-Ala substitution, or ribitol-backbone WTA instead of the wild-type glycerol-containing backbone. DNA micro-array experiments established that the tarIJKL gene cluster is required for the biosynthesis of this alternative WTA backbone, and suggest ribose and arabinose are precursors thereof. Increased tarIJKL expression was not observed in any of our previously performed DNA microarray experiments, nor in qRT-PCR analyses of L. plantarum grown on various carbon sources, leaving the natural conditions leading to WTA backbone alditol switching, if any, to be identified. Human embryonic kidney NF-κB reporter cells expressing Toll like receptor (TLR-2/6 were exposed to purified WTAs and/or the TA mutants, indicating that WTA is not directly involved in TLR-2/6 signaling, but attenuates this signaling in a backbone independent manner, likely by affecting the release and exposure of immunomodulatory compounds such as LTA. Moreover, human dendritic cells did not secrete any cytokines when purified WTAs were applied, whereas they secreted drastically decreased levels of the pro-inflammatory cytokines IL-12p70 and TNF-α after stimulation with the WTA mutants as compared to the wild-type. Conclusions The study presented here correlates structural differences in WTA to their functional characteristics, thereby

On the relationship between NMR-derived amide order parameters and protein backbone entropy changes.

Science.gov (United States)

Sharp, Kim A; O'Brien, Evan; Kasinath, Vignesh; Wand, A Joshua

2015-05-01

Molecular dynamics simulations are used to analyze the relationship between NMR-derived squared generalized order parameters of amide NH groups and backbone entropy. Amide order parameters (O(2) NH ) are largely determined by the secondary structure and average values appear unrelated to the overall flexibility of the protein. However, analysis of the more flexible subset (O(2) NH  entropy than that reported by the side chain methyl axis order parameters, O(2) axis . A calibration curve for backbone entropy vs. O(2) NH is developed, which accounts for both correlations between amide group motions of different residues, and correlations between backbone and side chain motions. This calibration curve can be used with experimental values of O(2) NH changes obtained by NMR relaxation measurements to extract backbone entropy changes, for example, upon ligand binding. In conjunction with our previous calibration for side chain entropy derived from measured O(2) axis values this provides a prescription for determination of the total protein conformational entropy changes from NMR relaxation measurements. © 2015 Wiley Periodicals, Inc.

Free vibration analysis of a robotic fish based on a continuous and non-uniform flexible backbone with distributed masses

Science.gov (United States)

Coral, W.; Rossi, C.; Curet, O. M.

2015-12-01

This paper presents a Differential Quadrature Element Method for free transverse vibration of a robotic fish based on a continuous and non-uniform flexible backbone with distributed masses (fish ribs). The proposed method is based on the theory of a Timoshenko cantilever beam. The effects of the masses (number, magnitude and position) on the value of natural frequencies are investigated. Governing equations, compatibility and boundary conditions are formulated according to the Differential Quadrature rules. The convergence, efficiency and accuracy are compared to other analytical solution proposed in the literature. Moreover, the proposed method has been validate against the physical prototype of a flexible fish backbone. The main advantages of this method, compared to the exact solutions available in the literature are twofold: first, smaller computational cost and second, it allows analysing the free vibration in beams whose section is an arbitrary function, which is normally difficult or even impossible with other analytical methods.

Backbone Brackets and Arginine Tweezers delineate Class I and Class II aminoacyl tRNA synthetases

Science.gov (United States)

Haupt, V. Joachim; Schroeder, Michael; Labudde, Dirk

2018-01-01

The origin of the machinery that realizes protein biosynthesis in all organisms is still unclear. One key component of this machinery are aminoacyl tRNA synthetases (aaRS), which ligate tRNAs to amino acids while consuming ATP. Sequence analyses revealed that these enzymes can be divided into two complementary classes. Both classes differ significantly on a sequence and structural level, feature different reaction mechanisms, and occur in diverse oligomerization states. The one unifying aspect of both classes is their function of binding ATP. We identified Backbone Brackets and Arginine Tweezers as most compact ATP binding motifs characteristic for each Class. Geometric analysis shows a structural rearrangement of the Backbone Brackets upon ATP binding, indicating a general mechanism of all Class I structures. Regarding the origin of aaRS, the Rodin-Ohno hypothesis states that the peculiar nature of the two aaRS classes is the result of their primordial forms, called Protozymes, being encoded on opposite strands of the same gene. Backbone Brackets and Arginine Tweezers were traced back to the proposed Protozymes and their more efficient successors, the Urzymes. Both structural motifs can be observed as pairs of residues in contemporary structures and it seems that the time of their addition, indicated by their placement in the ancient aaRS, coincides with the evolutionary trace of Proto- and Urzymes. PMID:29659563

Radiation safety system (RSS) backbones: Design, engineering, fabrication and installation

International Nuclear Information System (INIS)

Wilmarth, J.E.; Sturrock, J.C.; Gallegos, F.R.

1998-01-01

The Radiation Safety System (RSS) Backbones are part of an electrical/electronic/mechanical system insuring safe access and exclusion of personnel to areas at the Los Alamos Neutron Science Center (LANSCE) accelerator. The RSS Backbones control the safety fusible beam plugs which terminate transmission of accelerated ion beams in response to predefined conditions. Any beam or access fault of the backbone inputs will cause insertion of the beam plugs in the low energy beam transport. The Backbones serve the function of tying the beam plugs to the access control systems, beam spill monitoring systems and current-level limiting systems. In some ways the Backbones may be thought of as a spinal column with beam plugs at the head and nerve centers along the spinal column. The two Linac Backbone segments and experimental area segments form a continuous cable plant over 3,500 feet from beam plugs to the tip on the longest tail. The Backbones were installed in compliance with current safety standards, such as installation of the two segments in separate conduits or tray. Monitoring for ground-faults and input wiring verification was an added enhancement to the system. The system has the capability to be tested remotely

Protein structure refinement using a quantum mechanics-based chemical shielding predictor

DEFF Research Database (Denmark)

Bratholm, Lars Andersen; Jensen, Jan Halborg

2017-01-01

The accurate prediction of protein chemical shifts using a quantum mechanics (QM)-based method has been the subject of intense research for more than 20 years but so far empirical methods for chemical shift prediction have proven more accurate. In this paper we show that a QM-based predictor...... of a protein backbone and CB chemical shifts (ProCS15, PeerJ, 2016, 3, e1344) is of comparable accuracy to empirical chemical shift predictors after chemical shift-based structural refinement that removes small structural errors. We present a method by which quantum chemistry based predictions of isotropic...

AbDesign: An algorithm for combinatorial backbone design guided by natural conformations and sequences.

Science.gov (United States)

Lapidoth, Gideon D; Baran, Dror; Pszolla, Gabriele M; Norn, Christoffer; Alon, Assaf; Tyka, Michael D; Fleishman, Sarel J

2015-08-01

Computational design of protein function has made substantial progress, generating new enzymes, binders, inhibitors, and nanomaterials not previously seen in nature. However, the ability to design new protein backbones for function--essential to exert control over all polypeptide degrees of freedom--remains a critical challenge. Most previous attempts to design new backbones computed the mainchain from scratch. Here, instead, we describe a combinatorial backbone and sequence optimization algorithm called AbDesign, which leverages the large number of sequences and experimentally determined molecular structures of antibodies to construct new antibody models, dock them against target surfaces and optimize their sequence and backbone conformation for high stability and binding affinity. We used the algorithm to produce antibody designs that target the same molecular surfaces as nine natural, high-affinity antibodies; in five cases interface sequence identity is above 30%, and in four of those the backbone conformation at the core of the antibody binding surface is within 1 Å root-mean square deviation from the natural antibodies. Designs recapitulate polar interaction networks observed in natural complexes, and amino acid sidechain rigidity at the designed binding surface, which is likely important for affinity and specificity, is high compared to previous design studies. In designed anti-lysozyme antibodies, complementarity-determining regions (CDRs) at the periphery of the interface, such as L1 and H2, show greater backbone conformation diversity than the CDRs at the core of the interface, and increase the binding surface area compared to the natural antibody, potentially enhancing affinity and specificity. © 2015 Wiley Periodicals, Inc.

Marburg virus VP35 can both fully coat the backbone and cap the ends of dsRNA for interferon antagonism.

Directory of Open Access Journals (Sweden)

Shridhar Bale

2012-09-01

Full Text Available Filoviruses, including Marburg virus (MARV and Ebola virus (EBOV, cause fatal hemorrhagic fever in humans and non-human primates. All filoviruses encode a unique multi-functional protein termed VP35. The C-terminal double-stranded (dsRNA-binding domain (RBD of VP35 has been implicated in interferon antagonism and immune evasion. Crystal structures of the VP35 RBD from two ebolaviruses have previously demonstrated that the viral protein caps the ends of dsRNA. However, it is not yet understood how the expanses of dsRNA backbone, between the ends, are masked from immune surveillance during filovirus infection. Here, we report the crystal structure of MARV VP35 RBD bound to dsRNA. In the crystal structure, molecules of dsRNA stack end-to-end to form a pseudo-continuous oligonucleotide. This oligonucleotide is continuously and completely coated along its sugar-phosphate backbone by the MARV VP35 RBD. Analysis of dsRNA binding by dot-blot and isothermal titration calorimetry reveals that multiple copies of MARV VP35 RBD can indeed bind the dsRNA sugar-phosphate backbone in a cooperative manner in solution. Further, MARV VP35 RBD can also cap the ends of the dsRNA in solution, although this arrangement was not captured in crystals. Together, these studies suggest that MARV VP35 can both coat the backbone and cap the ends, and that for MARV, coating of the dsRNA backbone may be an essential mechanism by which dsRNA is masked from backbone-sensing immune surveillance molecules.

Constructing Battery-Aware Virtual Backbones in Wireless Sensor Networks

Directory of Open Access Journals (Sweden)

Yang Yuanyuan

2007-01-01

Full Text Available A critical issue in battery-powered sensor networks is to construct energy efficient virtual backbones for network routing. Recent study in battery technology reveals that batteries tend to discharge more power than needed and reimburse the over-discharged power if they are recovered. In this paper we first provide a mathematical battery model suitable for implementation in sensor networks. We then introduce the concept of battery-aware connected dominating set (BACDS and show that in general the minimum BACDS (MBACDS can achieve longer lifetime than the previous backbone structures. Then we show that finding a MBACDS is NP-hard and give a distributed approximation algorithm to construct the BACDS. The resulting BACDS constructed by our algorithm is at most opt size, where is the maximum node degree and opt is the size of an optimal BACDS. Simulation results show that the BACDS can save a significant amount of energy and achieve up to longer network lifetime than previous schemes.

Polystyrene Backbone Polymers Consisting of Alkyl-Substituted Triazine Side Groups for Phosphorescent OLEDs

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Beatrice Ch. D. Salert

2012-01-01

Full Text Available This paper describes the synthesis of new electron-transporting styrene monomers and their corresponding polystyrenes all with a 2,4,6-triphenyl-1,3,5-triazine basic structure in the side group. The monomers differ in the alkyl substitution and in the meta-/paralinkage of the triazine to the polymer backbone. The thermal and spectroscopic properties of the new electron-transporting polymers are discussed in regard to their chemical structures. Phosphorescent OLEDs were prepared using the obtained electron-transporting polymers as the emissive layer material in blend systems together with a green iridium-based emitter 13 and a small molecule as an additional cohost with wideband gap characteristics (CoH-001. The performance of the OLEDs was characterized and discussed in regard to the chemical structure of the new electron-transporting polymers.

The determinants of bond angle variability in protein/peptide backbones: A comprehensive statistical/quantum mechanics analysis.

Science.gov (United States)

Improta, Roberto; Vitagliano, Luigi; Esposito, Luciana

2015-11-01

The elucidation of the mutual influence between peptide bond geometry and local conformation has important implications for protein structure refinement, validation, and prediction. To gain insights into the structural determinants and the energetic contributions associated with protein/peptide backbone plasticity, we here report an extensive analysis of the variability of the peptide bond angles by combining statistical analyses of protein structures and quantum mechanics calculations on small model peptide systems. Our analyses demonstrate that all the backbone bond angles strongly depend on the peptide conformation and unveil the existence of regular trends as function of ψ and/or φ. The excellent agreement of the quantum mechanics calculations with the statistical surveys of protein structures validates the computational scheme here employed and demonstrates that the valence geometry of protein/peptide backbone is primarily dictated by local interactions. Notably, for the first time we show that the position of the H(α) hydrogen atom, which is an important parameter in NMR structural studies, is also dependent on the local conformation. Most of the trends observed may be satisfactorily explained by invoking steric repulsive interactions; in some specific cases the valence bond variability is also influenced by hydrogen-bond like interactions. Moreover, we can provide a reliable estimate of the energies involved in the interplay between geometry and conformations. © 2015 Wiley Periodicals, Inc.

Solution structure and backbone dynamics of recombinant Cucurbita maxima trypsin inhibitor-V determined by NMR spectroscopy.

Science.gov (United States)

Liu, J; Prakash, O; Cai, M; Gong, Y; Huang, Y; Wen, L; Wen, J J; Huang, J K; Krishnamoorthi, R

1996-02-06

The solution structure of recombinant Cucurbita maxima trypsin inhibitor-V (rCMTI-V), whose N-terminal is unacetylated and carries an extra glycine residue, was determined by means of two-dimensional (2D) homo and 3D hetero NMR experiments in combination with a distance geometry and simulated annealing algorithm. A total of 927 interproton distances and 123 torsion angle constraints were utilized to generate 18 structures. The root mean squared deviation (RMSD) of the mean structure is 0.53 A for main-chain atoms and 0.95 A for all the non-hydrogen atoms of residues 3-40 and 49-67. The average structure of rCMTI-V is found to be almost the same as that of the native protein [Cai, M., Gong, Y., Kao, J.-L., & Krishnamoorthi, R. (1995) Biochemistry 34, 5201-5211]. The backbone dynamics of uniformly 15N-labeled rCMTI-V were characterized by 2D 1H-15N NMR methods. 15N spin-lattice and spin-spin relaxation rate constants (R1 and R2, respectively) and [1H]-15N steady-state heteronuclear Overhauser effect enhancements were measured for the peptide NH units and, using the model-free formalism [Lipari, G., & Szabo, A. (1982) J. Am. Chem. Soc. 104, 4546-4559, 4559-4570], the following parameters were determined: overall tumbling correlation time for the protein molecule (tau m), generalized order parameters for the individual N-H vectors (S2), effective correlation times for their internal motions (tau e), and terms to account for motions on a slower time scale (second) due to chemical exchange and/or conformational averaging (R(ex)). Most of the backbone NH groups of rCMTI-V are found to be highly constrained ((S2) = 0.83) with the exception of those in the binding loop (residues 41-48, (S2) = 0.71) and the N-terminal region ((S2) = 0.73). Main-chain atoms in these regions show large RMSD values in the average NMR structure. Residues involved in turns also appear to have more mobility ((S2) = 0.80). Dynamical properties of rCMTI-V were compared with those of two other

Optimized set of two-dimensional experiments for fast sequential assignment, secondary structure determination, and backbone fold validation of 13C/15N-labelled proteins

International Nuclear Information System (INIS)

Bersch, Beate; Rossy, Emmanuel; Coves, Jacques; Brutscher, Bernhard

2003-01-01

NMR experiments are presented which allow backbone resonance assignment, secondary structure identification, and in favorable cases also molecular fold topology determination from a series of two-dimensional 1 H- 15 N HSQC-like spectra. The 1 H- 15 N correlation peaks are frequency shifted by an amount ± ω X along the 15 N dimension, where ω X is the C α , C β , or H α frequency of the same or the preceding residue. Because of the low dimensionality (2D) of the experiments, high-resolution spectra are obtained in a short overall experimental time. The whole series of seven experiments can be performed in typically less than one day. This approach significantly reduces experimental time when compared to the standard 3D-based methods. The here presented methodology is thus especially appealing in the context of high-throughput NMR studies of protein structure, dynamics or molecular interfaces

Impact of Backbone Fluorination on π-Conjugated Polymers in Organic Photovoltaic Devices: A Review

Directory of Open Access Journals (Sweden)

Nicolas Leclerc

2016-01-01

Full Text Available Solution-processed bulk heterojunction solar cells have experienced a remarkable acceleration in performances in the last two decades, reaching power conversion efficiencies above 10%. This impressive progress is the outcome of a simultaneous development of more advanced device architectures and of optimized semiconducting polymers. Several chemical approaches have been developed to fine-tune the optoelectronics and structural polymer parameters required to reach high efficiencies. Fluorination of the conjugated polymer backbone has appeared recently to be an especially promising approach for the development of efficient semiconducting polymers. As a matter of fact, most currently best-performing semiconducting polymers are using fluorine atoms in their conjugated backbone. In this review, we attempt to give an up-to-date overview of the latest results achieved on fluorinated polymers for solar cells and to highlight general polymer properties’ evolution trends related to the fluorination of their conjugated backbone.

Cost-effectiveness analysis of dolutegravir plus backbone compared with raltegravir plus backbone, darunavir+ritonavir plus backbone and efavirenz/tenofovir/emtricitabine in treatment naïve and experienced HIV-positive patients

Directory of Open Access Journals (Sweden)

Restelli U

2017-06-01

Full Text Available Umberto Restelli,1,2 Giuliano Rizzardini,3,4 Andrea Antinori,5 Adriano Lazzarin,6 Marzia Bonfanti,1 Paolo Bonfanti,7 Davide Croce1,2 1Centre for Research on Health Economics, Social and Health Care Management, LIUC – Università Cattaneo, Castellanza, Varese, Italy; 2School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 3First and Second Divisions of Infectious Diseases, “Luigi Sacco” Hospital, Milan, Italy; 4School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 5National Institute for Infectious Diseases “L Spallanzani”, Rome, 6Department of Infectious Diseases, San Raffaele Scientific Institute, 7Department of Infectious and Tropical Diseases, A Manzoni Hospital, Lecco, Italy Background: In January 2014, the European Medicines Agency issued a marketing authorization for dolutegravir (DTG, a second-generation integrase strand transfer inhibitor for HIV treatment. The study aimed at determining the incremental cost-effectiveness ratio (ICER of the use of DTG+backbone compared with raltegravir (RAL+backbone, darunavir (DRV+ritonavir(r+backbone and efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC in HIV-positive treatment-naïve patients and compared with RAL+backbone in treatment-experienced patients, from the Italian National Health Service’s point of view.Materials and methods: A published Monte Carlo Individual Simulation Model (ARAMIS-DTG model was used to perform the analysis. Patients pass through mutually exclusive health states (defined in terms of diagnosis of HIV with or without opportunistic infections [OIs] and cardiovascular disease [CVD] and successive lines of therapy. The model considers costs (2014 and quality of life per monthly cycle in a lifetime horizon. Costs and quality-adjusted life years (QALYs are dependent on OI, CVD, AIDS events, adverse events and antiretroviral therapies.Results: In

Analysis of stationary availability factor of two-level backbone computer networks with arbitrary topology

Science.gov (United States)

Rahman, P. A.

2018-05-01

This scientific paper deals with the two-level backbone computer networks with arbitrary topology. A specialized method, offered by the author for calculation of the stationary availability factor of the two-level backbone computer networks, based on the Markov reliability models for the set of the independent repairable elements with the given failure and repair rates and the methods of the discrete mathematics, is also discussed. A specialized algorithm, offered by the author for analysis of the network connectivity, taking into account different kinds of the network equipment failures, is also observed. Finally, this paper presents an example of calculation of the stationary availability factor for the backbone computer network with the given topology.

Constructing Battery-Aware Virtual Backbones in Wireless Sensor Networks

Directory of Open Access Journals (Sweden)

Chi Ma

2007-05-01

Full Text Available A critical issue in battery-powered sensor networks is to construct energy efficient virtual backbones for network routing. Recent study in battery technology reveals that batteries tend to discharge more power than needed and reimburse the over-discharged power if they are recovered. In this paper we first provide a mathematical battery model suitable for implementation in sensor networks. We then introduce the concept of battery-aware connected dominating set (BACDS and show that in general the minimum BACDS (MBACDS can achieve longer lifetime than the previous backbone structures. Then we show that finding a MBACDS is NP-hard and give a distributed approximation algorithm to construct the BACDS. The resulting BACDS constructed by our algorithm is at most (8+Δopt size, where Δ is the maximum node degree and opt is the size of an optimal BACDS. Simulation results show that the BACDS can save a significant amount of energy and achieve up to 30% longer network lifetime than previous schemes.

Green IGP Link Weights for Energy-efficiency and Load-balancing in IP Backbone Networks

OpenAIRE

Francois, Frederic; Wang, Ning; Moessner, Klaus; Georgoulas, Stylianos; Xu, Ke

2013-01-01

The energy consumption of backbone networks has become a primary concern for network operators and regulators due to the pervasive deployment of wired backbone networks to meet the requirements of bandwidth-hungry applications. While traditional optimization of IGP link weights has been used in IP based load-balancing operations, in this paper we introduce a novel link weight setting algorithm, the Green Load-balancing Algorithm (GLA), which is able to jointly optimize both energy efficiency ...

Formation of 1D hierarchical structures composed of Ni{sub 3}S{sub 2} nanosheets on CNTs backbone for supercapacitors and photocatalytic H{sub 2} production

Energy Technology Data Exchange (ETDEWEB)

Zhu, Ting; Wu, Hao Bin; Wang, Yabo; Xu, Rong; Lou, Xiong Wen [David] [School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Singapore 637457 (Singapore)

2012-12-15

One-dimensional (1D) hierarchical structures composed of Ni{sub 3}S{sub 2} nanosheets grown on carbon nanotube (CNT) backbone (denoted as CNT rate at Ni{sub 3}S{sub 2}) are fabricated by a rational multi-step transformation route. The first step involves coating the CNT backbone with a layer of silica to form CNT rate at SiO{sub 2}, which serves as the substrate for the growth of nickel silicate (NiSilicate) nanosheets in the second step to form CNT rate at SiO{sub 2} rate at NiSilicate core-double shell 1D structures. Finally the as-formed CNT rate at SiO{sub 2} rate at NiSilicate 1D structures are converted into CNT-supported Ni{sub 3}S{sub 2} nanosheets via hydrothermal treatment in the presence of Na{sub 2}S. Simultaneously the intermediate silica layer is eliminated during the hydrothermal treatment, leading to the formation of CNT rate at Ni{sub 3}S{sub 2} nanostructures. Because of the unique hybrid nano-architecture, the as-prepared 1D hierarchical structure is shown to exhibit excellent performance in both supercapacitors and photocatalytic H{sub 2} production. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Backbone cup – a structure design competition based on topology optimization and 3D printing

Directory of Open Access Journals (Sweden)

Zhu Ji-Hong

2016-01-01

Full Text Available This paper addresses a structure design competition based on topology optimization and 3D Printing, and proposes an experimental approach to efficiently and quickly measure the mechanical performance of the structures designed using topology optimization. Since the topology optimized structure designs are prone to be geometrically complex, it is extremely inconvenient to fabricate these designs with traditional machining. In this study, we not only fabricated the topology optimized structure designs using one kind of 3D Printing technology known as stereolithography (SLA, but also tested the mechanical performance of the produced prototype parts. The finite element method is used to analyze the structure responses, and the consistent results of the numerical simulations and structure experiments prove the validity of this new structure testing approach. This new approach will not only provide a rapid access to topology optimized structure designs verifying, but also cut the turnaround time of structure design significantly.

Protein backbone angle restraints from searching a database for chemical shift and sequence homology

Energy Technology Data Exchange (ETDEWEB)

Cornilescu, Gabriel; Delaglio, Frank; Bax, Ad [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)

1999-03-15

Chemical shifts of backbone atoms in proteins are exquisitely sensitive to local conformation, and homologous proteins show quite similar patterns of secondary chemical shifts. The inverse of this relation is used to search a database for triplets of adjacent residues with secondary chemical shifts and sequence similarity which provide the best match to the query triplet of interest. The database contains 13C{alpha}, 13C{beta}, 13C', 1H{alpha} and 15N chemical shifts for 20 proteins for which a high resolution X-ray structure is available. The computer program TALOS was developed to search this database for strings of residues with chemical shift and residue type homology. The relative importance of the weighting factors attached to the secondary chemical shifts of the five types of resonances relative to that of sequence similarity was optimized empirically. TALOS yields the 10 triplets which have the closest similarity in secondary chemical shift and amino acid sequence to those of the query sequence. If the central residues in these 10 triplets exhibit similar {phi} and {psi} backbone angles, their averages can reliably be used as angular restraints for the protein whose structure is being studied. Tests carried out for proteins of known structure indicate that the root-mean-square difference (rmsd) between the output of TALOS and the X-ray derived backbone angles is about 15 deg. Approximately 3% of the predictions made by TALOS are found to be in error.

Protein backbone motions viewed by intraresidue and sequential H{sup N}-H{sup {alpha}} residual dipolar couplings

Energy Technology Data Exchange (ETDEWEB)

Voegeli, Beat; Yao Lishan; Bax, Ad [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)], E-mail: bax@nih.gov

2008-05-15

Triple resonance E.COSY-based techniques were used to measure intra-residue and sequential H{sup N}-H{sup {alpha}} residual dipolar couplings (RDCs) for the third IgG-binding domain of protein G (GB3), aligned in Pf1 medium. Measurements closely correlate with values predicted on the basis of an NMR structure, previously determined on the basis of a large number of one-bond backbone RDCs measured in five alignment media. However, in particular the sequential H{sup N}-H{sup {alpha}} RDCs are smaller than predicted for a static structure, suggesting a degree of motion for these internuclear vectors that exceeds that of the backbone amide N-H vectors. Of all experimentally determined GB3 structures available, the best correlation between experimental {sup 1}H-{sup 1}H couplings is observed for a GB3 ensemble, previously derived to generate a realistic picture of the conformational space sampled by GB3 (Clore and Schwieters, J Mol Biol 355:879-886, 2006). However, for both NMR and X-ray-derived structures the {sup 1}H-{sup 1}H couplings are found to be systematically smaller than expected on the basis of alignment tensors derived from {sup 15}N-{sup 1}H amide RDCs, assuming librationally corrected N-H bond lengths of 1.041 A.

Synonymous codon bias and functional constraint on GC3-related DNA backbone dynamics in the prokaryotic nucleoid.

Science.gov (United States)

Babbitt, Gregory A; Alawad, Mohammed A; Schulze, Katharina V; Hudson, André O

2014-01-01

While mRNA stability has been demonstrated to control rates of translation, generating both global and local synonymous codon biases in many unicellular organisms, this explanation cannot adequately explain why codon bias strongly tracks neighboring intergene GC content; suggesting that structural dynamics of DNA might also influence codon choice. Because minor groove width is highly governed by 3-base periodicity in GC, the existence of triplet-based codons might imply a functional role for the optimization of local DNA molecular dynamics via GC content at synonymous sites (≈GC3). We confirm a strong association between GC3-related intrinsic DNA flexibility and codon bias across 24 different prokaryotic multiple whole-genome alignments. We develop a novel test of natural selection targeting synonymous sites and demonstrate that GC3-related DNA backbone dynamics have been subject to moderate selective pressure, perhaps contributing to our observation that many genes possess extreme DNA backbone dynamics for their given protein space. This dual function of codons may impose universal functional constraints affecting the evolution of synonymous and non-synonymous sites. We propose that synonymous sites may have evolved as an 'accessory' during an early expansion of a primordial genetic code, allowing for multiplexed protein coding and structural dynamic information within the same molecular context. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Green Network Planning Model for Optical Backbones

DEFF Research Database (Denmark)

Gutierrez Lopez, Jose Manuel; Riaz, M. Tahir; Jensen, Michael

2010-01-01

on the environment in general. In network planning there are existing planning models focused on QoS provisioning, investment minimization or combinations of both and other parameters. But there is a lack of a model for designing green optical backbones. This paper presents novel ideas to be able to define......Communication networks are becoming more essential for our daily lives and critically important for industry and governments. The intense growth in the backbone traffic implies an increment of the power demands of the transmission systems. This power usage might have a significant negative effect...

Predicting the tolerated sequences for proteins and protein interfaces using RosettaBackrub flexible backbone design.

Directory of Open Access Journals (Sweden)

Colin A Smith

Full Text Available Predicting the set of sequences that are tolerated by a protein or protein interface, while maintaining a desired function, is useful for characterizing protein interaction specificity and for computationally designing sequence libraries to engineer proteins with new functions. Here we provide a general method, a detailed set of protocols, and several benchmarks and analyses for estimating tolerated sequences using flexible backbone protein design implemented in the Rosetta molecular modeling software suite. The input to the method is at least one experimentally determined three-dimensional protein structure or high-quality model. The starting structure(s are expanded or refined into a conformational ensemble using Monte Carlo simulations consisting of backrub backbone and side chain moves in Rosetta. The method then uses a combination of simulated annealing and genetic algorithm optimization methods to enrich for low-energy sequences for the individual members of the ensemble. To emphasize certain functional requirements (e.g. forming a binding interface, interactions between and within parts of the structure (e.g. domains can be reweighted in the scoring function. Results from each backbone structure are merged together to create a single estimate for the tolerated sequence space. We provide an extensive description of the protocol and its parameters, all source code, example analysis scripts and three tests applying this method to finding sequences predicted to stabilize proteins or protein interfaces. The generality of this method makes many other applications possible, for example stabilizing interactions with small molecules, DNA, or RNA. Through the use of within-domain reweighting and/or multistate design, it may also be possible to use this method to find sequences that stabilize particular protein conformations or binding interactions over others.

Backbone conformation affects duplex initiation and duplex propagation in hybridisation of synthetic H-bonding oligomers.

Science.gov (United States)

Iadevaia, Giulia; Núñez-Villanueva, Diego; Stross, Alexander E; Hunter, Christopher A

2018-06-06

Synthetic oligomers equipped with complementary H-bond donor and acceptor side chains form multiply H-bonded duplexes in organic solvents. Comparison of the duplex forming properties of four families of oligomers with different backbones shows that formation of an extended duplex with three or four inter-strand H-bonds is more challenging than formation of complexes that make only two H-bonds. The stabilities of 1 : 1 complexes formed between length complementary homo-oligomers equipped with either phosphine oxide or phenol recognition modules were measured in toluene. When the backbone is very flexible (pentane-1,5-diyl thioether), the stability increases uniformly by an order of magnitude for each additional base-pair added to the duplex: the effective molarities for formation of the first intramolecular H-bond (duplex initiation) and subsequent intramolecular H-bonds (duplex propagation) are similar. This flexible system is compared with three more rigid backbones that are isomeric combinations of an aromatic ring and methylene groups. One of the rigid systems behaves in exactly the same way as the flexible backbone, but the other two do not. For these systems, the effective molarity for formation of the first intramolecular H-bond is the same as that found for the other two backbones, but additional H-bonds are not formed between the longer oligomers. The effective molarities are too low for duplex propagation in these systems, because the oligomer backbones cannot adopt conformations compatible with formation of an extended duplex.

Protonation–deprotonation of the glycine backbone as followed by Raman scattering and multiconformational analysis

Energy Technology Data Exchange (ETDEWEB)

Hernández, Belén; Pflüger, Fernando [Groupe de Biophysique Moléculaire, UFR Santé-Médecine-Biologie Humaine, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny cedex (France); Kruglik, Sergei G. [Laboratoire Jean Perrin, FRE 3231, Université Pierre et Marie Curie (Paris 6), Case courrier 138, 75252 Paris Cedex 05 (France); Ghomi, Mahmoud, E-mail: mahmoud.ghomi@univ-paris13.fr [Groupe de Biophysique Moléculaire, UFR Santé-Médecine-Biologie Humaine, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny cedex (France)

2013-11-08

Highlights: • New pH-dependent Raman spectra in the middle wavenumber region (1800-300 cm{sup −1}). • New quantum mechanical calculations for exploring the Gly conformational landscape. • Construction of muticonformation based theoretical Raman spectra. - Abstract: Because of the absence of the side chain in its chemical structure and its well defined Raman spectra, glycine was selected here to follow its backbone protonation–deprotonation. The scan of the recorded spectra in the 1800–300 cm{sup −1} region led us to assign those obtained at pH 1, 6 and 12 to the cationic, zwitterionic and anionic species, respectively. These data complete well those previously published by Bykov et al. (2008) [16] devoted to the high wavenumber Raman spectra (>2500 cm{sup −1}). To reinforce our discussion, DFT calculations were carried out on the clusters of glycine + 5H{sub 2}O, mimicking reasonably the first hydration shell of the amino acid. Geometry optimization of 141 initial clusters, reflecting plausible combinations of the backbone torsion angles, allowed exploration of the conformational features, as well as construction of the theoretical Raman spectra by considering the most stable clusters containing each glycine species.

Quantitative assessments of the distinct contributions of polypeptide backbone amides versus sidechain groups to chain expansion via chemical denaturation

Science.gov (United States)

Holehouse, Alex S.; Garai, Kanchan; Lyle, Nicholas; Vitalis, Andreas; Pappu, Rohit V.

2015-01-01

In aqueous solutions with high concentrations of chemical denaturants such as urea and guanidinium chloride (GdmCl) proteins expand to populate heterogeneous conformational ensembles. These denaturing environments are thought to be good solvents for generic protein sequences because properties of conformational distributions align with those of canonical random coils. Previous studies showed that water is a poor solvent for polypeptide backbones and therefore backbones form collapsed globular structures in aqueous solvents. Here, we ask if polypeptide backbones can intrinsically undergo the requisite chain expansion in aqueous solutions with high concentrations of urea and GdmCl. We answer this question using a combination of molecular dynamics simulations and fluorescence correlation spectroscopy. We find that the degree of backbone expansion is minimal in aqueous solutions with high concentrations denaturants. Instead, polypeptide backbones sample conformations that are denaturant-specific mixtures of coils and globules, with a persistent preference for globules. Therefore, typical denaturing environments cannot be classified as good solvents for polypeptide backbones. How then do generic protein sequences expand in denaturing environments? To answer this question, we investigated the effects of sidechains using simulations of two archetypal sequences with amino acid compositions that are mixtures of charged, hydrophobic, and polar groups. We find that sidechains lower the effective concentration of backbone amides in water leading to an intrinsic expansion of polypeptide backbones in the absence of denaturants. Additional dilution of the effective concentration of backbone amides is achieved through preferential interactions with denaturants. These effects lead to conformational statistics in denaturing environments that are congruent with those of canonical random coils. Our results highlight the role of sidechain-mediated interactions as determinants of the

Experimental Tracking of Limit-Point Bifurcations and Backbone Curves Using Control-Based Continuation

Science.gov (United States)

Renson, Ludovic; Barton, David A. W.; Neild, Simon A.

Control-based continuation (CBC) is a means of applying numerical continuation directly to a physical experiment for bifurcation analysis without the use of a mathematical model. CBC enables the detection and tracking of bifurcations directly, without the need for a post-processing stage as is often the case for more traditional experimental approaches. In this paper, we use CBC to directly locate limit-point bifurcations of a periodically forced oscillator and track them as forcing parameters are varied. Backbone curves, which capture the overall frequency-amplitude dependence of the system’s forced response, are also traced out directly. The proposed method is demonstrated on a single-degree-of-freedom mechanical system with a nonlinear stiffness characteristic. Results are presented for two configurations of the nonlinearity — one where it exhibits a hardening stiffness characteristic and one where it exhibits softening-hardening.

Determination of backbone chain direction of PDA using FFM

Science.gov (United States)

Jo, Sadaharu; Okamoto, Kentaro; Takenaga, Mitsuru

2010-01-01

The effect of backbone chains on friction force was investigated on both Langmuir-Blodgett (LB) films of 10,12-heptacosadiynoic acid and the (0 1 0) surfaces of single crystals of 2,4-hexadiene-1,6-diol using friction force microscopy (FFM). It was observed that friction force decreased when the scanning direction was parallel to the [0 0 1] direction in both samples. Moreover, friction force decreased when the scanning direction was parallel to the crystallographic [1 0 2], [1 0 1], [1 0 0] and [1 0 1¯] directions in only the single crystals. For the LB films, the [0 0 1] direction corresponds to the backbone chain direction of 10,12-heptacosadiynoic acid. For the single crystals, both the [0 0 1] and [1 0 1] directions correspond to the backbone chain direction, and the [1 0 2], [1 0 0] and [1 0 1¯] directions correspond to the low-index crystallographic direction. In both the LB films and single crystals, the friction force was minimized when the directions of scanning and the backbone chain were parallel.

Self-assembly of diphenylalanine backbone homologues and their combination with functionalized carbon nanotubes.

Science.gov (United States)

Dinesh, Bhimareddy; Squillaci, Marco A; Ménard-Moyon, Cécilia; Samorì, Paolo; Bianco, Alberto

2015-10-14

The integration of carbon nanotubes (CNTs) into organized nanostructures is of great interest for applications in materials science and biomedicine. In this work we studied the self-assembly of β and γ homologues of diphenylalanine peptides under different solvent and pH conditions. We aimed to investigate the role of peptide backbone in tuning the formation of different types of nanostructures alone or in combination with carbon nanotubes. In spite of having the same side chain, β and γ peptides formed distinctively different nanofibers, a clear indication of the role played by the backbone homologation on the self-assembly. The variation of the pH allowed to transform the nanofibers into spherical structures. Moreover, the co-assembly of β and γ peptides with carbon nanotubes covalently functionalized with the same peptide generated unique dendritic assemblies. This comparative study on self-assembly using diphenylalanine backbone homologues and of the co-assembly with CNT covalent conjugates is the first example exploring the capacity of β and γ peptides to adopt precise nanostructures, particularly in combination with carbon nanotubes. The dendritic organization obtained by mixing carbon nanotubes and peptides might find interesting applications in tissue engineering and neuronal interfacing.

Protein backbone and sidechain torsion angles predicted from NMR chemical shifts using artificial neural networks

Energy Technology Data Exchange (ETDEWEB)

Shen Yang; Bax, Ad, E-mail: bax@nih.gov [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)

2013-07-15

A new program, TALOS-N, is introduced for predicting protein backbone torsion angles from NMR chemical shifts. The program relies far more extensively on the use of trained artificial neural networks than its predecessor, TALOS+. Validation on an independent set of proteins indicates that backbone torsion angles can be predicted for a larger, {>=}90 % fraction of the residues, with an error rate smaller than ca 3.5 %, using an acceptance criterion that is nearly two-fold tighter than that used previously, and a root mean square difference between predicted and crystallographically observed ({phi}, {psi}) torsion angles of ca 12 Masculine-Ordinal-Indicator . TALOS-N also reports sidechain {chi}{sup 1} rotameric states for about 50 % of the residues, and a consistency with reference structures of 89 %. The program includes a neural network trained to identify secondary structure from residue sequence and chemical shifts.

Electric field induced localization phenomena in a ladder network with superlattice configuration: Effect of backbone environment

Energy Technology Data Exchange (ETDEWEB)

Dutta, Paramita; Karmakar, S. N. [Condensed Matter Physics Division, Saha Institute of Nuclear Physics, Sector-I, Block-AF, Bidhannagar, Kolkata-700 064 (India); Maiti, Santanu K., E-mail: santanu.maiti@isical.ac.in [Physics and Applied Mathematics Unit, Indian Statistical Institute, 203 Barrackpore Trunk Road, Kolkata-700 108 (India)

2014-09-15

Electric field induced localization properties of a tight-binding ladder network in presence of backbone sites are investigated. Based on Green's function formalism we numerically calculate two-terminal transport together with density of states for different arrangements of atomic sites in the ladder and its backbone. Our results lead to a possibility of getting multiple mobility edges which essentially plays a switching action between a completely opaque to fully or partly conducting region upon the variation of system Fermi energy, and thus, support in fabricating mesoscopic or DNA-based switching devices.

Analysis of the HIV-2 protease's adaptation to various ligands: characterization of backbone asymmetry using a structural alphabet.

Science.gov (United States)

Triki, Dhoha; Cano Contreras, Mario Enrique; Flatters, Delphine; Visseaux, Benoit; Descamps, Diane; Camproux, Anne-Claude; Regad, Leslie

2018-01-15

The HIV-2 protease (PR2) is a homodimer of 99 residues with asymmetric assembly and binding various ligands. We propose an exhaustive study of the local structural asymmetry between the two monomers of all available PR2 structures complexed with various inhibitors using a structural alphabet approach. On average, PR2 exhibits asymmetry in 31% of its positions-i.e., exhibiting different backbone local conformations in the two monomers. This asymmetry was observed all along its structure, particularly in the elbow and flap regions. We first differentiated structural asymmetry conserved in most PR2 structures from the one specific to some PR2. Then, we explored the origin of the detected asymmetry in PR2. We localized asymmetry that could be induced by PR2's flexibility, allowing transition from the semi-open to closed conformations and the asymmetry potentially induced by ligand binding. This latter could be important for the PR2's adaptation to diverse ligands. Our results highlighted some differences between asymmetry of PR2 bound to darunavir and amprenavir that could explain their differences of affinity. This knowledge is critical for a better description of PR2's recognition and adaptation to various ligands and for a better understanding of the resistance of PR2 to most PR2 inhibitors, a major antiretroviral class.

Polystyrene Backbone Polymers Consisting of Alkyl-Substituted Triazine Side Groups for Phosphorescent OLEDs

OpenAIRE

Salert, Beatrice Ch. D.; Wedel, Armin; Grubert, Lutz; Eberle, Thomas; Anémian, Rémi; Krueger, Hartmut

2012-01-01

This paper describes the synthesis of new electron-transporting styrene monomers and their corresponding polystyrenes all with a 2,4,6-triphenyl-1,3,5-triazine basic structure in the side group. The monomers differ in the alkyl substitution and in the meta-/paralinkage of the triazine to the polymer backbone. The thermal and spectroscopic properties of the new electron-transporting polymers are discussed in regard to their chemical structures. Phosphorescent OLEDs were prepared using the obta...

The Graphical Representation of the Digital Astronaut Physiology Backbone

Science.gov (United States)

Briers, Demarcus

2010-01-01

This report summarizes my internship project with the NASA Digital Astronaut Project to analyze the Digital Astronaut (DA) physiology backbone model. The Digital Astronaut Project (DAP) applies integrated physiology models to support space biomedical operations, and to assist NASA researchers in closing knowledge gaps related to human physiologic responses to space flight. The DA physiology backbone is a set of integrated physiological equations and functions that model the interacting systems of the human body. The current release of the model is HumMod (Human Model) version 1.5 and was developed over forty years at the University of Mississippi Medical Center (UMMC). The physiology equations and functions are scripted in an XML schema specifically designed for physiology modeling by Dr. Thomas G. Coleman at UMMC. Currently it is difficult to examine the physiology backbone without being knowledgeable of the XML schema. While investigating and documenting the tags and algorithms used in the XML schema, I proposed a standard methodology for a graphical representation. This standard methodology may be used to transcribe graphical representations from the DA physiology backbone. In turn, the graphical representations can allow examination of the physiological functions and equations without the need to be familiar with the computer programming languages or markup languages used by DA modeling software.

TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts

Energy Technology Data Exchange (ETDEWEB)

Shen Yang; Delaglio, Frank [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Cornilescu, Gabriel [National Magnetic Resonance Facility (United States); Bax, Ad [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)], E-mail: bax@nih.gov

2009-08-15

NMR chemical shifts in proteins depend strongly on local structure. The program TALOS establishes an empirical relation between {sup 13}C, {sup 15}N and {sup 1}H chemical shifts and backbone torsion angles {phi} and {psi} (Cornilescu et al. J Biomol NMR 13 289-302, 1999). Extension of the original 20-protein database to 200 proteins increased the fraction of residues for which backbone angles could be predicted from 65 to 74%, while reducing the error rate from 3 to 2.5%. Addition of a two-layer neural network filter to the database fragment selection process forms the basis for a new program, TALOS+, which further enhances the prediction rate to 88.5%, without increasing the error rate. Excluding the 2.5% of residues for which TALOS+ makes predictions that strongly differ from those observed in the crystalline state, the accuracy of predicted {phi} and {psi} angles, equals {+-}13{sup o}. Large discrepancies between predictions and crystal structures are primarily limited to loop regions, and for the few cases where multiple X-ray structures are available such residues are often found in different states in the different structures. The TALOS+ output includes predictions for individual residues with missing chemical shifts, and the neural network component of the program also predicts secondary structure with good accuracy.

Thin Films Formed from Conjugated Polymers with Ionic, Water-Soluble Backbones

NARCIS (Netherlands)

Voortman, Thomas P; Chiechi, Ryan C

2015-01-01

This paper compares the morphologies of films of conjugated polymers in which the backbone (main chain) and pendant groups are varied between ionic/hydrophilic and aliphatic/hydrophobic. We observe that conjugated polymers in which the pendant groups and backbone are matched, either ionic-ionic or

Gender features of functional condition of backbone of teenagers with scoliotic posture

Directory of Open Access Journals (Sweden)

Sergiy Afanasiev

2016-10-01

Full Text Available Purpose: to study mobility of backbone, endurance of muscles of a trunk and to define gender features of functional condition of backbone at children of the middle school age with scoliotic posture depending on the direction of the top of arch of curvature of spine. Material & Methods: 40 girls and 40 boys, including 18 girls and 18 boys with the right-side deformation of backbone in the thoracic department, the left-side – 22 girls and 22 boys are examined. Results: features of changes of indicators, depending on sex of children and frontage of the top of arch of curvature of spine column, are revealed when studying the level of flexibility of backbone and endurance of muscles of a trunk at children of the middle school age with scoliotic posture. Conclusions: it is established that the level of decrease in flexibility of backbone is higher at boys, than at girls, whereas indicators of contractile ability and tone of muscles of "muscular corset" are higher at boys.

Structure-Based Design of Novel HIV-1 Protease Inhibitors to Combat Drug Resistance

Energy Technology Data Exchange (ETDEWEB)

Ghosh,A.; Sridhar, P.; Leshchenko, S.; Hussain, A.; Li, J.; Kovalevsky, A.; Walters, D.; Wedelind, J.; Grum-Tokars, V.; et al.

2006-01-01

Structure-based design and synthesis of novel HIV protease inhibitors are described. The inhibitors are designed specifically to interact with the backbone of HIV protease active site to combat drug resistance. Inhibitor 3 has exhibited exceedingly potent enzyme inhibitory and antiviral potency. Furthermore, this inhibitor maintains impressive potency against a wide spectrum of HIV including a variety of multi-PI-resistant clinical strains. The inhibitors incorporated a stereochemically defined 5-hexahydrocyclopenta[b]furanyl urethane as the P2-ligand into the (R)-(hydroxyethylamino)sulfonamide isostere. Optically active (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[b]furan was prepared by an enzymatic asymmetrization of meso-diacetate with acetyl cholinesterase, radical cyclization, and Lewis acid-catalyzed anomeric reduction as the key steps. A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 Angstroms resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance.

Assignment by Negative-Ion Electrospray Tandem Mass Spectrometry of the Tetrasaccharide Backbones of Monosialylated Glycans Released from Bovine Brain Gangliosides

Science.gov (United States)

Chai, Wengang; Zhang, Yibing; Mauri, Laura; Ciampa, Maria G.; Mulloy, Barbara; Sonnino, Sandro; Feizi, Ten

2018-05-01

Gangliosides, as plasma membrane-associated sialylated glycolipids, are antigenic structures and they serve as ligands for adhesion proteins of pathogens, for toxins of bacteria, and for endogenous proteins of the host. The detectability by carbohydrate-binding proteins of glycan antigens and ligands on glycolipids can be influenced by the differing lipid moieties. To investigate glycan sequences of gangliosides as recognition structures, we have underway a program of work to develop a "gangliome" microarray consisting of isolated natural gangliosides and neoglycolipids (NGLs) derived from glycans released from them, and each linked to the same lipid molecule for arraying and comparative microarray binding analyses. Here, in the first phase of our studies, we describe a strategy for high-sensitivity assignment of the tetrasaccharide backbones and application to identification of eight of monosialylated glycans released from bovine brain gangliosides. This approach is based on negative-ion electrospray mass spectrometry with collision-induced dissociation (ESI-CID-MS/MS) of the desialylated glycans. Using this strategy, we have the data on backbone regions of four minor components among the monosialo-ganglioside-derived glycans; these are of the ganglio-, lacto-, and neolacto-series.

Effect of backbone chemistry on hybridization thermodynamics of oligonucleic acids: a coarse-grained molecular dynamics simulation study.

Science.gov (United States)

Ghobadi, Ahmadreza F; Jayaraman, Arthi

2016-02-28

In this paper we study how varying oligonucleic acid backbone chemistry affects the hybridization/melting thermodynamics of oligonucleic acids. We first describe the coarse-grained (CG) model with tunable parameters that we developed to enable the study of both naturally occurring oligonucleic acids, such as DNA, and their chemically-modified analogues, such as peptide nucleic acids (PNAs) and locked nucleic acids (LNAs). The DNA melting curves obtained using such a CG model and molecular dynamics simulations in an implicit solvent and with explicit ions match with the melting curves obtained using the empirical nearest-neighbor models. We use these CG simulations to then elucidate the effect of backbone flexibility, charge, and nucleobase spacing along the backbone on the melting curves, potential energy and conformational entropy change upon hybridization and base-pair hydrogen bond residence time. We find that increasing backbone flexibility decreases duplex thermal stability and melting temperature mainly due to increased conformational entropy loss upon hybridization. Removing charges from the backbone enhances duplex thermal stability due to the elimination of electrostatic repulsion and as a result a larger energetic gain upon hybridization. Lastly, increasing nucleobase spacing decreases duplex thermal stability due to decreasing stacking interactions that are important for duplex stability.

Conformation-specific spectroscopy of capped glutamine-containing peptides: role of a single glutamine residue on peptide backbone preferences.

Science.gov (United States)

Walsh, Patrick S; Dean, Jacob C; McBurney, Carl; Kang, Hyuk; Gellman, Samuel H; Zwier, Timothy S

2016-04-28

The conformational preferences of a series of short, aromatic-capped, glutamine-containing peptides have been studied under jet-cooled conditions in the gas phase. This work seeks a bottom-up understanding of the role played by glutamine residues in directing peptide structures that lead to neurodegenerative diseases. Resonant ion-dip infrared (RIDIR) spectroscopy is used to record single-conformation infrared spectra in the NH stretch, amide I and amide II regions. Comparison of the experimental spectra with the predictions of calculations carried out at the DFT M05-2X/6-31+G(d) level of theory lead to firm assignments for the H-bonding architectures of a total of eight conformers of four molecules, including three in Z-Gln-OH, one in Z-Gln-NHMe, three in Ac-Gln-NHBn, and one in Ac-Ala-Gln-NHBn. The Gln side chain engages actively in forming H-bonds with nearest-neighbor amide groups, forming C8 H-bonds to the C-terminal side, C9 H-bonds to the N-terminal side, and an amide-stacked geometry, all with an extended (C5) peptide backbone about the Gln residue. The Gln side chain also stabilizes an inverse γ-turn in the peptide backbone by forming a pair of H-bonds that bridge the γ-turn and stabilize it. Finally, the entire conformer population of Ac-Ala-Gln-NHBn is funneled into a single structure that incorporates the peptide backbone in a type I β-turn, stabilized by the Gln side chain forming a C7 H-bond to the central amide group in the β-turn not otherwise involved in a hydrogen bond. This β-turn backbone structure is nearly identical to that observed in a series of X-(AQ)-Y β-turns in the protein data bank, demonstrating that the gas-phase structure is robust to perturbations imposed by the crystalline protein environment.

Chemical characteristics and antithrombotic effect of chondroitin sulfates from sturgeon skull and sturgeon backbone.

Science.gov (United States)

Gui, Meng; Song, Juyi; Zhang, Lu; Wang, Shun; Wu, Ruiyun; Ma, Changwei; Li, Pinglan

2015-06-05

Chondroitin sulfates (CSs) were extracted from sturgeon skull and backbone, and their chemical composition, anticoagulant, anti-platelet and thrombolysis activities were evaluated. The average molecular weights of CS from sturgeon skull and backbone were 38.5kDa and 49.2kDa, respectively. Disaccharide analysis indicated that the sturgeon backbone CS was primarily composed of disaccharide monosulfated in position four of the GalNAc (37.8%) and disaccharide monosulfated in position six of the GalNAc (59.6%) while sturgeon skull CS was primarily composed of nonsulfated disaccharide (74.2%). Sturgeon backbone CS showed stronger antithrombotic effect than sturgeon skull CS. Sturgeon backbone CS could significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT), inhibited ADP-induced platelet aggregation and dissolved platelet plasma clots in vitro. The results suggested that sturgeon backbone CS can be explored as a functional food with antithrombotic function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Smart-Grid Backbone Network Real-Time Delay Reduction via Integer Programming.

Science.gov (United States)

Pagadrai, Sasikanth; Yilmaz, Muhittin; Valluri, Pratyush

2016-08-01

This research investigates an optimal delay-based virtual topology design using integer linear programming (ILP), which is applied to the current backbone networks such as smart-grid real-time communication systems. A network traffic matrix is applied and the corresponding virtual topology problem is solved using the ILP formulations that include a network delay-dependent objective function and lightpath routing, wavelength assignment, wavelength continuity, flow routing, and traffic loss constraints. The proposed optimization approach provides an efficient deterministic integration of intelligent sensing and decision making, and network learning features for superior smart grid operations by adaptively responding the time-varying network traffic data as well as operational constraints to maintain optimal virtual topologies. A representative optical backbone network has been utilized to demonstrate the proposed optimization framework whose simulation results indicate that superior smart-grid network performance can be achieved using commercial networks and integer programming.

Investigation of novel solid oxide fuel cell cathodes based on impregnation of SrTixFe1-xO3-δ into ceria-based backbones

DEFF Research Database (Denmark)

Brinch-Larsen, Mathias; Søgaard, Martin; Hjelm, Johan

2013-01-01

Solid oxide fuel cell (SOFC) cathodes were prepared by impregnating the nitrates corresponding to SrTixFe1-xO3-δ (STF), x= 0; 0.1; 0.2; 0.3; 0.4 and 0.5, into a porous backbone of Ce 0.9Gd0.1O2-δ (CGO). STF was chosen as very high oxygen surface exchange rate, high ionic conductivity and electroc......Solid oxide fuel cell (SOFC) cathodes were prepared by impregnating the nitrates corresponding to SrTixFe1-xO3-δ (STF), x= 0; 0.1; 0.2; 0.3; 0.4 and 0.5, into a porous backbone of Ce 0.9Gd0.1O2-δ (CGO). STF was chosen as very high oxygen surface exchange rate, high ionic conductivity...... backbone. All prepared electrodes were characterized as symmetric cells using impedance spectroscopy. Within the investigated series the infiltrate with x = 0.1 (STF10) showed the best performance with an area specific resistance (ASR) of ASR ≈ 6.4 Ω cm2 (STF10) at 600°C in air. The relatively poor...

Direct observation of backbone planarization via side-chain alignment in single bulky-substituted polythiophenes

Science.gov (United States)

Raithel, Dominic; Simine, Lena; Pickel, Sebastian; Schötz, Konstantin; Panzer, Fabian; Baderschneider, Sebastian; Schiefer, Daniel; Lohwasser, Ruth; Köhler, Jürgen; Thelakkat, Mukundan; Sommer, Michael; Köhler, Anna; Rossky, Peter J.; Hildner, Richard

2018-03-01

The backbone conformation of conjugated polymers affects, to a large extent, their optical and electronic properties. The usually flexible substituents provide solubility and influence the packing behavior of conjugated polymers in films or in bad solvents. However, the role of the side chains in determining and potentially controlling the backbone conformation, and thus the optical and electronic properties on the single polymer level, is currently under debate. Here, we investigate directly the impact of the side chains by studying the bulky-substituted poly(3-(2,5-dioctylphenyl)thiophene) (PDOPT) and the common poly(3-hexylthiophene) (P3HT), both with a defined molecular weight and high regioregularity, using low-temperature single-chain photoluminescence (PL) spectroscopy and quantum-classical simulations. Surprisingly, the optical transition energy of PDOPT is significantly (˜2,000 cm‑1 or 0.25 eV) red-shifted relative to P3HT despite a higher static and dynamic disorder in the former. We ascribe this red shift to a side-chain induced backbone planarization in PDOPT, supported by temperature-dependent ensemble PL spectroscopy. Our atomistic simulations reveal that the bulkier 2,5-dioctylphenyl side chains of PDOPT adopt a clear secondary helical structural motif and thus protect conjugation, i.e., enforce backbone planarity, whereas, for P3HT, this is not the case. These different degrees of planarity in both thiophenes do not result in different conjugation lengths, which we found to be similar. It is rather the stronger electronic coupling between the repeating units in the more planar PDOPT which gives rise to the observed spectral red shift as well as to a reduced calculated electron‑hole polarization.

A fusion networking model for smart grid power distribution backbone communication network based on PTN

Directory of Open Access Journals (Sweden)

Wang Hao

2016-01-01

Full Text Available In current communication network for distribution in Chinese power grid systems, the fiber communication backbone network for distribution and TD-LTE power private wireless backhaul network of power grid are both bearing by the SDH optical transmission network, which also carries the communication network of transformer substation and main electric. As the data traffic of the distribution communication and TD-LTE power private wireless network grow rapidly in recent years, it will have a big impact with the SDH network’s bearing capacity which is mainly used for main electric communication in high security level. This paper presents a fusion networking model which use a multiple-layer PTN network as the unified bearing of the TD-LTE power private wireless backhaul network and fiber communication backbone network for distribution. Network dataflow analysis shows that this model can greatly reduce the capacity pressure of the traditional SDH network as well as ensure the reliability of the transmission of the communication network for distribution and TD-LTE power private wireless network.

A framework to find the logic backbone of a biological network.

Science.gov (United States)

Maheshwari, Parul; Albert, Réka

2017-12-06

Cellular behaviors are governed by interaction networks among biomolecules, for example gene regulatory and signal transduction networks. An often used dynamic modeling framework for these networks, Boolean modeling, can obtain their attractors (which correspond to cell types and behaviors) and their trajectories from an initial state (e.g. a resting state) to the attractors, for example in response to an external signal. The existing methods however do not elucidate the causal relationships between distant nodes in the network. In this work, we propose a simple logic framework, based on categorizing causal relationships as sufficient or necessary, as a complement to Boolean networks. We identify and explore the properties of complex subnetworks that are distillable into a single logic relationship. We also identify cyclic subnetworks that ensure the stabilization of the state of participating nodes regardless of the rest of the network. We identify the logic backbone of biomolecular networks, consisting of external signals, self-sustaining cyclic subnetworks (stable motifs), and output nodes. Furthermore, we use the logic framework to identify crucial nodes whose override can drive the system from one steady state to another. We apply these techniques to two biological networks: the epithelial-to-mesenchymal transition network corresponding to a developmental process exploited in tumor invasion, and the network of abscisic acid induced stomatal closure in plants. We find interesting subnetworks with logical implications in these networks. Using these subgraphs and motifs, we efficiently reduce both networks to succinct backbone structures. The logic representation identifies the causal relationships between distant nodes and subnetworks. This knowledge can form the basis of network control or used in the reverse engineering of networks.

Characterizing structural transitions using localized free energy landscape analysis.

Directory of Open Access Journals (Sweden)

Nilesh K Banavali

Full Text Available Structural changes in molecules are frequently observed during biological processes like replication, transcription and translation. These structural changes can usually be traced to specific distortions in the backbones of the macromolecules involved. Quantitative energetic characterization of such distortions can greatly advance the atomic-level understanding of the dynamic character of these biological processes.Molecular dynamics simulations combined with a variation of the Weighted Histogram Analysis Method for potential of mean force determination are applied to characterize localized structural changes for the test case of cytosine (underlined base flipping in a GTCAGCGCATGG DNA duplex. Free energy landscapes for backbone torsion and sugar pucker degrees of freedom in the DNA are used to understand their behavior in response to the base flipping perturbation. By simplifying the base flipping structural change into a two-state model, a free energy difference of upto 14 kcal/mol can be attributed to the flipped state relative to the stacked Watson-Crick base paired state. This two-state classification allows precise evaluation of the effect of base flipping on local backbone degrees of freedom.The calculated free energy landscapes of individual backbone and sugar degrees of freedom expectedly show the greatest change in the vicinity of the flipping base itself, but specific delocalized effects can be discerned upto four nucleotide positions away in both 5' and 3' directions. Free energy landscape analysis thus provides a quantitative method to pinpoint the determinants of structural change on the atomic scale and also delineate the extent of propagation of the perturbation along the molecule. In addition to nucleic acids, this methodology is anticipated to be useful for studying conformational changes in all macromolecules, including carbohydrates, lipids, and proteins.

Effect of oligonucleic acid (ONA) backbone features on assembly of ONA-star polymer conjugates: a coarse-grained molecular simulation study.

Science.gov (United States)

Condon, Joshua E; Jayaraman, Arthi

2017-10-04

Understanding the impact of incorporating new physical and chemical features in oligomeric DNA mimics, termed generally as "oligonucleic acids" (ONAs), on their structure and thermodynamics will be beneficial in designing novel materials for a variety of applications. In this work, we conduct coarse-grained molecular simulations of ONA-star polymer conjugates with varying ONA backbone flexibility, ONA backbone charge, and number of arms in the star polymer at a constant ONA strand volume fraction to elucidate the effect of these design parameters on the thermodynamics and assembly of multi-arm ONA-star polymer conjugates. We quantify the thermo-reversible behavior of the ONA-star polymer conjugates by quantifying the hybridization of the ONA strands in the system as a function of temperature (i.e. melting curve). Additionally, we characterize the assembly of the ONA-star polymer conjugates by tracking cluster formation and percolation as a function of temperature, as well as cluster size distribution at temperatures near the assembly transition region. The key results are as follows. The melting temperature (T m ) of the ONA strands decreases upon going from a neutral to a charged ONA backbone and upon increasing flexibility of the ONA backbone. Similar behavior is seen for the assembly transition temperature (T a ) with varying ONA backbone charge and flexibility. While the number of arms in the ONA-star polymer conjugate has a negligible effect on the ONA T m in these systems, as the number of ONA-star polymer arms increase, the assembly temperature T a increases and local ordering in the assembled state improves. By understanding how factors like ONA backbone charge, backbone flexibility, and ONA-star polymer conjugate architecture impact the behavior of ONA-star polymer conjugate systems, we can better inform how the selection of ONA chemistry will influence resulting ONA-star polymer assembly.

Cyclen-based double-tailed lipids for DNA delivery: Synthesis and the effect of linking group structures.

Science.gov (United States)

Zhang, Yi-Mei; Chang, De-Chun; Zhang, Ji; Liu, Yan-Hong; Yu, Xiao-Qi

2015-09-01

The gene transfection efficiency (TE) of cationic lipids is largely influenced by the lipid structure. Six novel 1, 4, 7, 10-tetraazacyclododecane (cyclen)-based cationic lipids L1-L6, which contain double oleyl as hydrophobic tails, were designed and synthesized. The difference between these lipids is their diverse backbone. Liposomes prepared by the lipids and DOPE showed good DNA affinity, and full DNA condensation could be achieved at N/P of 4 to form lipoplexes with proper size and zeta-potentials for gene transfection. Structure-activity relationship of these lipids as non-viral gene delivery vectors was investigated. It was found that minor backbone structural variations, including linking group and the structural symmetry would affect the TE. The diethylenetriamine derived lipid L4 containing amide linking bonds gave the best TE, which was several times higher than commercially available transfection reagent lipofectamine 2000. Besides, these lipids exhibited low cytotoxicity, suggesting their good biocompatibility. Results reveal that such type of cationic lipids might be promising non-viral gene vectors, and also afford us clues for the design of novel vectors with higher TE and biocompatibility. Copyright © 2015 Elsevier Ltd. All rights reserved.

Uganda's National Transmission Backbone Infrastructure Project: Technical Challenges and the Way Forward

Science.gov (United States)

Bulega, T.; Kyeyune, A.; Onek, P.; Sseguya, R.; Mbabazi, D.; Katwiremu, E.

2011-10-01

Several publications have identified technical challenges facing Uganda's National Transmission Backbone Infrastructure project. This research addresses the technical limitations of the National Transmission Backbone Infrastructure project, evaluates the goals of the project, and compares the results against the technical capability of the backbone. The findings of the study indicate a bandwidth deficit, which will be addressed by using dense wave division multiplexing repeaters, leasing bandwidth from private companies. Microwave links for redundancy, a Network Operation Center for operation and maintenance, and deployment of wireless interoperability for microwave access as a last-mile solution are also suggested.

Protein backbone chemical shifts predicted from searching a database for torsion angle and sequence homology

International Nuclear Information System (INIS)

Shen Yang; Bax, Ad

2007-01-01

Chemical shifts of nuclei in or attached to a protein backbone are exquisitely sensitive to their local environment. A computer program, SPARTA, is described that uses this correlation with local structure to predict protein backbone chemical shifts, given an input three-dimensional structure, by searching a newly generated database for triplets of adjacent residues that provide the best match in φ/ψ/χ 1 torsion angles and sequence similarity to the query triplet of interest. The database contains 15 N, 1 H N , 1 H α , 13 C α , 13 C β and 13 C' chemical shifts for 200 proteins for which a high resolution X-ray (≤2.4 A) structure is available. The relative importance of the weighting factors for the φ/ψ/χ 1 angles and sequence similarity was optimized empirically. The weighted, average secondary shifts of the central residues in the 20 best-matching triplets, after inclusion of nearest neighbor, ring current, and hydrogen bonding effects, are used to predict chemical shifts for the protein of known structure. Validation shows good agreement between the SPARTA-predicted and experimental shifts, with standard deviations of 2.52, 0.51, 0.27, 0.98, 1.07 and 1.08 ppm for 15 N, 1 H N , 1 H α , 13 C α , 13 C β and 13 C', respectively, including outliers

Redox-controlled backbone dynamics of human cytochrome c revealed by 15N NMR relaxation measurements

International Nuclear Information System (INIS)

Sakamoto, Koichi; Kamiya, Masakatsu; Uchida, Takeshi; Kawano, Keiichi; Ishimori, Koichiro

2010-01-01

Research highlights: → The dynamic parameters for the backbone dynamics in Cyt c were determined. → The backbone mobility of Cyt c is highly restricted due to the covalently bound heme. → The backbone mobility of Cyt c is more restricted upon the oxidation of the heme. → The redox-dependent dynamics are shown in the backbone of Cyt c. → The backbone dynamics of Cyt c would regulate the electron transfer from Cyt c. -- Abstract: Redox-controlled backbone dynamics in cytochrome c (Cyt c) were revealed by 2D 15 N NMR relaxation experiments. 15 N T 1 and T 2 values and 1 H- 15 N NOEs of uniformly 15 N-labeled reduced and oxidized Cyt c were measured, and the generalized order parameters (S 2 ), the effective correlation time for internal motion (τ e ), the 15 N exchange broadening contributions (R ex ) for each residue, and the overall correlation time (τ m ) were estimated by model-free dynamics formalism. These dynamic parameters clearly showed that the backbone dynamics of Cyt c are highly restricted due to the covalently bound heme that functions as the stable hydrophobic core. Upon oxidation of the heme iron in Cyt c, the average S 2 value was increased from 0.88 ± 0.01 to 0.92 ± 0.01, demonstrating that the mobility of the backbone is further restricted in the oxidized form. Such increases in the S 2 values were more prominent in the loop regions, including amino acid residues near the thioether bonds to the heme moiety and positively charged region around Lys87. Both of the regions are supposed to form the interaction site for cytochrome c oxidase (CcO) and the electron pathway from Cyt c to CcO. The redox-dependent mobility of the backbone in the interaction site for the electron transfer to CcO suggests an electron transfer mechanism regulated by the backbone dynamics in the Cyt c-CcO system.

TACN-based cationic lipids with amino acid backbone and double tails: materials for non-viral gene delivery.

Science.gov (United States)

Wang, Bing; Yi, Wen-Jing; Zhang, Ji; Zhang, Qin-Fang; Xun, Miao-Miao; Yu, Xiao-Qi

2014-04-01

Cationic lipids have become an efficient type of non-viral vectors for gene delivery. In this Letter, four cationic lipids containing 1,4,7-triazacyclononane (TACN) headgroup, glutamic/aspartic acid backbone and dioleyl tails were designed and synthesized. The TACN headgroup gives these lipids excellent pH buffering capacities, which were higher than branched 25 kDa PEI. Cationic liposomes prepared from these lipids and DOPE showed good DNA affinity, and full DNA condensation was found at N/P ratio of 3 via agarose gel electrophoresis. The lipoplexes were characterized by dynamic light scattering (DLS) assay, which gave proper particle sizes and zeta-potentials for transfection. In vitro gene transfection results in two cell lines reveal that TAN (with aspartic acid and amide bond in the structure) shows the best transfection efficiency, which is close to commercially available transfection agent Lipofectamine 2000. Copyright © 2014 Elsevier Ltd. All rights reserved.

Beta-scission of alkoxyl radicals on peptides and proteins can give rise to backbone cleavage and loss of side-chains

International Nuclear Information System (INIS)

Headlam, H.A.; Davies, M.J.; Mortimer, A.; Easton, C.J.

2000-01-01

Full text: Exposure of proteins to radicals in the presence of O 2 brings about multiple changes including side-chain oxidation, backbone fragmentation, cross-linking, unfolding, changes in hydrophobicity and conformation, altered susceptibility to proteolytic enzymes and formation of new reactive groups (e.g. hydroperoxides and 3,4-dihydroxyphenylalanine). All of these processes can result in loss of structural or enzymatic activity. The mechanisms that give rise to backbone cleavage are only partly understood. Whilst it is known that direct hydrogen atom abstraction at a-carbon sites gives backbone cleavages it has also been proposed that initial attack at side-chain sites might also give rise to backbone cleavage. In this study we have examined whether initial attack at the β- (C-3) position can give rise to α-carbon radicals (and hence backbone cleavage) via the formation, and subsequent β- scission, of C-3 alkoxyl radicals. This process has been observed previously with protected amino acids in organic solvents (J. Chem. Soc. Perkin Trans. 2, 1997, 503-507) but the occurrence of such reactions with proteins in aqueous solution has not been explored. Alkoxyl radicals were generated at the C-3 position of a variety of protected amino acids and small peptides by two methods: metal-ion catalysed decomposition of hydroperoxides formed as a result of γ-radiolysis in the presence of O 2 , and UV photolysis of nitrate esters. In most cases radicals have been detected by EPR spectroscopy using nitroso and nitrone spin traps, which can be assigned by comparison with literature data to α-carbon radicals; in some case assignments were confirmed by the generation of the putative species by other routes. With Ala peptide hydroperoxides and nitrate esters, and MNP as the spin trap, the major radical detected in each case has been assigned to the adduct of an α-carbon radical with partial structure - NH- . CH-C(O) - consistent with the rapid occurrence of the above

Control of polymer-packing orientation in thin films through synthetic tailoring of backbone coplanarity

KAUST Repository

Chen, Mark S.

2013-10-22

Controlling solid-state order of π-conjugated polymers through macromolecular design is essential for achieving high electronic device performance; yet, it remains a challenge, especially with respect to polymer-packing orientation. Our work investigates the influence of backbone coplanarity on a polymer\\'s preference to pack face-on or edge-on relative to the substrate. Isoindigo-based polymers were synthesized with increasing planarity by systematically substituting thiophenes for phenyl rings in the acceptor comonomer. This increasing backbone coplanarity, supported by density functional theory (DFT) calculations of representative trimers, leads to the narrowing of polymer band gaps as characterized by ultraviolet-visible-near infrared (UV-vis-NIR) spectroscopy and cyclic voltammetry. Among the polymers studied, regiosymmetric II and TII polymers exhibited the highest hole mobilities in organic field-effect transistors (OFETs), while in organic photovoltaics (OPVs), TBII polymers that display intermediate levels of planarity provided the highest power conversion efficiencies. Upon thin-film analysis by atomic force microscropy (AFM) and grazing-incidence X-ray diffraction (GIXD), we discovered that polymer-packing orientation could be controlled by tuning polymer planarity and solubility. Highly soluble, planar polymers favor face-on orientation in thin films while the less soluble, nonplanar polymers favor an edge-on orientation. This study advances our fundamental understanding of how polymer structure influences nanostructural order and reveals a new synthetic strategy for the design of semiconducting materials with rationally engineered solid-state properties. © 2013 American Chemical Society.

The Role of Backbone Hydrogen Bonds in the Transition State for Protein Folding of a PDZ Domain.

Directory of Open Access Journals (Sweden)

Søren W. Pedersen

Full Text Available Backbone hydrogen bonds are important for the structure and stability of proteins. However, since conventional site-directed mutagenesis cannot be applied to perturb the backbone, the contribution of these hydrogen bonds in protein folding and stability has been assessed only for a very limited set of small proteins. We have here investigated effects of five amide-to-ester mutations in the backbone of a PDZ domain, a 90-residue globular protein domain, to probe the influence of hydrogen bonds in a β-sheet for folding and stability. The amide-to-ester mutation removes NH-mediated hydrogen bonds and destabilizes hydrogen bonds formed by the carbonyl oxygen. The overall stability of the PDZ domain generally decreased for all amide-to-ester mutants due to an increase in the unfolding rate constant. For this particular region of the PDZ domain, it is therefore clear that native hydrogen bonds are formed after crossing of the rate-limiting barrier for folding. Moreover, three of the five amide-to-ester mutants displayed an increase in the folding rate constant suggesting that the hydrogen bonds are involved in non-native interactions in the transition state for folding.

Molecular Data for a Biochemical Model of DNA Radiation Damage: Electron Impact Ionization and Dissociative Ionization of DNA Bases and Sugar-Phosphate Backbone

Science.gov (United States)

Dateo, Christopher E.; Fletcher, Graham D.

2004-01-01

As part of the database for building up a biochemical model of DNA radiation damage, electron impact ionization cross sections of sugar-phosphate backbone and DNA bases have been calculated using the improved binary-encounter dipole (iBED) model. It is found that the total ionization cross sections of C3'- and C5'-deoxyribose-phospate, two conformers of the sugar-phosphate backbone, are close to each other. Furthermore, the sum of the ionization cross sections of the separate deoxyribose and phosphate fragments is in close agreement with the C3'- and C5'-deoxyribose-phospate cross sections, differing by less than 10%. Of the four DNA bases, the ionization cross section of guanine is the largest, then in decreasing order, adenine, thymine, and cytosine. The order is in accordance with the known propensity of oxidation of the bases by ionizing radiation. Dissociative ionization (DI), a process that both ionizes and dissociates a molecule, is investigated for cytosine. The DI cross section for the formation of H and (cytosine-Hl)(+), with the cytosine ion losing H at the 1 position, is also reported. The threshold of this process is calculated to be 17.1 eV. Detailed analysis of ionization products such as in DI is important to trace the sequential steps in the biochemical process of DNA damage.

AUTOBA: automation of backbone assignment from HN(C)N suite of experiments.

Science.gov (United States)

Borkar, Aditi; Kumar, Dinesh; Hosur, Ramakrishna V

2011-07-01

Development of efficient strategies and automation represent important milestones of progress in rapid structure determination efforts in proteomics research. In this context, we present here an efficient algorithm named as AUTOBA (Automatic Backbone Assignment) designed to automate the assignment protocol based on HN(C)N suite of experiments. Depending upon the spectral dispersion, the user can record 2D or 3D versions of the experiments for assignment. The algorithm uses as inputs: (i) protein primary sequence and (ii) peak-lists from user defined HN(C)N suite of experiments. In the end, one gets H(N), (15)N, C(α) and C' assignments (in common BMRB format) for the individual residues along the polypeptide chain. The success of the algorithm has been demonstrated, not only with experimental spectra recorded on two small globular proteins: ubiquitin (76 aa) and M-crystallin (85 aa), but also with simulated spectra of 27 other proteins using assignment data from the BMRB.

Inferential backbone assignment for sparse data

International Nuclear Information System (INIS)

Vitek, Olga; Bailey-Kellogg, Chris; Craig, Bruce; Vitek, Jan

2006-01-01

This paper develops an approach to protein backbone NMR assignment that effectively assigns large proteins while using limited sets of triple-resonance experiments. Our approach handles proteins with large fractions of missing data and many ambiguous pairs of pseudoresidues, and provides a statistical assessment of confidence in global and position-specific assignments. The approach is tested on an extensive set of experimental and synthetic data of up to 723 residues, with match tolerances of up to 0.5 ppm for C α and C β resonance types. The tests show that the approach is particularly helpful when data contain experimental noise and require large match tolerances. The keys to the approach are an empirical Bayesian probability model that rigorously accounts for uncertainty in the data at all stages in the analysis, and a hybrid stochastic tree-based search algorithm that effectively explores the large space of possible assignments

First-line HIV treatment: evaluation of backbone choice and its budget impact

Directory of Open Access Journals (Sweden)

Orietta Zaniolo

2013-06-01

Full Text Available OBJECTIVE: The gradual increase of persons living with HIV, mainly due to the reduced mortality achieved with effective antiretroviral therapies, calls for increased rationality and awareness in health resources consumption also during the early illness phases. Aim of this work is the estimation of the budget impact related to the variation in backbone prescribing trends in naïve patients.METHODS: Target population is the number of patients starting antiretroviral therapy each year, according to the Italian HIV surveillance registry, excluding patients receiving non-authorized or non-recommended regimens. We modeled 3-year mortality and durability rates on a dynamic cohort, basing on international literature. A prevalent patients analysis has also been conducted, for which the model is fed by a closed cohort consisting of all the patients without experience of virologic failure. The aim of this collateral analysis is to estimate the difference in current annual expenditures if the past prescription trends for patients starting therapy would have led to the evaluated hypothetical scenarios. Current Italian market shares of triple regimens containing first-choice or alternative backbones (tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine are compared to three hypothetical scenarios (base-case, minimum and maximum in which increasing shares of patients eligible to abacavir/lamivudine start first line treatment with this backbone. Annual cost for each regimen comprises drugs acquisition under hospital pricing rules, monitoring exams and preventive tests, valued basing on regional reimbursement tariffs.RESULTS: According to current prescribing trends, in the next three years about 13,000 patients starting HIV therapy will receive tenofovir/emtricitabine (83% of the target population, and minor portions other regimens (9% abacavir/lamivudine, 8% zidovudine/lamivudine. Patients that would be eligible to

Integrative technology of massage manipulations in physical rehabilitation of students with backbone pathology

Directory of Open Access Journals (Sweden)

V.I. Kotelevskiy

2016-06-01

Full Text Available Purpose:to analyze effectiveness of massage manipulations’ integrative technology in physical rehabilitation of higher educational establishments’ students with backbone pathology. Material: in the research 195 students of 19-20 years’ age participated. All students had periodical initial neurological symptoms of functional pathology and first stage osteochondrosis in different parts of backbone. We conducted a course of 10 sessions of therapeutic massage. Results: the sense of massage integrative technology is that every specialist shall have certain optimal set of skills and knowledge in technique of manipulation sessions of massage. Integrative technology of massage manipulations consists of psycho-corrective and manipulation parts. It considers psycho-somatic, mechanical and reflex rehabilitation aspects of patho-genesis of backbone functional disorders and vertebral osteochondrosis. Conclusions: depending on pathological process or backbone functional state of every person (peculiarities of his (her psycho-somatic status or, even, his (her bents. Individual approach in choice of strategy, tactic and methodological provisioning of massage session shall be used.

High-Throughput Sequencing Based Methods of RNA Structure Investigation

DEFF Research Database (Denmark)

Kielpinski, Lukasz Jan

In this thesis we describe the development of four related methods for RNA structure probing that utilize massive parallel sequencing. Using them, we were able to gather structural data for multiple, long molecules simultaneously. First, we have established an easy to follow experimental...... and computational protocol for detecting the reverse transcription termination sites (RTTS-Seq). This protocol was subsequently applied to hydroxyl radical footprinting of three dimensional RNA structures to give a probing signal that correlates well with the RNA backbone solvent accessibility. Moreover, we applied...

Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone

OpenAIRE

Nougairede, Antoine; Klitting, Raphaelle; Aubry, Fabien; Gilles, Magali; Touret, Franck; De Lamballerie, Xavier

2018-01-01

Zika virus (ZIKV) recently dispersed throughout the tropics and sub-tropics causing epidemics associated with congenital disease and neurological complications. There is currently no commercial vaccine for ZIKV. Here we describe the initial development of a chimeric virus containing the prM/E proteins of a ZIKV epidemic strain incorporated into a yellow fever 17-D attenuated backbone. Using the versatile and rapid ISA (Infectious Subgenomic Amplicons) reverse genetics method, we compared diff...

Selective backbone labelling of ILV methyl labelled proteins

International Nuclear Information System (INIS)

Sibille, Nathalie; Hanoulle, Xavier; Bonachera, Fanny; Verdegem, Dries; Landrieu, Isabelle; Wieruszeski, Jean-Michel; Lippens, Guy

2009-01-01

Adding the 13 C labelled 2-keto-isovalerate and 2-oxobutanoate precursors to a minimal medium composed of 12 C labelled glucose instead of the commonly used ( 2 D, 13 C) glucose leads not only to the 13 C labelling of (I, L, V) methyls but also to the selective 13 C labelling of the backbone C α and CO carbons of the Ile and Val residues. As a result, the backbone ( 1 H, 15 N) correlations of the Ile and Val residues and their next neighbours in the (i + 1) position can be selectively identified in HN(CA) and HN(CO) planes. The availability of a selective HSQC spectrum corresponding to the sole amide resonances of the Ile and Val residues allows connecting them to their corresponding methyls by the intra-residue NOE effect, and should therefore be applicable to larger systems

Gas separation performance of 6FDA-based polyimides with different chemical structures

KAUST Repository

Qiu, Wulin; Xu, Liren; Chen, Chien-Chiang; Paul, Donald R.; Koros, William J.

2013-01-01

stability of the polyimides membranes relevant to natural gas purification. The consideration of the other gases (He, O2 and N2) provided additional insights regarding effects of backbone structure on detailed penetrant properties. The polyimides studied

Backbone of complex networks of corporations: The flow of control

Science.gov (United States)

Glattfelder, J. B.; Battiston, S.

2009-09-01

We present a methodology to extract the backbone of complex networks based on the weight and direction of links, as well as on nontopological properties of nodes. We show how the methodology can be applied in general to networks in which mass or energy is flowing along the links. In particular, the procedure enables us to address important questions in economics, namely, how control and wealth are structured and concentrated across national markets. We report on the first cross-country investigation of ownership networks, focusing on the stock markets of 48 countries around the world. On the one hand, our analysis confirms results expected on the basis of the literature on corporate control, namely, that in Anglo-Saxon countries control tends to be dispersed among numerous shareholders. On the other hand, it also reveals that in the same countries, control is found to be highly concentrated at the global level, namely, lying in the hands of very few important shareholders. Interestingly, the exact opposite is observed for European countries. These results have previously not been reported as they are not observable without the kind of network analysis developed here.

Molecular data for a biochemical model of DNA damage: Electron impact ionization and dissociative ionization cross sections of DNA bases and sugar-phosphate backbone

International Nuclear Information System (INIS)

Huo, Winifred M.; Dateo, Christopher E.; Fletcher, Graham D.

2006-01-01

As part of the database for building up a biochemical model of DNA radiation damage, electron impact ionization cross sections of sugar-phosphate backbone and DNA bases have been calculated using the improved binary-encounter dipole (iBED) model. It is found that the total ionization cross sections of C 3 ' - and C 5 ' -deoxyribose-phosphate, two conformers of the sugar-phosphate backbone, are close to each other. Furthermore, the sum of the ionization cross sections of the separate deoxyribose and phosphate fragments is in close agreement with the C 3 ' - and C 5 ' -deoxyribose-phosphate cross sections, differing by less than 10%, an indication that a building-up principle may be applicable. Of the four DNA bases, the ionization cross section of guanine is the largest, then in decreasing order, adenine, thymine, and cytosine. The order is in accordance with the known propensity of oxidation of the bases by ionizing radiation. Dissociative ionization (DI), a process that both ionizes and dissociates a molecule, is investigated for cytosine. The DI cross section for the formation of H and (cytosine-H1) + , with the cytosine ion losing H at the 1 position, is also reported. The threshold of this process is calculated to be 16.9eV. Detailed analysis of ionization products such as in DI is important to trace the sequential steps in the biochemical process of DNA damage

Generation of marker- and/or backbone-free transgenic wheat plants via Agrobacterium-mediated transformation

Directory of Open Access Journals (Sweden)

Wang Genping

2016-09-01

Full Text Available Horizontal transfer of antibiotic resistance genes to animals and vertical transfer of herbicide resistance genes to the weedy relatives are perceived as major biosafety concerns in genetically modified (GM crops. In this study, five novel vectors which used gusA and bar as a reporter gene and a selection marker gene, respectively, were constructed based on the pCLEAN dual binary vector system. Among these vectors, 1G7B and 5G7B carried two T-DNAs located on two respective plasmids with 5G7B possessing an additional virGwt gene. 5LBTG154 and 5TGTB154 carried two T-DNAs in the target plasmid with either one or double right borders, and 5BTG154 carried the selectable marker gene on the backbone outside of the T-DNA left border in the target plasmid. In addition, 5BTG154, 5LBTG154 and 5TGTB154 used pAL154 as a helper plasmid which contains Komari fragment to facilitate transformation. These five dual binary vector combinations were transformed into Agrobacterium strain AGL1 and used to transform durum wheat cv Stewart 63. Evaluation of the co-transformation efficiencies, the frequencies of marker-free transgenic plants and integration of backbone sequences in the obtained transgenic lines indicated that two vectors (5G7B and 5TGTB154 were more efficient in generating marker-free transgenic wheat plants with no or minimal integration of backbone sequences in the wheat genome. The vector series developed in this study for generation of marker- and/or backbone-free transgenic wheat plants via Agrobacterium-mediated transformation will be useful to facilitate the creation of ‘clean’ GM wheat containing only the foreign genes of agronomic importance.

Generation of Marker- and/or Backbone-Free Transgenic Wheat Plants via Agrobacterium-Mediated Transformation.

Science.gov (United States)

Wang, Gen-Ping; Yu, Xiu-Dao; Sun, Yong-Wei; Jones, Huw D; Xia, Lan-Qin

2016-01-01

Horizontal transfer of antibiotic resistance genes to animals and vertical transfer of herbicide resistance genes to the weedy relatives are perceived as major biosafety concerns in genetically modified (GM) crops. In this study, five novel vectors which used gusA and bar as a reporter gene and a selection marker gene, respectively, were constructed based on the pCLEAN dual binary vector system. Among these vectors, 1G7B and 5G7B carried two T-DNAs located on two respective plasmids with 5G7B possessing an additional virGwt gene. 5LBTG154 and 5TGTB154 carried two T-DNAs in the target plasmid with either one or double right borders, and 5BTG154 carried the selectable marker gene on the backbone outside of the T-DNA left border in the target plasmid. In addition, 5BTG154, 5LBTG154, and 5TGTB154 used pAL154 as a helper plasmid which contains Komari fragment to facilitate transformation. These five dual binary vector combinations were transformed into Agrobacterium strain AGL1 and used to transform durum wheat cv Stewart 63. Evaluation of the co-transformation efficiencies, the frequencies of marker-free transgenic plants, and integration of backbone sequences in the obtained transgenic lines indicated that two vectors (5G7B and 5TGTB154) were more efficient in generating marker-free transgenic wheat plants with no or minimal integration of backbone sequences in the wheat genome. The vector series developed in this study for generation of marker- and/or backbone-free transgenic wheat plants via Agrobacterium -mediated transformation will be useful to facilitate the creation of "clean" GM wheat containing only the foreign genes of agronomic importance.

Accurate protein structure modeling using sparse NMR data and homologous structure information.

Science.gov (United States)

Thompson, James M; Sgourakis, Nikolaos G; Liu, Gaohua; Rossi, Paolo; Tang, Yuefeng; Mills, Jeffrey L; Szyperski, Thomas; Montelione, Gaetano T; Baker, David

2012-06-19

While information from homologous structures plays a central role in X-ray structure determination by molecular replacement, such information is rarely used in NMR structure determination because it can be incorrect, both locally and globally, when evolutionary relationships are inferred incorrectly or there has been considerable evolutionary structural divergence. Here we describe a method that allows robust modeling of protein structures of up to 225 residues by combining (1)H(N), (13)C, and (15)N backbone and (13)Cβ chemical shift data, distance restraints derived from homologous structures, and a physically realistic all-atom energy function. Accurate models are distinguished from inaccurate models generated using incorrect sequence alignments by requiring that (i) the all-atom energies of models generated using the restraints are lower than models generated in unrestrained calculations and (ii) the low-energy structures converge to within 2.0 Å backbone rmsd over 75% of the protein. Benchmark calculations on known structures and blind targets show that the method can accurately model protein structures, even with very remote homology information, to a backbone rmsd of 1.2-1.9 Å relative to the conventional determined NMR ensembles and of 0.9-1.6 Å relative to X-ray structures for well-defined regions of the protein structures. This approach facilitates the accurate modeling of protein structures using backbone chemical shift data without need for side-chain resonance assignments and extensive analysis of NOESY cross-peak assignments.

Quantification of protein backbone hydrogen-deuterium exchange rates by solid state NMR spectroscopy

International Nuclear Information System (INIS)

Lopez del Amo, Juan-Miguel; Fink, Uwe; Reif, Bernd

2010-01-01

We present the quantification of backbone amide hydrogen-deuterium exchange rates (HDX) for immobilized proteins. The experiments make use of the deuterium isotope effect on the amide nitrogen chemical shift, as well as on proton dilution by deuteration. We find that backbone amides in the microcrystalline α-spectrin SH3 domain exchange rather slowly with the solvent (with exchange rates negligible within the individual 15 N-T 1 timescales). We observed chemical exchange for 6 residues with HDX exchange rates in the range from 0.2 to 5 s -1 . Backbone amide 15 N longitudinal relaxation times that we determined previously are not significantly affected for most residues, yielding no systematic artifacts upon quantification of backbone dynamics (Chevelkov et al. 2008b). Significant exchange was observed for the backbone amides of R21, S36 and K60, as well as for the sidechain amides of N38, N35 and for W41ε. These residues could not be fit in our previous motional analysis, demonstrating that amide proton chemical exchange needs to be considered in the analysis of protein dynamics in the solid-state, in case D 2 O is employed as a solvent for sample preparation. Due to the intrinsically long 15 N relaxation times in the solid-state, the approach proposed here can expand the range of accessible HDX rates in the intermediate regime that is not accessible so far with exchange quench and MEXICO type experiments.

On topological RNA interaction structures.

Science.gov (United States)

Qin, Jing; Reidys, Christian M

2013-07-01

Recently a folding algorithm of topological RNA pseudoknot structures was presented in Reidys et al. (2011). This algorithm folds single-stranded γ-structures, that is, RNA structures composed by distinct motifs of bounded topological genus. In this article, we set the theoretical foundations for the folding of the two backbone analogues of γ structures: the RNA γ-interaction structures. These are RNA-RNA interaction structures that are constructed by a finite number of building blocks over two backbones having genus at most γ. Combinatorial properties of γ-interaction structures are of practical interest since they have direct implications for the folding of topological interaction structures. We compute the generating function of γ-interaction structures and show that it is algebraic, which implies that the numbers of interaction structures can be computed recursively. We obtain simple asymptotic formulas for 0- and 1-interaction structures. The simplest class of interaction structures are the 0-interaction structures, which represent the two backbone analogues of secondary structures.

Detection of closed influenza virus hemagglutinin fusion peptide structures in membranes by backbone {sup 13}CO-{sup 15}N rotational-echo double-resonance solid-state NMR

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Ujjayini; Xie Li; Weliky, David P., E-mail: weliky@chemistry.msu.edu [Michigan State University, Department of Chemistry (United States)

2013-02-15

The influenza virus fusion peptide is the N-terminal {approx}20 residues of the HA2 subunit of the hemagglutinin protein and this peptide plays a key role in the fusion of the viral and endosomal membranes during initial infection of a cell. The fusion peptide adopts N-helix/turn/C-helix structure in both detergent and membranes with reports of both open and closed interhelical topologies. In the present study, backbone {sup 13}CO-{sup 15}N REDOR solid-state NMR was applied to the membrane-associated fusion peptide to detect the distribution of interhelical distances. The data clearly showed a large fraction of closed and semi-closed topologies and were best-fitted to a mixture of two structures that do not exchange. One of the earlier open structural models may have incorrect G13 dihedral angles derived from TALOS analysis of experimentally correct {sup 13}C shifts.

Sulfation and cation effects on the conformational properties of the glycan backbone of chondroitin sulfate disaccharides.

Science.gov (United States)

Faller, Christina E; Guvench, Olgun

2015-05-21

Chondroitin sulfate (CS) is one of several glycosaminoglycans that are major components of proteoglycans. A linear polymer consisting of repeats of the disaccharide -4GlcAβ1-3GalNAcβ1-, CS undergoes differential sulfation resulting in five unique sulfation patterns. Because of the dimer repeat, the CS glycosidic "backbone" has two distinct sets of conformational degrees of freedom defined by pairs of dihedral angles: (ϕ1, ψ1) about the β1-3 glycosidic linkage and (ϕ2, ψ2) about the β1-4 glycosidic linkage. Differential sulfation and the possibility of cation binding, combined with the conformational flexibility and biological diversity of CS, complicate experimental efforts to understand CS three-dimensional structures at atomic resolution. Therefore, all-atom explicit-solvent molecular dynamics simulations with Adaptive Biasing Force sampling of the CS backbone were applied to obtain high-resolution, high-precision free energies of CS disaccharides as a function of all possible backbone geometries. All 10 disaccharides (β1-3 vs β1-4 linkage × five different sulfation patterns) were studied; additionally, ion effects were investigated by considering each disaccharide in the presence of either neutralizing sodium or calcium cations. GlcAβ1-3GalNAc disaccharides have a single, broad, thermodynamically important free-energy minimum, whereas GalNAcβ1-4GlcA disaccharides have two such minima. Calcium cations but not sodium cations bind to the disaccharides, and binding is primarily to the GlcA -COO(-) moiety as opposed to sulfate groups. This binding alters the glycan backbone thermodynamics in instances where a calcium cation bound to -COO(-) can act to bridge and stabilize an interaction with an adjacent sulfate group, whereas, in the absence of this cation, the proximity of a sulfate group to -COO(-) results in two like charges being both desolvated and placed adjacent to each other and is found to be destabilizing. In addition to providing information

Instant Backbone.js application development

CERN Document Server

Hunter, Thomas

2013-01-01

Get to grips with a new technology, understand what it is and what it can do for you, and then get to work with the most important features and tasks. This book is a practical, step-by-step tutorial that will teach you to build Backbone.js applications quickly and efficiently.This book is targeted towards developers. It is assumed that you have at least a basic understanding of JavaScript and jQuery selectors. If you are interested in building dynamic Single Page Applications that interact heavily with a backend server, then this is the book for you.

Nuclear Magnetic Resonance-Based Structural Characterization and Backbone Dynamics of Recombinant Bee Venom Melittin.

Science.gov (United States)

Ramirez, Lisa; Shekhtman, Alexander; Pande, Jayanti

2018-04-30

In recent years, there has been a resurgence of interest in melittin and its variants as their therapeutic potential has become increasingly evident. Melittin is a 26-residue peptide and a toxic component of honey bee venom. The versatility of melittin in interacting with various biological substrates, such as membranes, glycosaminoglycans, and a variety of proteins, has inspired a slew of studies that aim to improve our understanding of the structural basis of such interactions. However, these studies have largely focused on melittin solutions at high concentrations (>1 mM), even though melittin is generally effective at lower (micromolar) concentrations. Here we present high-resolution nuclear magnetic resonance studies in the lower-concentration regime using a novel method to produce isotope-labeled ( 15 N and 13 C) recombinant melittin. We provide residue-specific structural characterization of melittin in dilute aqueous solution and in 2,2,2-trifluoroethanol/water mixtures, which mimic melittin structure-function and interactions in aqueous and membrane-like environments, respectively. We find that the cis-trans isomerization of Pro14 is key to changes in the secondary structure of melittin. Thus, this study provides residue-specific structural information about melittin in the free state and in a model of the substrate-bound state. These results, taken together with published work from other laboratories, reveal the peptide's structural versatility that resembles that of intrinsically disordered proteins and peptides.

Pemetrexed With Platinum Combination as a Backbone for Targeted Therapy in Non-Small-Cell Lung Cancer.

Science.gov (United States)

Stinchcombe, Thomas E; Borghaei, Hossein; Barker, Scott S; Treat, Joseph Anthony; Obasaju, Coleman

2016-01-01

Standard platinum-based chemotherapy combinations for advanced non-small-cell lung cancer (NSCLC) have reached a plateau in terms of the survival benefit they offer for patients. In addition, the emerging clinical trend of tailored treatment based on patient characteristics has led to the development of therapeutic strategies that target specific cancer-related molecular pathways, including epidermal growth factor receptor (EGFR), angiogenesis, and anaplastic lymphoma kinase inhibitors. Current research is focused on combining targeted therapy with platinum-based chemotherapy in an endeavor to achieve an additional benefit in specific patient populations. Currently, pemetrexed is indicated for use in the first-line, maintenance, and second-line settings for the treatment of nonsquamous NSCLC. The combination of pemetrexed and cisplatin is well tolerated and is the approved standard first-line therapy. Thus, the pemetrexed-platinum backbone provides an attractive option for combination with targeted therapies. This review aims to summarize the current knowledge and future prospects of the use of pemetrexed-platinum as a backbone for combination with targeted therapies for NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

PASA - A Program for Automated Protein NMR Backbone Signal Assignment by Pattern-Filtering Approach

International Nuclear Information System (INIS)

Xu Yizhuang; Wang Xiaoxia; Yang Jun; Vaynberg, Julia; Qin Jun

2006-01-01

We present a new program, PASA (Program for Automated Sequential Assignment), for assigning protein backbone resonances based on multidimensional heteronuclear NMR data. Distinct from existing programs, PASA emphasizes a per-residue-based pattern-filtering approach during the initial stage of the automated 13 C α and/or 13 C β chemical shift matching. The pattern filter employs one or multiple constraints such as 13 C α /C β chemical shift ranges for different amino acid types and side-chain spin systems, which helps to rule out, in a stepwise fashion, improbable assignments as resulted from resonance degeneracy or missing signals. Such stepwise filtering approach substantially minimizes early false linkage problems that often propagate, amplify, and ultimately cause complication or combinatorial explosion of the automation process. Our program (http://www.lerner.ccf.org/moleccard/qin/) was tested on four representative small-large sized proteins with various degrees of resonance degeneracy and missing signals, and we show that PASA achieved the assignments efficiently and rapidly that are fully consistent with those obtained by laborious manual protocols. The results demonstrate that PASA may be a valuable tool for NMR-based structural analyses, genomics, and proteomics

Performance of Flow-Aware Networking in LTE backbone

DEFF Research Database (Denmark)

Sniady, Aleksander; Soler, José

2012-01-01

technologies, such as Long Term Evolution (LTE). This paper proposes usage of a modified Flow Aware Networking (FAN) technique for enhancing Quality of Service (QoS) in the all-IP transport networks underlying LTE backbone. The results obtained with OPNET Modeler show that FAN, in spite of being relatively...

Capturing non-local interactions by long short-term memory bidirectional recurrent neural networks for improving prediction of protein secondary structure, backbone angles, contact numbers and solvent accessibility.

Science.gov (United States)

Heffernan, Rhys; Yang, Yuedong; Paliwal, Kuldip; Zhou, Yaoqi

2017-09-15

The accuracy of predicting protein local and global structural properties such as secondary structure and solvent accessible surface area has been stagnant for many years because of the challenge of accounting for non-local interactions between amino acid residues that are close in three-dimensional structural space but far from each other in their sequence positions. All existing machine-learning techniques relied on a sliding window of 10-20 amino acid residues to capture some 'short to intermediate' non-local interactions. Here, we employed Long Short-Term Memory (LSTM) Bidirectional Recurrent Neural Networks (BRNNs) which are capable of capturing long range interactions without using a window. We showed that the application of LSTM-BRNN to the prediction of protein structural properties makes the most significant improvement for residues with the most long-range contacts (|i-j| >19) over a previous window-based, deep-learning method SPIDER2. Capturing long-range interactions allows the accuracy of three-state secondary structure prediction to reach 84% and the correlation coefficient between predicted and actual solvent accessible surface areas to reach 0.80, plus a reduction of 5%, 10%, 5% and 10% in the mean absolute error for backbone ϕ , ψ , θ and τ angles, respectively, from SPIDER2. More significantly, 27% of 182724 40-residue models directly constructed from predicted C α atom-based θ and τ have similar structures to their corresponding native structures (6Å RMSD or less), which is 3% better than models built by ϕ and ψ angles. We expect the method to be useful for assisting protein structure and function prediction. The method is available as a SPIDER3 server and standalone package at http://sparks-lab.org . yaoqi.zhou@griffith.edu.au or yuedong.yang@griffith.edu.au. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email

CheShift-2 resolves a local inconsistency between two X-ray crystal structures

International Nuclear Information System (INIS)

Vila, Jorge A.; Sue, Shih-Che; Fraser, James S.; Scheraga, Harold A.; Dyson, H. Jane

2012-01-01

Since chemical shifts provide important and relatively accessible information about protein structure in solution, a Web server, CheShift-2, was developed for structure interrogation, based on a quantum mechanics database of 13 C α chemical shifts. We report the application of CheShift-2 to a local inconsistency between two X-ray crystal structures (PDB IDs 1IKN and 1NFI) of the complex between the p65/p50 heterodimer of NFκB and its inhibitor IκBα. The availability of NMR resonance assignments that included the region of the inconsistency provided an opportunity for independent validation of the CheShift-2 server. Application of the server showed that the 13 C α chemical shifts measured for the Gly270-Pro281 sequence close to the C-terminus of IκBα were unequivocally consistent with the backbone structure modeled in the 1IKN structure, and were inconsistent with the 1NFI structure. Previous NOE measurements had demonstrated that the position of a tryptophan ring in the region immediately N-terminal in this region was not consistent with either structure. Subsequent recalculation of the local structure in this region, based on the electron density of the deposited structure factors for 1IKN, confirmed that the local backbone structure was best modeled by 1IKN, but that the rotamer of Trp258 is consistent with the 1NFI structure, including the presence of a hydrogen bond between the ring NεH of Trp258 and the backbone carbonyl group of Gln278. The consensus between all of these measures suggests that the CheShift-2 server operates well under circumstances in which backbone chemical shifts are available but where local plasticity may render X-ray structural data ambiguous.

(1)H, (13)C, and (15)N backbone resonance assignments of the full-length 40 kDa S. acidocaldarius Y-family DNA polymerase, dinB homolog.

Science.gov (United States)

Moro, Sean L; Cocco, Melanie J

2015-10-01

The dinB homolog (Dbh) is a member of the Y-family of translesion DNA polymerases, which are specialized to accurately replicate DNA across from a wide variety of lesions in living cells. Lesioned bases block the progression of high-fidelity polymerases and cause detrimental replication fork stalling; Y-family polymerases can bypass these lesions. The active site of the translesion synthesis polymerase is more open than that of a replicative polymerase; consequently Dbh polymerizes with low fidelity. Bypass polymerases also have low processivity. Short extension past the lesion allows the high-fidelity polymerase to switch back onto the site of replication. Dbh and the other Y-family polymerases have been used as structural models to investigate the mechanisms of DNA polymerization and lesion bypass. Many high-resolution crystal structures of Y-family polymerases have been reported. NMR dynamics studies can complement these structures by providing a measure of protein motions. Here we report the (15)N, (1)H, and (13)C backbone resonance assignments at two temperatures (35 and 50 °C) for Sulfolobus acidocaldarius Dbh polymerase. Backbone resonance assignments have been obtained for 86 % of the residues. The polymerase active site is assigned as well as the majority of residues in each of the four domains.

Towards a natural classification and backbone tree for Sordariomycete

Digital Repository Service at National Institute of Oceanography (India)

Maharachchikumbura, S.S.N.; Hyde, K.D.; Jones, E.B.G.; McKenzie, E.H.C.; Huang, S.-K.; Abdel-Wahab, M.A.; Daranagama, D.A.; Dayarathne, M.; D'souza, M.J.; Goonasekara, I.D.; Hongsanan, S.; Jayawardena, R.S.; Kirk, P.M.; Konta, S.; Liu, J.-K.; Liu, Z.-Y.; Norphanphoun, C.; Pang, K.-L.; Perera, R.H.; Senanayake, I.C.; Shang, Q.; Shenoy, B.D.; Xiao, Y.; Bahkali, A.H.; Kang, J.; Somrothipol, S.; Suetrong, S.; Wen, T.; Xu, J.

, lichenized or lichenicolous taxa The class includes freshwater, marine and terrestrial taxa and has a worldwide distribution This paper provides an updated outline of the Sordariomycetes and a backbone tree incorporating asexual and sexual genera in the class...

Backbone dynamics of oxidized and reduced D. vulgaris flavodoxin in solution

International Nuclear Information System (INIS)

Hrovat, Andrea; Bluemel, Markus; Loehr, Frank; Mayhew, Stephen G.; Rueterjans, Heinz

1997-01-01

Recombinant Desulfovibrio vulgaris flavodoxin was produced in Escherichia coli. A complete backbone NMR assignment for the two-electron reduced protein revealed significant changes of chemical shift values compared to the oxidized protein, in particular for the flavine mononucleotide (FMN)-binding site. A comparison of homo- and heteronuclear NOESY spectra for the two redox states led to the assumption that reduction is not accompanied by significant changes of the global fold of the protein.The backbone dynamics of both the oxidized and reduced forms of D. vulgaris flavodoxin were investigated using two-dimensional 15 N- 1 H correlation NMR spectroscopy.T 1 , T 2 and NOE data are obtained for 95% of the backbone amide groups in both redox states. These values were analysed in terms of the 'model-free' approach introduced by Lipari and Szabo [(1982) J. Am. Chem. Soc., 104, 4546-;4559, 4559-;4570]. A comparison of the two redox states indicates that in the reduced species significantly more flexibility occurs in the two loop regions enclosing FMN.Also, a higher amplitude of local motion could be found for the N(3)H group of FMN bound to the reduced protein compared to the oxidized state

PPM-One: a static protein structure based chemical shift predictor

International Nuclear Information System (INIS)

Li, Dawei; Brüschweiler, Rafael

2015-01-01

We mined the most recent editions of the BioMagResDataBank and the protein data bank to parametrize a new empirical knowledge-based chemical shift predictor of protein backbone atoms using either a linear or an artificial neural network model. The resulting chemical shift predictor PPM-One accepts a single static 3D structure as input and emulates the effect of local protein dynamics via interatomic steric contacts. Furthermore, the chemical shift prediction was extended to most side-chain protons and it is found that the prediction accuracy is at a level allowing an independent assessment of stereospecific assignments. For a previously established set of test proteins some overall improvement was achieved over current top-performing chemical shift prediction programs

New theories for smectic and nematic liquid-crystal polymers: Backbone LCPs [liquid crystalline polymers] and their mixtures and side-chain LCPs

International Nuclear Information System (INIS)

Dowell, F.

1987-01-01

A summary of predictions and explanations from statistical-physics theories for both backbone and side-chain liquid crystalline polymers (LCPs) and for mixtures with backbone LCPs are presented. Trends in the thermodynamic and molecular ordering properties have been calculated as a function of pressure, density, temperature, and molecule chemical structures (including degree of polymerization and the following properties of the chemical structures of the repeat units: lengths and shapes, intra-chain rotation energies, dipole moments, site-site polarizabilities and Lennard-Jones potentials, etc.) in nematic and multiple smectic-A LC phases and in the isotropic liquid phase. The theoretical results are found to be in good agreement with existing experimental data. These theories can also be applied to combined LCPs. Since these theories have no ad hoc or arbitrarily adjustable parameters, these theories can be used to design new LCPs and new solvents as well as to predict and explain properties. 27 refs., 4 tabs

Network Traffic Prediction Based on Deep Belief Network and Spatiotemporal Compressive Sensing in Wireless Mesh Backbone Networks

Directory of Open Access Journals (Sweden)

Laisen Nie

2018-01-01

Full Text Available Wireless mesh network is prevalent for providing a decentralized access for users and other intelligent devices. Meanwhile, it can be employed as the infrastructure of the last few miles connectivity for various network applications, for example, Internet of Things (IoT and mobile networks. For a wireless mesh backbone network, it has obtained extensive attention because of its large capacity and low cost. Network traffic prediction is important for network planning and routing configurations that are implemented to improve the quality of service for users. This paper proposes a network traffic prediction method based on a deep learning architecture and the Spatiotemporal Compressive Sensing method. The proposed method first adopts discrete wavelet transform to extract the low-pass component of network traffic that describes the long-range dependence of itself. Then, a prediction model is built by learning a deep architecture based on the deep belief network from the extracted low-pass component. Otherwise, for the remaining high-pass component that expresses the gusty and irregular fluctuations of network traffic, the Spatiotemporal Compressive Sensing method is adopted to predict it. Based on the predictors of two components, we can obtain a predictor of network traffic. From the simulation, the proposed prediction method outperforms three existing methods.

Backbone assignment of the little finger domain of a Y-family DNA polymerase.

Science.gov (United States)

Ma, Dejian; Fowler, Jason D; Suo, Zucai

2011-10-01

Sulfolobus solfataricus DNA polymerase IV (Dpo4), a prototype Y-family DNA polymerase, contains a unique little finger domain besides a catalytic core. Here, we report the chemical shift assignments for the backbone nitrogens, α and β carbons, and amide protons of the little finger domain of Dpo4. This work and our published backbone assignment for the catalytic core provide the basis for investigating the conformational dynamics of Dpo4 during catalysis using solution NMR spectroscopy.

(nBuCp)2ZrCl2-catalyzed Ethylene-4M1P Copolymerization: Copolymer Backbone Structure, Melt Behavior, and Crystallization

KAUST Repository

Atiqullah, Muhammad

2016-01-08

The judicious design of methylaluminoxane (MAO) anions expands the scope for developing industrial metallocene catalysts. Therefore, the effects of MAO anion design on the backbone structure, melt behavior, and crystallization of ethylene−4-methyl-1-pentene (E−4M1P) copolymer were investigated. Ethylene was homopolymerized, as well as copolymerized with 4M1P, using (i) MAO anion A (unsupported [MAOCl2]−) premixed with dehydroxylated silica, (nBuCp)2ZrCl2, and Me2SiCl2; and (ii) MAO anion B (Si−O−Me2Si−[MAOCl2]−) supported with (nBuCp)2ZrCl2 on Me2SiCl2-functionalized silica. Unsupported Me2SiCl2, opposite to the supported analogue, acted as a co-chain transfer agent with 4M1P. The modeling of polyethylene melting and crystallization kinetics, including critical crystallite stability, produced insightful results. This study especially illustrates how branched polyethylene can be prepared from ethylene alone using particularly one metallocene-MAO ion pair, and how a compound, that functionalizes silica as well as terminates the chain, can synthesize ethylene−α-olefin copolymers with novel structures. Hence, it unfolds prospective future research niches in polyethyne systhesis. This article is protected by copyright. All rights reserved.

Receptor structure-based discovery of non-metabolite agonists for the succinate receptor GPR91

DEFF Research Database (Denmark)

Trauelsen, Mette; Rexen Ulven, Elisabeth; Hjorth, Siv A

2017-01-01

therefore binds in a very different mode than generally believed. Importantly, an empty side-pocket is identified next to the succinate binding site. All this information formed the basis for a substructure-based search query, which, combined with molecular docking, was used in virtual screening of the ZINC...... database to pick two serial mini-libraries of a total of only 245 compounds from which sub-micromolar, selective GPR91 agonists of unique structures were identified. The best compounds were backbone-modified succinate analogs in which an amide-linked hydrophobic moiety docked into the side-pocket next...

Wetting of nonconserved residue-backbones: A feature indicative of aggregation associated regions of proteins.

Science.gov (United States)

Pradhan, Mohan R; Pal, Arumay; Hu, Zhongqiao; Kannan, Srinivasaraghavan; Chee Keong, Kwoh; Lane, David P; Verma, Chandra S

2016-02-01

Aggregation is an irreversible form of protein complexation and often toxic to cells. The process entails partial or major unfolding that is largely driven by hydration. We model the role of hydration in aggregation using "Dehydrons." "Dehydrons" are unsatisfied backbone hydrogen bonds in proteins that seek shielding from water molecules by associating with ligands or proteins. We find that the residues at aggregation interfaces have hydrated backbones, and in contrast to other forms of protein-protein interactions, are under less evolutionary pressure to be conserved. Combining evolutionary conservation of residues and extent of backbone hydration allows us to distinguish regions on proteins associated with aggregation (non-conserved dehydron-residues) from other interaction interfaces (conserved dehydron-residues). This novel feature can complement the existing strategies used to investigate protein aggregation/complexation. © 2015 Wiley Periodicals, Inc.

Molecular couplings and energy exchange between DNA and water mapped by femtosecond infrared spectroscopy of backbone vibrations

Directory of Open Access Journals (Sweden)

Yingliang Liu

2017-07-01

Full Text Available Molecular couplings between DNA and water together with the accompanying processes of energy exchange are mapped via the ultrafast response of DNA backbone vibrations after OH stretch excitation of the water shell. Native salmon testes DNA is studied in femtosecond pump-probe experiments under conditions of full hydration and at a reduced hydration level with two water layers around the double helix. Independent of their local hydration patterns, all backbone vibrations in the frequency range from 940 to 1120 cm–1 display a quasi-instantaneous reshaping of the spectral envelopes of their fundamental absorption bands upon excitation of the water shell. The subsequent reshaping kinetics encompass a one-picosecond component, reflecting the formation of a hot ground state of the water shell, and a slower contribution on a time scale of tens of picoseconds. Such results are benchmarked by measurements with resonant excitation of the backbone modes, resulting in distinctly different absorption changes. We assign the fast changes of DNA absorption after OH stretch excitation to structural changes in the water shell which couple to DNA through the local electric fields. The second slower process is attributed to a flow of excess energy from the water shell into DNA, establishing a common heated ground state in the molecular ensemble. This interpretation is supported by theoretical calculations of the electric fields exerted by the water shell at different temperatures.

Polyolefin backbone substitution in binders for low temperature powder injection moulding feedstocks.

Science.gov (United States)

Hausnerova, Berenika; Kuritka, Ivo; Bleyan, Davit

2014-02-27

This paper reports the substitution of polyolefin backbone binder components with low melting temperature carnauba wax for powder injection moulding applications. The effect of various binder compositions of Al₂O₃ feedstock on thermal degradation parameters is investigated by thermogravimetric analysis. Within the experimental framework 29 original feedstock compositions were prepared and the superiority of carnauba wax over the polyethylene binder backbone was demonstrated in compositions containing polyethylene glycol as the initial opening agent and governing the proper mechanism of the degradation process. Moreover, the replacement of synthetic polymer by the natural wax contributes to an increase of environmental sustainability of modern industrial technologies.

Internet Backbone in the Democratic Republic of Congo : Feasibility ...

International Development Research Centre (IDRC) Digital Library (Canada)

Internet Backbone in the Democratic Republic of Congo : Feasibility Study and Advocacy. During 7-10 February 2005, representatives of five francophone African countries (Cameroon, Morocco, Niger, Sénégal, and the Democratic Republic of Congo - DRC) met to consider ways and means of galvanizing the appropriation ...

Oxidation Responsive Polymers with a Triggered Degradation via Arylboronate Self-Immolative Motifs on a Polyphosphazene Backbone.

Science.gov (United States)

Iturmendi, Aitziber; Monkowius, Uwe; Teasdale, Ian

2017-02-21

Oxidation responsive polymers with triggered degradation pathways have been prepared via attachment of self-immolative moieties onto a hydrolytically unstable polyphosphazene backbone. After controlled main-chain growth, postpolymerization functionalization allows the preparation of hydrolytically stable poly(organo)phosphazenes decorated with a phenylboronic ester caging group. In oxidative environments, triggered cleavage of the caging group is followed by self-immolation, exposing the unstable glycine-substituted polyphosphazene which subsequently undergoes to backbone degradation to low-molecular weight molecules. As well as giving mechanistic insights, detailed GPC and 1 H and 31 P NMR analysis reveal the polymers to be stable in aqueous solutions, but show a selective, fast degradation upon exposure to hydrogen peroxide containing solutions. Since the post-polymerization functionalization route allows simple access to polymer backbones with a broad range of molecular weights, the approach of using the inorganic backbone as a platform significantly expands the toolbox of polymers capable of stimuli-responsive degradation.

Dynamic power control for wireless backbone mesh networks: a survey

CSIR Research Space (South Africa)

Olwal, TO

2010-01-01

Full Text Available points of failures, and robust against RF interference, obstacles or power outage. This is because WMRs forming wireless backbone mesh networks (WBMNs) are built on advanced physical technologies. Such nodes perform both accessing and forwarding...

Rigidity of the polypeptide backbone in the triple-stranded collagen molecule.

Science.gov (United States)

Nemethy, G

1981-02-01

Conformational energy computations were carried out on collagen-like triple-stranded conformations of several polytripeptides with the structure CH3CO(GXY)3NHCH3, where X and Y can be Pro, Ala, or Gly. The computed minimum-energy conformations for various sequences are compared with that computed earlier for poly(Gly-Pro-Pro). Usually, substitution of Ala or Gly residues for Pro does not cause any strain or distortion of the conformation of the triple-stranded complex. Thus, the structure is a very stable and essentially rigid one. Unfavorable interactions were found only in the case of CH3CO(Gly-Ala-Pro)NHCH3. These interactions are a consequence of differences between the residue geometry of Ala and Pro. They result in small changes of some backbone dihedral angles and in an increase of intra- and interchain energies. The presence of a single Gly-Ala-Pro tripeptide within a sequence of Gly-Pro-Pro tripeptides is not sufficient, however, to cause even a small distoration of the triple strand. No deviation of the peptide groups from planarity is required to stabilize the triple-stranded structure.

Structural protein descriptors in 1-dimension and their sequence-based predictions.

Science.gov (United States)

Kurgan, Lukasz; Disfani, Fatemeh Miri

2011-09-01

The last few decades observed an increasing interest in development and application of 1-dimensional (1D) descriptors of protein structure. These descriptors project 3D structural features onto 1D strings of residue-wise structural assignments. They cover a wide-range of structural aspects including conformation of the backbone, burying depth/solvent exposure and flexibility of residues, and inter-chain residue-residue contacts. We perform first-of-its-kind comprehensive comparative review of the existing 1D structural descriptors. We define, review and categorize ten structural descriptors and we also describe, summarize and contrast over eighty computational models that are used to predict these descriptors from the protein sequences. We show that the majority of the recent sequence-based predictors utilize machine learning models, with the most popular being neural networks, support vector machines, hidden Markov models, and support vector and linear regressions. These methods provide high-throughput predictions and most of them are accessible to a non-expert user via web servers and/or stand-alone software packages. We empirically evaluate several recent sequence-based predictors of secondary structure, disorder, and solvent accessibility descriptors using a benchmark set based on CASP8 targets. Our analysis shows that the secondary structure can be predicted with over 80% accuracy and segment overlap (SOV), disorder with over 0.9 AUC, 0.6 Matthews Correlation Coefficient (MCC), and 75% SOV, and relative solvent accessibility with PCC of 0.7 and MCC of 0.6 (0.86 when homology is used). We demonstrate that the secondary structure predicted from sequence without the use of homology modeling is as good as the structure extracted from the 3D folds predicted by top-performing template-based methods.

Suitability assessment of OPC UA as the backbone of ground-based observatory control systems

International Nuclear Information System (INIS)

Pessemier, W.; Raskin, G.; Van Winckel, H.; Deconinck, G.; Saey, P.

2012-01-01

A common requirement of modern observatory control systems is to allow interaction between various heterogeneous subsystems in a transparent way. However, the integration of off-the-shelf (OTS) industrial products - such as Programmable Logic Controllers (PLCs) and Supervisory Control And Data Acquisition (SCADA) software - has long been hampered by the lack of an adequate interfacing method. With the advent of the Unified Architecture (UA) version of OPC (Object Linking and Embedding for Process Control), the limitations of the original industry accepted interface are now lifted, and also much more functionality has been defined. In this paper the most important features of OPC UA are matched against the requirements of ground-based observatory control systems in general and in particular of the 1.2 m Mercator Telescope. We investigate the opportunities of the 'information modelling' idea behind OPC UA, which could allow an extensive standardization in the field of astronomical instrumentation, similar to the efforts emerging in several industry domains. Because OPC UA is designed for both horizontal and vertical integration of heterogeneous subsystems, we explore its capabilities to serve as the backbone of a dependable and scalable observatory control system, treating industrial components like PLCs no differently than custom software components. Performance measurements and tests with a sample of OTS OPC UA products are presented. (authors)

Higher order structural effects stabilizing the reverse watson-crick guanine-cytosine base pair in functional RNAs

KAUST Repository

Chawla, Mohit

2013-10-10

The G:C reverse Watson-Crick (W:W trans) base pair, also known as Levitt base pair in the context of tRNAs, is a structurally and functionally important base pair that contributes to tertiary interactions joining distant domains in functional RNA molecules and also participates in metabolite binding in riboswitches. We previously indicated that the isolated G:C W:W trans base pair is a rather unstable geometry, and that dicationic metal binding to the Guanine base or posttranscriptional modification of the Guanine can increase its stability. Herein, we extend our survey and report on other H-bonding interactions that can increase the stability of this base pair. To this aim, we performed a bioinformatics search of the PDB to locate all the occurencies of G:C trans base pairs. Interestingly, 66% of the G:C trans base pairs in the PDB are engaged in additional H-bonding interactions with other bases, the RNA backbone or structured water molecules. High level quantum mechanical calculations on a data set of representative crystal structures were performed to shed light on the structural stability and energetics of the various crystallographic motifs. This analysis was extended to the binding of the preQ1 metabolite to a preQ1-II riboswitch. 2013 The Author(s).

Towards fully automated structure-based NMR resonance assignment of 15N-labeled proteins from automatically picked peaks

KAUST Repository

Jang, Richard; Gao, Xin; Li, Ming

2011-01-01

In NMR resonance assignment, an indispensable step in NMR protein studies, manually processed peaks from both N-labeled and C-labeled spectra are typically used as inputs. However, the use of homologous structures can allow one to use only N-labeled NMR data and avoid the added expense of using C-labeled data. We propose a novel integer programming framework for structure-based backbone resonance assignment using N-labeled data. The core consists of a pair of integer programming models: one for spin system forming and amino acid typing, and the other for backbone resonance assignment. The goal is to perform the assignment directly from spectra without any manual intervention via automatically picked peaks, which are much noisier than manually picked peaks, so methods must be error-tolerant. In the case of semi-automated/manually processed peak data, we compare our system with the Xiong-Pandurangan-Bailey- Kellogg's contact replacement (CR) method, which is the most error-tolerant method for structure-based resonance assignment. Our system, on average, reduces the error rate of the CR method by five folds on their data set. In addition, by using an iterative algorithm, our system has the added capability of using the NOESY data to correct assignment errors due to errors in predicting the amino acid and secondary structure type of each spin system. On a publicly available data set for human ubiquitin, where the typing accuracy is 83%, we achieve 91% accuracy, compared to the 59% accuracy obtained without correcting for such errors. In the case of automatically picked peaks, using assignment information from yeast ubiquitin, we achieve a fully automatic assignment with 97% accuracy. To our knowledge, this is the first system that can achieve fully automatic structure-based assignment directly from spectra. This has implications in NMR protein mutant studies, where the assignment step is repeated for each mutant. © Copyright 2011, Mary Ann Liebert, Inc.

Towards fully automated structure-based NMR resonance assignment of 15N-labeled proteins from automatically picked peaks

KAUST Repository

Jang, Richard

2011-03-01

In NMR resonance assignment, an indispensable step in NMR protein studies, manually processed peaks from both N-labeled and C-labeled spectra are typically used as inputs. However, the use of homologous structures can allow one to use only N-labeled NMR data and avoid the added expense of using C-labeled data. We propose a novel integer programming framework for structure-based backbone resonance assignment using N-labeled data. The core consists of a pair of integer programming models: one for spin system forming and amino acid typing, and the other for backbone resonance assignment. The goal is to perform the assignment directly from spectra without any manual intervention via automatically picked peaks, which are much noisier than manually picked peaks, so methods must be error-tolerant. In the case of semi-automated/manually processed peak data, we compare our system with the Xiong-Pandurangan-Bailey- Kellogg\\'s contact replacement (CR) method, which is the most error-tolerant method for structure-based resonance assignment. Our system, on average, reduces the error rate of the CR method by five folds on their data set. In addition, by using an iterative algorithm, our system has the added capability of using the NOESY data to correct assignment errors due to errors in predicting the amino acid and secondary structure type of each spin system. On a publicly available data set for human ubiquitin, where the typing accuracy is 83%, we achieve 91% accuracy, compared to the 59% accuracy obtained without correcting for such errors. In the case of automatically picked peaks, using assignment information from yeast ubiquitin, we achieve a fully automatic assignment with 97% accuracy. To our knowledge, this is the first system that can achieve fully automatic structure-based assignment directly from spectra. This has implications in NMR protein mutant studies, where the assignment step is repeated for each mutant. © Copyright 2011, Mary Ann Liebert, Inc.

Polyolefin Backbone Substitution in Binders for Low Temperature Powder Injection Moulding Feedstocks

Directory of Open Access Journals (Sweden)

Berenika Hausnerova

2014-02-01

Full Text Available This paper reports the substitution of polyolefin backbone binder components with low melting temperature carnauba wax for powder injection moulding applications. The effect of various binder compositions of Al2O3 feedstock on thermal degradation parameters is investigated by thermogravimetric analysis. Within the experimental framework 29 original feedstock compositions were prepared and the superiority of carnauba wax over the polyethylene binder backbone was demonstrated in compositions containing polyethylene glycol as the initial opening agent and governing the proper mechanism of the degradation process. Moreover, the replacement of synthetic polymer by the natural wax contributes to an increase of environmental sustainability of modern industrial technologies.

“Pinning strategy”: a novel approach for predicting the backbone ...

Indian Academy of Sciences (India)

Prakash

To assess the quality of the strategy, we define two measures. The first one ...... modular framework of the protein backbone; Protein Eng. 12. 1063–1073 .... Richardson J S, Getzoff E D and Richardson D C 1978 The beta bulge: a common ...

4D experiments measured with APSY for automated backbone resonance assignments of large proteins

International Nuclear Information System (INIS)

Krähenbühl, Barbara; Boudet, Julien; Wider, Gerhard

2013-01-01

Detailed structural and functional characterization of proteins by solution NMR requires sequence-specific resonance assignment. We present a set of transverse relaxation optimization (TROSY) based four-dimensional automated projection spectroscopy (APSY) experiments which are designed for resonance assignments of proteins with a size up to 40 kDa, namely HNCACO, HNCOCA, HNCACB and HN(CO)CACB. These higher-dimensional experiments include several sensitivity-optimizing features such as multiple quantum parallel evolution in a ‘just-in-time’ manner, aliased off-resonance evolution, evolution-time optimized APSY acquisition, selective water-handling and TROSY. The experiments were acquired within the concept of APSY, but they can also be used within the framework of sparsely sampled experiments. The multidimensional peak lists derived with APSY provided chemical shifts with an approximately 20 times higher precision than conventional methods usually do, and allowed the assignment of 90 % of the backbone resonances of the perdeuterated primase-polymerase ORF904, which contains 331 amino acid residues and has a molecular weight of 38.4 kDa.

Transforming plastic surfaces with electrophilic backbones from hydrophobic to hydrophilic.

Science.gov (United States)

Kim, Samuel; Bowen, Raffick A R; Zare, Richard N

2015-01-28

We demonstrate a simple nonaqueous reaction scheme for transforming the surface of plastics from hydrophobic to hydrophilic. The chemical modification is achieved by base-catalyzed trans-esterification with polyols. It is permanent, does not release contaminants, and causes no optical or mechanical distortion of the plastic. We present contact angle measurements to show successful modification of several types of plastics including poly(ethylene terephthalate) (PET) and polycarbonate (PC). Its applicability to blood analysis is explored using chemically modified PET blood collection tubes and found to be quite satisfactory. We expect this approach will reduce the cost of manufacturing plastic devices with optimized wettability and can be generalized to other types of plastic materials having an electrophilic linkage as its backbone.

Mechanism of interaction of the antileukemic drug cytosine arabinoside with aromatic peptides: role of sugar conformation and peptide backbone.

Science.gov (United States)

Datta, G; Hosur, R V; Verma, N C; Khetrapal, C L; Gurnani, S

1989-01-01

Interaction of the antileukemic drugs, cytosine-arabinoside (Ara-C) and adenosine-arabinoside (Ara-A) and a structural analogue, cytidine, with aromatic dipeptides has been studied by fluorescence and NMR spectroscopy. Ara-C and cytidine bind tryptophanyl and histidyl dipeptides but not tyrosyl dipeptides, while Ara-A does not bind to any of them. Both studies indicate association involving stacking of aromatic moieties. NMR spectra also indicate a protonation of the histidine moiety by Ara-C. In case of cytidine, the chemical shifts observed on binding to His-Phe imply that the backbone protons of the dipeptide participate in the binding. The conformation of the sugar and the base seem to play a very important role in the binding phenomenon as three similar molecules, Ara-C, Ara-A and cytidine bind in totally different ways.

Future High Capacity Backbone Networks

DEFF Research Database (Denmark)

Wang, Jiayuan

are proposed. The work focuses on energy efficient routing algorithms in a dynamic optical core network environment, with Generalized MultiProtocol Label Switching (GMPLS) as the control plane. Energy ef- ficient routing algorithms for energy savings and CO2 savings are proposed, and their performance...... aiming for reducing the dynamic part of the energy consumption of the network may increase the fixed part of the energy consumption meanwhile. In the second half of the thesis, the conflict between energy efficiency and Quality of Service (QoS) is addressed by introducing a novel software defined......This thesis - Future High Capacity Backbone Networks - deals with the energy efficiency problems associated with the development of future optical networks. In the first half of the thesis, novel approaches for using multiple/single alternative energy sources for improving energy efficiency...

Smectic order and backbone anisotropy of a side-chain liquid crystalline polymer by Small-Angle Neutron Scattering

Science.gov (United States)

Noirez, L.; Pépy, G.; Keller, P.; Benguigui, L.

1991-07-01

We have simultaneously measured, for the first time, the extension of the polymer backbone of a side-chain liquid crystalline polymer and the intensity of the 001 Bragg reflection, which gives the smectic order parameter Psi as a function of temperature in the smectic phase. We have qualitatively demonstrated that the more the smectic phase is ordered, the more the polymer backbone is localized between the mesogenic layers. It is shown that the Landau theory allows us to relate the radius of gyration parallel to the magnetic field of the polymer backbone to the smectic order parameter. We also show that the Renz-Warner theory is suitable at low temperatures.

NMR backbone resonance assignments of the prodomain variants of BDNF in the urea denatured state.

Science.gov (United States)

Wang, Jing; Bains, Henrietta; Anastasia, Agustin; Bracken, Clay

2018-04-01

Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family of proteins which plays a central role in neuronal survival, growth, plasticity and memory. A single Val66Met variant has been identified in the prodomain of human BDNF that is associated with anxiety, depression and memory disorders. The structural differences within the full-length prodomain Val66 and Met66 isoforms could shed light on the mechanism of action of the Met66 and its impact on the development of neuropsychiatric-associated disorders. In the present study, we report the backbone 1 H, 13 C, and 15 N NMR assignments of both full-length Val66 and Met66 prodomains in the presence of 2 M urea. These conditions were utilized to suppress residual structure and aid subsequent native state structural investigations aimed at mapping and identifying variant-dependent conformational differences under native-state conditions.

Empirical correlation between protein backbone {sup 15}N and {sup 13}C secondary chemical shifts and its application to nitrogen chemical shift re-referencing

Energy Technology Data Exchange (ETDEWEB)

Wang Liya [Cold Spring Harbor Laboratory (United States); Markley, John L. [University of Wisconsin, Biochemistry Department (United States)], E-mail: markley@nmrfam.wisc.edu

2009-06-15

The linear analysis of chemical shifts (LACS) has provided a robust method for identifying and correcting {sup 13}C chemical shift referencing problems in data from protein NMR spectroscopy. Unlike other approaches, LACS does not require prior knowledge of the three-dimensional structure or inference of the secondary structure of the protein. It also does not require extensive assignment of the NMR data. We report here a way of extending the LACS approach to {sup 15}N NMR data from proteins, so as to enable the detection and correction of inconsistencies in chemical shift referencing for this nucleus. The approach is based on our finding that the secondary {sup 15}N chemical shift of the backbone nitrogen atom of residue i is strongly correlated with the secondary chemical shift difference (experimental minus random coil) between the alpha and beta carbons of residue i - 1. Thus once alpha and beta {sup 13}C chemical shifts are available (their difference is referencing error-free), the {sup 15}N referencing can be validated, and an appropriate offset correction can be derived. This approach can be implemented prior to a structure determination and can be used to analyze potential referencing problems in database data not associated with three-dimensional structure. Application of the LACS algorithm to the current BMRB protein chemical shift database, revealed that nearly 35% of the BMRB entries have {delta}{sup 15}N values mis-referenced by over 0.7 ppm and over 25% of them have {delta}{sup 1}H{sup N} values mis-referenced by over 0.12 ppm. One implication of the findings reported here is that a backbone {sup 15}N chemical shift provides a better indicator of the conformation of the preceding residue than of the residue itself.

Fabrication and structural analysis of polyrotaxane fibers and films

Energy Technology Data Exchange (ETDEWEB)

Sakai, Yasuhiro; Ueda, Kentaro; Yokoyama, Hideaki; Ito, Kohzo [Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwano-ha, Kashiwa, Chiba 277-8561 (Japan); Katsuyama, Naoya; Shimizu, Koji; Sato, Shunya; Kuroiwa, Jun; Teramoto, Akira; Abe, Koji [Faculty of Textile Science and Technology, Shinshu University, Tokida 3-15-1, Ueda, Nagano 386-8567 (Japan); Araki, Jun, E-mail: sakai@molle.k.u-tokyo.ac.jp, E-mail: kohzo@k.u-tokyo.ac.jp [International Young Researchers Empowerment Center, Shinshu University, Tokida 3-15-1, Ueda, Nagano 386-8567 (Japan)

2011-07-20

Polyrotaxane (PR), a typical example of topological supramolecular architecture, consists of multiple cyclic molecules threaded onto a linear polymer backbone and capped with bulky end-groups. The PR system of polyethylene glycol and {alpha}-cyclodextrin ({alpha}-CD) has been extensively studied for its facile synthesis, unique molecular structure, and possible applications for various smart materials. We have previously demonstrated the fabrication of PR-based fibers without chemical cross-links by wet spinning of PR solution. In this paper, we investigate the crystal structure of {alpha}-CDs in PR fibers and the effect of drawing on it. The {alpha}-CDs in PR fiber are found to form hexagonal channel-type structure. The drawing process promotes formation of the packing arrangement of {alpha}-CDs in the c-axis because of the sliding of {alpha}-CD molecules along the polymer backbone. In addition, we demonstrate the preparation of an elastomeric PR film having similar network structure to the fibers and ethylene glycol oligomer as plasticizer.

Fabrication and structural analysis of polyrotaxane fibers and films

International Nuclear Information System (INIS)

Sakai, Yasuhiro; Ueda, Kentaro; Yokoyama, Hideaki; Ito, Kohzo; Katsuyama, Naoya; Shimizu, Koji; Sato, Shunya; Kuroiwa, Jun; Teramoto, Akira; Abe, Koji; Araki, Jun

2011-01-01

Polyrotaxane (PR), a typical example of topological supramolecular architecture, consists of multiple cyclic molecules threaded onto a linear polymer backbone and capped with bulky end-groups. The PR system of polyethylene glycol and α-cyclodextrin (α-CD) has been extensively studied for its facile synthesis, unique molecular structure, and possible applications for various smart materials. We have previously demonstrated the fabrication of PR-based fibers without chemical cross-links by wet spinning of PR solution. In this paper, we investigate the crystal structure of α-CDs in PR fibers and the effect of drawing on it. The α-CDs in PR fiber are found to form hexagonal channel-type structure. The drawing process promotes formation of the packing arrangement of α-CDs in the c-axis because of the sliding of α-CD molecules along the polymer backbone. In addition, we demonstrate the preparation of an elastomeric PR film having similar network structure to the fibers and ethylene glycol oligomer as plasticizer.

Building alternate protein structures using the elastic network model.

Science.gov (United States)

Yang, Qingyi; Sharp, Kim A

2009-02-15

We describe a method for efficiently generating ensembles of alternate, all-atom protein structures that (a) differ significantly from the starting structure, (b) have good stereochemistry (bonded geometry), and (c) have good steric properties (absence of atomic overlap). The method uses reconstruction from a series of backbone framework structures that are obtained from a modified elastic network model (ENM) by perturbation along low-frequency normal modes. To ensure good quality backbone frameworks, the single force parameter ENM is modified by introducing two more force parameters to characterize the interaction between the consecutive carbon alphas and those within the same secondary structure domain. The relative stiffness of the three parameters is parameterized to reproduce B-factors, while maintaining good bonded geometry. After parameterization, violations of experimental Calpha-Calpha distances and Calpha-Calpha-Calpha pseudo angles along the backbone are reduced to less than 1%. Simultaneously, the average B-factor correlation coefficient improves to R = 0.77. Two applications illustrate the potential of the approach. (1) 102,051 protein backbones spanning a conformational space of 15 A root mean square deviation were generated from 148 nonredundant proteins in the PDB database, and all-atom models with minimal bonded and nonbonded violations were produced from this ensemble of backbone structures using the SCWRL side chain building program. (2) Improved backbone templates for homology modeling. Fifteen query sequences were each modeled on two targets. For each of the 30 target frameworks, dozens of improved templates could be produced In all cases, improved full atom homology models resulted, of which 50% could be identified blind using the D-Fire statistical potential. (c) 2008 Wiley-Liss, Inc.

Performance Analysis of Space Information Networks with Backbone Satellite Relaying for Vehicular Networks

Directory of Open Access Journals (Sweden)

Jian Jiao

2017-01-01

Full Text Available Space Information Network (SIN with backbone satellites relaying for vehicular network (VN communications is regarded as an effective strategy to provide diverse vehicular services in a seamless, efficient, and cost-effective manner in rural areas and highways. In this paper, we investigate the performance of SIN return channel cooperative communications via an amplify-and-forward (AF backbone satellite relaying for VN communications, where we assume that both of the source-destination and relay-destination links undergo Shadowed-Rician fading and the source-relay link follows Rician fading, respectively. In this SIN-assisted VN communication scenario, we first obtain the approximate statistical distributions of the equivalent end-to-end signal-to-noise ratio (SNR of the system. Then, we derive the closed-form expressions to efficiently evaluate the average symbol error rate (ASER of the system. Furthermore, the ASER expressions are taking into account the effect of satellite perturbation of the backbone relaying satellite, which reveal the accumulated error of the antenna pointing error. Finally, simulation results are provided to verify the accuracy of our theoretical analysis and show the impact of various parameters on the system performance.

Sub-nanoscale surface ruggedness provides a water-tight seal for exposed regions in soluble protein structure.

Directory of Open Access Journals (Sweden)

Erica Schulz

2010-09-01

Full Text Available Soluble proteins must maintain backbone hydrogen bonds (BHBs water-tight to ensure structural integrity. This protection is often achieved by burying the BHBs or wrapping them through intermolecular associations. On the other hand, water has low coordination resilience, with loss of hydrogen-bonding partnerships carrying significant thermodynamic cost. Thus, a core problem in structural biology is whether natural design actually exploits the water coordination stiffness to seal the backbone in regions that are exposed to the solvent. This work explores the molecular design features that make this type of seal operative, focusing on the side-chain arrangements that shield the protein backbone. We show that an efficient sealing is achieved by adapting the sub-nanoscale surface topography to the stringency of water coordination: an exposed BHB may be kept dry if the local concave curvature is small enough to impede formation of the coordination shell of a penetrating water molecule. Examination of an exhaustive database of uncomplexed proteins reveals that exposed BHBs invariably occur within such sub-nanoscale cavities in native folds, while this level of local ruggedness is absent in other regions. By contrast, BHB exposure in misfolded proteins occurs with larger local curvature promoting backbone hydration and consequently, structure disruption. These findings unravel physical constraints fitting a spatially dependent least-action for water coordination, introduce a molecular design concept, and herald the advent of water-tight peptide-based materials with sufficient backbone exposure to remain flexible.

Hidden Markov model approach for identifying the modular framework of the protein backbone.

Science.gov (United States)

Camproux, A C; Tuffery, P; Chevrolat, J P; Boisvieux, J F; Hazout, S

1999-12-01

The hidden Markov model (HMM) was used to identify recurrent short 3D structural building blocks (SBBs) describing protein backbones, independently of any a priori knowledge. Polypeptide chains are decomposed into a series of short segments defined by their inter-alpha-carbon distances. Basically, the model takes into account the sequentiality of the observed segments and assumes that each one corresponds to one of several possible SBBs. Fitting the model to a database of non-redundant proteins allowed us to decode proteins in terms of 12 distinct SBBs with different roles in protein structure. Some SBBs correspond to classical regular secondary structures. Others correspond to a significant subdivision of their bounding regions previously considered to be a single pattern. The major contribution of the HMM is that this model implicitly takes into account the sequential connections between SBBs and thus describes the most probable pathways by which the blocks are connected to form the framework of the protein structures. Validation of the SBBs code was performed by extracting SBB series repeated in recoding proteins and examining their structural similarities. Preliminary results on the sequence specificity of SBBs suggest promising perspectives for the prediction of SBBs or series of SBBs from the protein sequences.

Side chain and backbone contributions of Phe508 to CFTR folding

Energy Technology Data Exchange (ETDEWEB)

Thibodeau, Patrick H.; Brautigam, Chad A.; Machius, Mischa; Thomas, Philip J. (U. of Texas-SMED)

2010-12-07

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an integral membrane protein, cause cystic fibrosis (CF). The most common CF-causing mutant, deletion of Phe508, fails to properly fold. To elucidate the role Phe508 plays in the folding of CFTR, missense mutations at this position were generated. Only one missense mutation had a pronounced effect on the stability and folding of the isolated domain in vitro. In contrast, many substitutions, including those of charged and bulky residues, disrupted folding of full-length CFTR in cells. Structures of two mutant nucleotide-binding domains (NBDs) reveal only local alterations of the surface near position 508. These results suggest that the peptide backbone plays a role in the proper folding of the domain, whereas the side chain plays a role in defining a surface of NBD1 that potentially interacts with other domains during the maturation of intact CFTR.

Cross-correlated relaxation rates between protein backbone H–X dipolar interactions

International Nuclear Information System (INIS)

Vögeli, Beat

2017-01-01

The relaxation interference between dipole–dipole interactions of two separate spin pairs carries structural and dynamics information. In particular, when compared to individual dynamic behavior of those spin pairs, such cross-correlated relaxation (CCR) rates report on the correlation between the spin pairs. We have recently mapped out correlated motion along the backbone of the protein GB3, using CCR rates among and between consecutive H N –N and H α –C α dipole–dipole interactions. Here, we provide a detailed account of the measurement of the four types of CCR rates. All rates were obtained from at least two different pulse sequences, of which the yet unpublished ones are presented. Detailed comparisons between the different methods and corrections for unwanted pathways demonstrate that the averaged CCR rates are highly accurate and precise with errors of 1.5–3% of the entire value ranges.

Cross-correlated relaxation rates between protein backbone H–X dipolar interactions

Energy Technology Data Exchange (ETDEWEB)

Vögeli, Beat, E-mail: beat.vogeli@ucdenver.edu [University of Colorado Denver, Department of Biochemistry and Molecular Genetics (United States)

2017-03-15

The relaxation interference between dipole–dipole interactions of two separate spin pairs carries structural and dynamics information. In particular, when compared to individual dynamic behavior of those spin pairs, such cross-correlated relaxation (CCR) rates report on the correlation between the spin pairs. We have recently mapped out correlated motion along the backbone of the protein GB3, using CCR rates among and between consecutive H{sup N}–N and H{sup α}–C{sup α} dipole–dipole interactions. Here, we provide a detailed account of the measurement of the four types of CCR rates. All rates were obtained from at least two different pulse sequences, of which the yet unpublished ones are presented. Detailed comparisons between the different methods and corrections for unwanted pathways demonstrate that the averaged CCR rates are highly accurate and precise with errors of 1.5–3% of the entire value ranges.

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A-T phosphoramidite building blocks.

Science.gov (United States)

Schmidtgall, Boris; Höbartner, Claudia; Ducho, Christian

2015-01-01

Modifications of the nucleic acid backbone are essential for the development of oligonucleotide-derived bioactive agents. The NAA-modification represents a novel artificial internucleotide linkage which enables the site-specific introduction of positive charges into the otherwise polyanionic backbone of DNA oligonucleotides. Following initial studies with the introduction of the NAA-linkage at T-T sites, it is now envisioned to prepare NAA-modified oligonucleotides bearing the modification at X-T motifs (X = A, C, G). We have therefore developed the efficient and stereoselective synthesis of NAA-linked 'dimeric' A-T phosphoramidite building blocks for automated DNA synthesis. Both the (S)- and the (R)-configured NAA-motifs were constructed with high diastereoselectivities to furnish two different phosphoramidite reagents, which were employed for the solid phase-supported automated synthesis of two NAA-modified DNA oligonucleotides. This represents a significant step to further establish the NAA-linkage as a useful addition to the existing 'toolbox' of backbone modifications for the design of bioactive oligonucleotide analogues.

Three-Dimensional Protein Fold Determination from Backbone Amide Pseudocontact Shifts Generated by Lanthanide Tags at Multiple Sites

KAUST Repository

Yagi, Hiromasa

2013-06-01

Site-specific attachment of paramagnetic lanthanide ions to a protein generates pseudocontact shifts (PCS) in the nuclear magnetic resonance (NMR) spectra of the protein that are easily measured as changes in chemical shifts. By labeling the protein with lanthanide tags at four different sites, PCSs are observed for most amide protons and accurate information is obtained about their coordinates in three-dimensional space. The approach is demonstrated with the chaperone ERp29, for which large differences have been reported between X-ray and NMR structures of the C-terminal domain, ERp29-C. The results unambiguously show that the structure of rat ERp29-C in solution is similar to the crystal structure of human ERp29-C. PCSs of backbone amides were the only structural restraints required. Because these can be measured for more dilute protein solutions than other NMR restraints, the approach greatly widens the range of proteins amenable to structural studies in solution. © 2013 Elsevier Ltd. All rights reserved.

Structural constraints-based evaluation of immunogenic avirulent toxins from Clostridium botulinum C2 and C3 toxins as subunit vaccines.

Science.gov (United States)

Prisilla, A; Prathiviraj, R; Sasikala, R; Chellapandi, P

2016-10-01

Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 and C3 toxins in addition to botulinum neurotoxins in avian and mammalian cells. C2 and C3 toxins are members of bacterial ADP-ribosyltransferase superfamily, which modify the eukaryotic cell surface proteins by ADP-ribosylation reaction. Herein, the mutant proteins with lack of catalytic and pore forming function derived from C2 (C2I and C2II) and C3 toxins were computationally evaluated to understand their structure-function integrity. We have chosen many structural constraints including local structural environment, folding process, backbone conformation, conformational dynamic sub-space, NAD-binding specificity and antigenic determinants for screening of suitable avirulent toxins. A total of 20 avirulent mutants were identified out of 23 mutants, which were experimentally produced by site-directed mutagenesis. No changes in secondary structural elements in particular to α-helices and β-sheets and also in fold rate of all-β classes. Structural stability was maintained by reordered hydrophobic and hydrogen bonding patterns. Molecular dynamic studies suggested that coupled mutations may restrain the binding affinity to NAD(+) or protein substrate upon structural destabilization. Avirulent toxins of this study have stable energetic backbone conformation with a common blue print of folding process. Molecular docking studies revealed that avirulent mutants formed more favorable hydrogen bonding with the side-chain of amino acids near to conserved NAD-binding core, despite of restraining NAD-binding specificity. Thus, structural constraints in the avirulent toxins would determine their immunogenic nature for the prioritization of protein-based subunit vaccine/immunogens to avian and veterinary animals infected with C. botulinum. Copyright © 2016 Elsevier B.V. All rights reserved.

Oligomerized backbone pilin helps piliated Lactococcus lactis to withstand shear flow.

Science.gov (United States)

Castelain, Mickaël; Duviau, Marie-Pierre; Oxaran, Virginie; Schmitz, Philippe; Cocaign-Bousquet, Muriel; Loubière, Pascal; Piard, Jean-Christophe; Mercier-Bonin, Muriel

2016-09-01

The present work focuses on the role of pili present at the cell surface of Lactococcus lactis in bacterial adhesion to abiotic (hydrophobic polystyrene) and biotic (mucin-coated polystyrene) surfaces. Native pili-displaying strains and isogenic derivatives in which pilins or sortase C structural genes had been modified were used. Surface physico-chemistry, morphology and shear-flow-induced detachment of lactococcal cells were evaluated. The involvement of pili in L. lactis adhesion was clearly demonstrated, irrespective of the surface characteristics (hydrophobic/hydrophilic, presence or not of specific binding sites). The accessory pilin, PilC, and the backbone pilin, PilB, were revealed to play a major role in adhesion, provided that the PilB was present in its polymerized form. Within the population fraction that remained attached to the surface under increasing shear flow, different association behaviors were observed, showing that pili could serve as anchoring sites thus hampering the effect of shear flow on cell orientation and detachment.

Probing the role of backbone hydrogen bonds in protein-peptide interactions by amide-to-ester mutations

DEFF Research Database (Denmark)

Eildal, Jonas N N; Hultqvist, Greta; Balle, Thomas

2013-01-01

-protein interactions, those of the PDZ domain family involve formation of intermolecular hydrogen bonds: C-termini or internal linear motifs of proteins bind as β-strands to form an extended antiparallel β-sheet with the PDZ domain. Whereas extensive work has focused on the importance of the amino acid side chains...... of the protein ligand, the role of the backbone hydrogen bonds in the binding reaction is not known. Using amide-to-ester substitutions to perturb the backbone hydrogen-bonding pattern, we have systematically probed putative backbone hydrogen bonds between four different PDZ domains and peptides corresponding...... to natural protein ligands. Amide-to-ester mutations of the three C-terminal amides of the peptide ligand severely affected the affinity with the PDZ domain, demonstrating that hydrogen bonds contribute significantly to ligand binding (apparent changes in binding energy, ΔΔG = 1.3 to >3.8 kcal mol(-1...

Easy and unambiguous sequential assignments of intrinsically disordered proteins by correlating the backbone 15N or 13C′ chemical shifts of multiple contiguous residues in highly resolved 3D spectra

International Nuclear Information System (INIS)

Yoshimura, Yuichi; Kulminskaya, Natalia V.; Mulder, Frans A. A.

2015-01-01

Sequential resonance assignment strategies are typically based on matching one or two chemical shifts of adjacent residues. However, resonance overlap often leads to ambiguity in resonance assignments in particular for intrinsically disordered proteins. We investigated the potential of establishing connectivity through the three-bond couplings between sequentially adjoining backbone carbonyl carbon nuclei, combined with semi-constant time chemical shift evolution, for resonance assignments of small folded and larger unfolded proteins. Extended sequential connectivity strongly lifts chemical shift degeneracy of the backbone nuclei in disordered proteins. We show here that 3D (H)N(COCO)NH and (HN)CO(CO)NH experiments with relaxation-optimized multiple pulse mixing correlate up to seven adjacent backbone amide nitrogen or carbonyl carbon nuclei, respectively, and connections across proline residues are also obtained straightforwardly. Multiple, recurrent long-range correlations with ultra-high resolution allow backbone 1 H N , 15 N H , and 13 C′ resonance assignments to be completed from a single pair of 3D experiments

The Prediction of Botulinum Toxin Structure Based on in Silico and in Vitro Analysis

Science.gov (United States)

Suzuki, Tomonori; Miyazaki, Satoru

2011-01-01

Many of biological system mediated through protein-protein interactions. Knowledge of protein-protein complex structure is required for understanding the function. The determination of huge size and flexible protein-protein complex structure by experimental studies remains difficult, costly and five-consuming, therefore computational prediction of protein structures by homolog modeling and docking studies is valuable method. In addition, MD simulation is also one of the most powerful methods allowing to see the real dynamics of proteins. Here, we predict protein-protein complex structure of botulinum toxin to analyze its property. These bioinformatics methods are useful to report the relation between the flexibility of backbone structure and the activity.

An Unusual Conformational Isomer of Verrucosidin Backbone from a Hydrothermal Vent Fungus, Penicillium sp. Y-50-10.

Science.gov (United States)

Pan, Chengqian; Shi, Yutong; Auckloo, Bibi Nazia; Chen, Xuegang; Chen, Chen-Tung Arthur; Tao, Xinyi; Wu, Bin

2016-08-18

A new verrucosidin derivative, methyl isoverrucosidinol (1), was isolated from the marine fungus Penicillium sp. Y-50-10, dwelling in sulfur rich sediment in the Kueishantao hydrothermal vents off Taiwan. The structure was established by spectroscopic means including HRMS and 2D-NMR spectroscopic analysis. The absolute configuration was defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Among hitherto known compounds with a verrucosidine backbone isolated from natural resource, compound 1 represents the first example of a new conformational isomer of its skeleton, exhibiting antibiotic activity against Bacillus subtilis with MIC value 32 μg/mL.

Aromatic Copolyamides with Anthrazoline Units in the Backbone: Synthesis, Characterization, Pervaporation Application

Directory of Open Access Journals (Sweden)

Galina A. Polotskaya

2016-10-01

Full Text Available Copolyamides with anthrazoline units in the backbone (coPA were synthesized and dense nonporous films were prepared by solvent evaporation. Glass transition temperature, density, and fractional free volume were determined for the dense nonporous films composed of polyamide and two of its copolymers containing 20 and 30 mol % anthrazoline units in the backbone. Transport properties of the polymer films were estimated by sorption and pervaporation tests toward methanol, toluene, and their mixtures. An increase in anthrazoline fragments content leads to an increasing degree of methanol sorption but to a decreasing degree of toluene sorption. Pervaporation of a methanol–toluene mixture was studied over a wide range of feed concentration (10–90 wt % methanol. Maximal separation factor was observed for coPA-20 containing 20 mol % fragments with anthrazoline units; maximal total flux was observed for coPA-30 with the highest fractional free volume.

Ca-C backbone fragmentation dominates in electron detachment dissociation of gas-phase polypeptide polyanions

DEFF Research Database (Denmark)

Kjeldsen, Frank; Silivra, Oleg A; Ivonin, Igor A

2005-01-01

the dissociation of oxidized radical anions [M-nH]((n-1)-*. We demonstrate that C(alpha)-C cleavages, which are otherwise rarely observed in tandem mass spectrometry, can account for most of the backbone fragmentation, with even-electron x fragments dominating over radical a* ions. Ab initio calculations at the B3...... LYP level of theory with the 6-311+G(2 p,2 d)//6-31+G(d,p) basis set suggested a unidirectional mechanism for EDD (cleavage always N-terminal to the radical site), with a*, x formation being favored over a, x* fragmentation by 74.2 kJ mol(-1). Thus, backbone C(alpha)-C bonds N-terminal to proline...

de Vries liquid crystals based on a chiral 5-phenylpyrimidine benzoate core with a tri- and tetra-carbosilane backbone

Science.gov (United States)

Sreenilayam, S. P.; Rodriguez-Lojo, D.; Agra-Kooijman, D. M.; Vij, J. K.; Panov, V. P.; Panov, A.; Fisch, M. R.; Kumar, Satyendra; Stevenson, P. J.

2018-02-01

New chiral de Vries smectic liquid-crystalline compounds are designed, synthesized, and investigated for perspective applications in defect-free bistable surface-stabilized ferroelectric liquid-crystal displays. In these compounds, a 5-phenyl-pyrimidine benzoate core is terminated on one side by a tri- or tetra-carbosilane group linked through an alkoxy group and an alkyl spacer and on the opposite side terminated by a chiral 2-octanol group. The stereogenic center contains either a methyl or perfluoromethyl functional group. These compounds exhibit Iso-Sm A*-Sm C*-Sm X -Cr phases under cooling from the isotropic state. Measurements of the temperature-dependent smectic layer spacing by x-ray diffraction experiments combined with the measured apparent optical tilt angle and the birefringence reveal that Sm A* phase in these compounds is of the de Vries type. In addition, the chiral compound with a tetra-carbosilane backbone, DR277, exhibits good de Vries properties with the Sm C* phase exhibited over a wide temperature range. By varying the carbosilane end group, the de Vries properties are enhanced, that is, the layer shrinkage of ˜1.9 % for the tri-carbosilane DR276 is reduced to ˜0.9 % for tetra-carbosilane DR277 at 10°C below Sm A* to Sm C* transition temperature, TAC. For DR277, the reduction factor R ≈0.22 for T =(TAC-10 )°C is reasonably low and the apparent optical tilt angle θapp=35.1°, hence this compound is a "good de Vries smectic" LC. Therefore, synthesis of the chiral mesogen with an even higher number of carbosilane groups may lead to a further reduction or even zero-layer shrinkage exhibited at TAC with Sm C* phase extending over a wide temperature range close to the room temperature for perspective suitability in device applications. Our results for 5-phenyl-pyrimidine benzoate core-based compounds support a recently drawn conclusion by Schubert et al. [J. Mater. Chem. C 4, 8483 (2016), 10.1039/C6TC03120J] from a different compound, namely

Tertiary alphabet for the observable protein structural universe.

Science.gov (United States)

Mackenzie, Craig O; Zhou, Jianfu; Grigoryan, Gevorg

2016-11-22

Here, we systematically decompose the known protein structural universe into its basic elements, which we dub tertiary structural motifs (TERMs). A TERM is a compact backbone fragment that captures the secondary, tertiary, and quaternary environments around a given residue, comprising one or more disjoint segments (three on average). We seek the set of universal TERMs that capture all structure in the Protein Data Bank (PDB), finding remarkable degeneracy. Only ∼600 TERMs are sufficient to describe 50% of the PDB at sub-Angstrom resolution. However, more rare geometries also exist, and the overall structural coverage grows logarithmically with the number of TERMs. We go on to show that universal TERMs provide an effective mapping between sequence and structure. We demonstrate that TERM-based statistics alone are sufficient to recapitulate close-to-native sequences given either NMR or X-ray backbones. Furthermore, sequence variability predicted from TERM data agrees closely with evolutionary variation. Finally, locations of TERMs in protein chains can be predicted from sequence alone based on sequence signatures emergent from TERM instances in the PDB. For multisegment motifs, this method identifies spatially adjacent fragments that are not contiguous in sequence-a major bottleneck in structure prediction. Although all TERMs recur in diverse proteins, some appear specialized for certain functions, such as interface formation, metal coordination, or even water binding. Structural biology has benefited greatly from previously observed degeneracies in structure. The decomposition of the known structural universe into a finite set of compact TERMs offers exciting opportunities toward better understanding, design, and prediction of protein structure.

Structural insights into the evolution of a sexy protein: novel topology and restricted backbone flexibility in a hypervariable pheromone from the red-legged salamander, Plethodon shermani.

Science.gov (United States)

Wilburn, Damien B; Bowen, Kathleen E; Doty, Kari A; Arumugam, Sengodagounder; Lane, Andrew N; Feldhoff, Pamela W; Feldhoff, Richard C

2014-01-01

In response to pervasive sexual selection, protein sex pheromones often display rapid mutation and accelerated evolution of corresponding gene sequences. For proteins, the general dogma is that structure is maintained even as sequence or function may rapidly change. This phenomenon is well exemplified by the three-finger protein (TFP) superfamily: a diverse class of vertebrate proteins co-opted for many biological functions - such as components of snake venoms, regulators of the complement system, and coordinators of amphibian limb regeneration. All of the >200 structurally characterized TFPs adopt the namesake "three-finger" topology. In male red-legged salamanders, the TFP pheromone Plethodontid Modulating Factor (PMF) is a hypervariable protein such that, through extensive gene duplication and pervasive sexual selection, individual male salamanders express more than 30 unique isoforms. However, it remained unclear how this accelerated evolution affected the protein structure of PMF. Using LC/MS-MS and multidimensional NMR, we report the 3D structure of the most abundant PMF isoform, PMF-G. The high resolution structural ensemble revealed a highly modified TFP structure, including a unique disulfide bonding pattern and loss of secondary structure, that define a novel protein topology with greater backbone flexibility in the third peptide finger. Sequence comparison, models of molecular evolution, and homology modeling together support that this flexible third finger is the most rapidly evolving segment of PMF. Combined with PMF sequence hypervariability, this structural flexibility may enhance the plasticity of PMF as a chemical signal by permitting potentially thousands of structural conformers. We propose that the flexible third finger plays a critical role in PMF:receptor interactions. As female receptors co-evolve, this flexibility may allow PMF to still bind its receptor(s) without the immediate need for complementary mutations. Consequently, this unique

Structural insights into the evolution of a sexy protein: novel topology and restricted backbone flexibility in a hypervariable pheromone from the red-legged salamander, Plethodon shermani.

Directory of Open Access Journals (Sweden)

Damien B Wilburn

Full Text Available In response to pervasive sexual selection, protein sex pheromones often display rapid mutation and accelerated evolution of corresponding gene sequences. For proteins, the general dogma is that structure is maintained even as sequence or function may rapidly change. This phenomenon is well exemplified by the three-finger protein (TFP superfamily: a diverse class of vertebrate proteins co-opted for many biological functions - such as components of snake venoms, regulators of the complement system, and coordinators of amphibian limb regeneration. All of the >200 structurally characterized TFPs adopt the namesake "three-finger" topology. In male red-legged salamanders, the TFP pheromone Plethodontid Modulating Factor (PMF is a hypervariable protein such that, through extensive gene duplication and pervasive sexual selection, individual male salamanders express more than 30 unique isoforms. However, it remained unclear how this accelerated evolution affected the protein structure of PMF. Using LC/MS-MS and multidimensional NMR, we report the 3D structure of the most abundant PMF isoform, PMF-G. The high resolution structural ensemble revealed a highly modified TFP structure, including a unique disulfide bonding pattern and loss of secondary structure, that define a novel protein topology with greater backbone flexibility in the third peptide finger. Sequence comparison, models of molecular evolution, and homology modeling together support that this flexible third finger is the most rapidly evolving segment of PMF. Combined with PMF sequence hypervariability, this structural flexibility may enhance the plasticity of PMF as a chemical signal by permitting potentially thousands of structural conformers. We propose that the flexible third finger plays a critical role in PMF:receptor interactions. As female receptors co-evolve, this flexibility may allow PMF to still bind its receptor(s without the immediate need for complementary mutations. Consequently

Protein structure refinement using a quantum mechanics-based chemical shielding predictor.

Science.gov (United States)

Bratholm, Lars A; Jensen, Jan H

2017-03-01

The accurate prediction of protein chemical shifts using a quantum mechanics (QM)-based method has been the subject of intense research for more than 20 years but so far empirical methods for chemical shift prediction have proven more accurate. In this paper we show that a QM-based predictor of a protein backbone and CB chemical shifts (ProCS15, PeerJ , 2016, 3, e1344) is of comparable accuracy to empirical chemical shift predictors after chemical shift-based structural refinement that removes small structural errors. We present a method by which quantum chemistry based predictions of isotropic chemical shielding values (ProCS15) can be used to refine protein structures using Markov Chain Monte Carlo (MCMC) simulations, relating the chemical shielding values to the experimental chemical shifts probabilistically. Two kinds of MCMC structural refinement simulations were performed using force field geometry optimized X-ray structures as starting points: simulated annealing of the starting structure and constant temperature MCMC simulation followed by simulated annealing of a representative ensemble structure. Annealing of the CHARMM structure changes the CA-RMSD by an average of 0.4 Å but lowers the chemical shift RMSD by 1.0 and 0.7 ppm for CA and N. Conformational averaging has a relatively small effect (0.1-0.2 ppm) on the overall agreement with carbon chemical shifts but lowers the error for nitrogen chemical shifts by 0.4 ppm. If an amino acid specific offset is included the ProCS15 predicted chemical shifts have RMSD values relative to experiments that are comparable to popular empirical chemical shift predictors. The annealed representative ensemble structures differ in CA-RMSD relative to the initial structures by an average of 2.0 Å, with >2.0 Å difference for six proteins. In four of the cases, the largest structural differences arise in structurally flexible regions of the protein as determined by NMR, and in the remaining two cases, the large structural

Effects of backbone conformation and surface texture of polyimide alignment film on the pretilt angle of liquid crystals

International Nuclear Information System (INIS)

Chang, Chi-Jung; Chou, Ray-Lin; Lin, Yu-Chi; Liang, Bau-Jy; Chen, Jyun-Ji

2011-01-01

Polyimides (PIs) with different inclination angle of polymer backbones, together with polar hydroxyl group and/or nonpolar trifluoromethyl group at various sites of the backbone were synthesized and used as liquid crystal alignment layers. The molecular conformation, surface chemistry, surface energy, surface morphology, and pretilt angle of the PI film were investigated. The distributions of fluorinated group and hydroxyl group at different depths of the PI surfaces were analyzed by X-ray photoelectron spectroscopy. Effects of the conformation of the PI molecular backbone on the surface morphology of the rubbed PI layer, the pretilt angle and surface energy of the alignment film were studied. The PI which contains both nonpolar fluorinated groups sticking out of the surface and the polar hydroxyl groups on the surface exhibits high pretilt angle.

Combining Rosetta with molecular dynamics (MD): A benchmark of the MD-based ensemble protein design.

Science.gov (United States)

Ludwiczak, Jan; Jarmula, Adam; Dunin-Horkawicz, Stanislaw

2018-07-01

Computational protein design is a set of procedures for computing amino acid sequences that will fold into a specified structure. Rosetta Design, a commonly used software for protein design, allows for the effective identification of sequences compatible with a given backbone structure, while molecular dynamics (MD) simulations can thoroughly sample near-native conformations. We benchmarked a procedure in which Rosetta design is started on MD-derived structural ensembles and showed that such a combined approach generates 20-30% more diverse sequences than currently available methods with only a slight increase in computation time. Importantly, the increase in diversity is achieved without a loss in the quality of the designed sequences assessed by their resemblance to natural sequences. We demonstrate that the MD-based procedure is also applicable to de novo design tasks started from backbone structures without any sequence information. In addition, we implemented a protocol that can be used to assess the stability of designed models and to select the best candidates for experimental validation. In sum our results demonstrate that the MD ensemble-based flexible backbone design can be a viable method for protein design, especially for tasks that require a large pool of diverse sequences. Copyright © 2018 Elsevier Inc. All rights reserved.

Neural Networks for protein Structure Prediction

DEFF Research Database (Denmark)

Bohr, Henrik

1998-01-01

This is a review about neural network applications in bioinformatics. Especially the applications to protein structure prediction, e.g. prediction of secondary structures, prediction of surface structure, fold class recognition and prediction of the 3-dimensional structure of protein backbones...

Influence of Backbone Fluorination in Regioregular Poly(3-alkyl-4-fluoro)thiophenes

KAUST Repository

Fei, Zhuping

2015-06-03

© 2015 American Chemical Society. We report two strategies toward the synthesis of 3-alkyl-4-fluorothiophenes containing straight (hexyl and octyl) and branched (2-ethylhexyl) alkyl groups. We demonstrate that treatment of the dibrominated monomer with 1 equiv of alkyl Grignard reagent leads to the formation of a single regioisomer as a result of the pronounced directing effect of the fluorine group. Polymerization of the resulting species affords highly regioregular poly(3-alkyl-4-fluoro)thiophenes. Comparison of their properties to those of the analogous non-fluorinated polymers shows that backbone fluorination leads to an increase in the polymer ionization potential without a significant change in optical band gap. Fluorination also results in an enhanced tendency to aggregate in solution, which is ascribed to a more co-planar backbone on the basis of Raman and DFT calculations. Average charge carrier mobilities in field-effect transistors are found to increase by up to a factor of 5 for the fluorinated polymers.

Assignment of protein backbone resonances using connectivity, torsion angles and 13Cα chemical shifts

International Nuclear Information System (INIS)

Morris, Laura C.; Valafar, Homayoun; Prestegard, James H.

2004-01-01

A program is presented which will return the most probable sequence location for a short connected set of residues in a protein given just 13 C α chemical shifts (δ( 13 C α )) and data restricting the φ and ψ backbone angles. Data taken from both the BioMagResBank and the Protein Data Bank were used to create a probability density function (PDF) using a multivariate normal distribution in δ( 13 C α ), φ, and ψ space for each amino acid residue. Extracting and combining probabilities for particular amino acid residues in a short proposed sequence yields a score indicative of the correctness of the proposed assignment. The program is illustrated using several proteins for which structure and 13 C α chemical shift data are available

Data Acquisition Backbone Core DABC

International Nuclear Information System (INIS)

Adamczewski, J; Essel, H G; Kurz, N; Linev, S

2008-01-01

For the new experiments at FAIR new concepts of data acquisition systems have to be developed like the distribution of self-triggered, time stamped data streams over high performance networks for event building. The Data Acquisition Backbone Core (DABC) is a software package currently under development for FAIR detector tests, readout components test, and data flow investigations. All kinds of data channels (front-end systems) are connected by program plug-ins into functional components of DABC like data input, combiner, scheduler, event builder, analysis and storage components. After detailed simulations real tests of event building over a switched network (InfiniBand clusters with up to 110 nodes) have been performed. With the DABC software more than 900 MByte/s input and output per node can be achieved meeting the most demanding requirements. The software is ready for the implementation of various test beds needed for the final design of data acquisition systems at FAIR. The development of key components is supported by the FutureDAQ project of the European Union (FP6 I3HP JRA1)

Tunable smart digital structure (SDS) to modularly assemble soft actuators with layered adhesive bonding

Science.gov (United States)

Jin, Hu; Dong, Erbao; Xu, Min; Xia, Qirong; Liu, Shuai; Li, Weihua; Yang, Jie

2018-01-01

Many shape memory alloy (SMA)-based soft actuators have specific composite structures and manufacture processes, and are therefore unique. However, these exclusive characteristics limit their capabilities and applications, so in this article a soft and smart digital structure (SDS) is proposed that acts like a modular unit to assemble soft actuators by a layered adhesive bonding process. The SDS is a fully soft structure that encapsulates a digital skeleton consisting of four groups of parallel and independently actuated SMA wires capable of outputting a four-channel tunable force. The layered adhesive bonding process modularly bonds several SDSs with an elastic backbone to fabricate a layered soft actuator where the elastic backbone is used to recover the SDSs in a cooling process using the SMA wires. Two kinds of SDS-based soft actuators were modularly assembled, an actuator, SDS-I, with a two-dimensional reciprocal motion, and an actuator, SDS-II, capable of bi-directional reciprocal motion. The thermodynamics and phase transformation modeling of the SDS-based actuator were analyzed. Several extensional soft actuators were also assembled by bonding the SDS with an anomalous elastic backbone or modularly assembling the SDS-Is and SDS-IIs. These modularly assembled soft actuators delivered more output channels and a complicated motion, e.g., an actinomorphic soft actuator with four SDS-Is jumps in a series of hierarchical heights and directional movement by tuning the input channels of the SDSs. This result showed that the SDS can modularly assemble multifarious soft actuators with diverse capabilities, steerability and tunable outputs.

An Unusual Conformational Isomer of Verrucosidin Backbone from a Hydrothermal Vent Fungus, Penicillium sp. Y-50-10

Directory of Open Access Journals (Sweden)

Chengqian Pan

2016-08-01

Full Text Available A new verrucosidin derivative, methyl isoverrucosidinol (1, was isolated from the marine fungus Penicillium sp. Y-50-10, dwelling in sulfur rich sediment in the Kueishantao hydrothermal vents off Taiwan. The structure was established by spectroscopic means including HRMS and 2D-NMR spectroscopic analysis. The absolute configuration was defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Among hitherto known compounds with a verrucosidine backbone isolated from natural resource, compound 1 represents the first example of a new conformational isomer of its skeleton, exhibiting antibiotic activity against Bacillus subtilis with MIC value 32 μg/mL.

SEVA Linkers: A Versatile and Automatable DNA Backbone Exchange Standard for Synthetic Biology

DEFF Research Database (Denmark)

Kim, Se Hyeuk; Cavaleiro, Mafalda; Rennig, Maja

2016-01-01

flexibility, and different researchers prefer and master different molecular technologies. Here, we describe a new, highly versatile and automatable standard “SEVA linkers” for vector exchange. SEVA linkers enable backbone swapping with 20 combinations of classical enzymatic restriction/ligation, Gibson...

Backbone dynamics of the human CC-chemokine eotaxin

Energy Technology Data Exchange (ETDEWEB)

Ye Jiqing; Mayer, Kristen L.; Stone, Martin J. [Indiana University, Department of Chemistry (United States)

1999-10-15

Eotaxin is a CC chemokine with potent chemoattractant activity towards eosinophils. {sup 15}N NMR relaxation data have been used to characterize the backbone dynamics of recombinant human eotaxin. {sup 15}N longitudinal (R{sub 1}) and transverse (R{sub 2}) auto relaxation rates, heteronuclear {sup 1}H-{sup 15}N steady-state NOEs, and transverse cross-relaxation rates ({eta}{sub xy}) were obtained at 30 deg. C for all resolved backbone secondary amide groups using {sup 1} H-detected two-dimensional NMR experiments. Ratios of transverse auto and cross relaxation rates were used to identify NH groups influenced by slow conformational rearrangement. Relaxation data were fit to the extended model free dynamics formalism, yielding parameters describing axially symmetric molecular rotational diffusion and the internal dynamics of each NH group. The molecular rotational correlation time ({tau}{sub m}) is 5.09{+-}0.02 ns, indicating that eotaxin exists predominantly as a monomer under the conditions of the NMR study. The ratio of diffusion rates about unique and perpendicular axes (D{sub parallel}/D{sub perpendicular}) is 0.81{+-}0.02. Residues with large amplitudes of subnanosecond motion are clustered in the N-terminal region (residues 1-19), the C-terminus (residues 68-73) and the loop connecting the first two {beta}-strands (residues 30-37). N-terminal flexibility appears to be conserved throughout the chemokine family and may have implications for the mechanism of chemokine receptor activation. Residues exhibiting significant dynamics on the microsecond-millisecond time scale are located close to the two conserved disulfide bonds, suggesting that these motions may be coupled to disulfide bond isomerization.

A 3D-structural model of unsulfated chondroitin from high-field NMR: 4-sulfation has little effect on backbone conformation

Science.gov (United States)

Sattelle, Benedict M.; Shakeri, Javad; Roberts, Ian S.; Almond, Andrew

2010-01-01

The glycosaminoglycan chondroitin sulfate is essential in human health and disease but exactly how sulfation dictates its 3D-strucutre at the atomic level is unclear. To address this, we have purified homogenous oligosaccharides of unsulfated chondroitin (with and without 15N-enrichment) and analysed them by high-field NMR to make a comparison published chondroitin sulfate and hyaluronan 3D-structures. The result is the first full assignment of the tetrasaccharide and an experimental 3D-model of the hexasaccharide (PDB code 2KQO). In common with hyaluronan, we confirm that the amide proton is not involved in strong, persistent inter-residue hydrogen bonds. However, in contrast to hyaluronan, a hydrogen bond is not inferred between the hexosamine OH-4 and the glucuronic acid O5 atoms across the β(1→3) glycosidic linkage. The unsulfated chondroitin bond geometry differs slightly from hyaluronan by rotation about the β(1→3) ψ dihedral (as previously predicted by simulation), while the β(1→4) linkage is unaffected. Furthermore, comparison shows that this glycosidic linkage geometry is similar in chondroitin-4-sulfate. We therefore hypothesise that both hexosamine OH-4 and OH-6 atoms are solvent exposed in chondroitin, explaining why it is amenable to sulfation and hyaluronan is not, and also that 4-sulfation has little effect on backbone conformation. Our conclusions exemplify the value of the 3D-model presented here and progress our understanding of glycosaminoglycan molecular properties. PMID:20022001

Improved protein surface comparison and application to low-resolution protein structure data

Directory of Open Access Journals (Sweden)

Kihara Daisuke

2010-12-01

Full Text Available Abstract Background Recent advancements of experimental techniques for determining protein tertiary structures raise significant challenges for protein bioinformatics. With the number of known structures of unknown function expanding at a rapid pace, an urgent task is to provide reliable clues to their biological function on a large scale. Conventional approaches for structure comparison are not suitable for a real-time database search due to their slow speed. Moreover, a new challenge has arisen from recent techniques such as electron microscopy (EM, which provide low-resolution structure data. Previously, we have introduced a method for protein surface shape representation using the 3D Zernike descriptors (3DZDs. The 3DZD enables fast structure database searches, taking advantage of its rotation invariance and compact representation. The search results of protein surface represented with the 3DZD has showngood agreement with the existing structure classifications, but some discrepancies were also observed. Results The three new surface representations of backbone atoms, originally devised all-atom-surface representation, and the combination of all-atom surface with the backbone representation are examined. All representations are encoded with the 3DZD. Also, we have investigated the applicability of the 3DZD for searching protein EM density maps of varying resolutions. The surface representations are evaluated on structure retrieval using two existing classifications, SCOP and the CE-based classification. Conclusions Overall, the 3DZDs representing backbone atoms show better retrieval performance than the original all-atom surface representation. The performance further improved when the two representations are combined. Moreover, we observed that the 3DZD is also powerful in comparing low-resolution structures obtained by electron microscopy.

Improved protein surface comparison and application to low-resolution protein structure data.

Science.gov (United States)

Sael, Lee; Kihara, Daisuke

2010-12-14

Recent advancements of experimental techniques for determining protein tertiary structures raise significant challenges for protein bioinformatics. With the number of known structures of unknown function expanding at a rapid pace, an urgent task is to provide reliable clues to their biological function on a large scale. Conventional approaches for structure comparison are not suitable for a real-time database search due to their slow speed. Moreover, a new challenge has arisen from recent techniques such as electron microscopy (EM), which provide low-resolution structure data. Previously, we have introduced a method for protein surface shape representation using the 3D Zernike descriptors (3DZDs). The 3DZD enables fast structure database searches, taking advantage of its rotation invariance and compact representation. The search results of protein surface represented with the 3DZD has showngood agreement with the existing structure classifications, but some discrepancies were also observed. The three new surface representations of backbone atoms, originally devised all-atom-surface representation, and the combination of all-atom surface with the backbone representation are examined. All representations are encoded with the 3DZD. Also, we have investigated the applicability of the 3DZD for searching protein EM density maps of varying resolutions. The surface representations are evaluated on structure retrieval using two existing classifications, SCOP and the CE-based classification. Overall, the 3DZDs representing backbone atoms show better retrieval performance than the original all-atom surface representation. The performance further improved when the two representations are combined. Moreover, we observed that the 3DZD is also powerful in comparing low-resolution structures obtained by electron microscopy.

Mnn10 Maintains Pathogenicity in Candida albicans by Extending α-1,6-Mannose Backbone to Evade Host Dectin-1 Mediated Antifungal Immunity.

Directory of Open Access Journals (Sweden)

Shi Qun Zhang

2016-05-01

Full Text Available The cell wall is a dynamic structure that is important for the pathogenicity of Candida albicans. Mannan, which is located in the outermost layer of the cell wall, has been shown to contribute to the pathogenesis of C. albicans, however, the molecular mechanism by which this occurs remains unclear. Here we identified a novel α-1,6-mannosyltransferase encoded by MNN10 in C. albicans. We found that Mnn10 is required for cell wall α-1,6-mannose backbone biosynthesis and polysaccharides organization. Deletion of MNN10 resulted in significant attenuation of the pathogenesis of C. albicans in a murine systemic candidiasis model. Inhibition of α-1,6-mannose backbone extension did not, however, impact the invasive ability of C. albicans in vitro. Notably, mnn10 mutant restored the invasive capacity in athymic nude mice, which further supports the notion of an enhanced host antifungal defense related to this backbone change. Mnn10 mutant induced enhanced Th1 and Th17 cell mediated antifungal immunity, and resulted in enhanced recruitment of neutrophils and monocytes for pathogen clearance in vivo. We also demonstrated that MNN10 could unmask the surface β-(1,3-glucan, a crucial pathogen-associated molecular pattern (PAMP of C. albicans recognized by host Dectin-1. Our results demonstrate that mnn10 mutant could stimulate an enhanced Dectin-1 dependent immune response of macrophages in vitro, including the activation of nuclear factor-κB, mitogen-activated protein kinase pathways, and secretion of specific cytokines such as TNF-α, IL-6, IL-1β and IL-12p40. In summary, our study indicated that α-1,6-mannose backbone is critical for the pathogenesis of C. albicans via shielding β-glucan from recognition by host Dectin-1 mediated immune recognition. Moreover, our work suggests that inhibition of α-1,6-mannose extension by Mnn10 may represent a novel modality to reduce the pathogenicity of C. albicans.

Robustness and backbone motif of a cancer network regulated by miR-17-92 cluster during the G1/S transition.

Directory of Open Access Journals (Sweden)

Lijian Yang

Full Text Available Based on interactions among transcription factors, oncogenes, tumor suppressors and microRNAs, a Boolean model of cancer network regulated by miR-17-92 cluster is constructed, and the network is associated with the control of G1/S transition in the mammalian cell cycle. The robustness properties of this regulatory network are investigated by virtue of the Boolean network theory. It is found that, during G1/S transition in the cell cycle process, the regulatory networks are robustly constructed, and the robustness property is largely preserved with respect to small perturbations to the network. By using the unique process-based approach, the structure of this network is analyzed. It is shown that the network can be decomposed into a backbone motif which provides the main biological functions, and a remaining motif which makes the regulatory system more stable. The critical role of miR-17-92 in suppressing the G1/S cell cycle checkpoint and increasing the uncontrolled proliferation of the cancer cells by targeting a genetic network of interacting proteins is displayed with our model.

Treatment Results of Injuries of Thoracic and Lumbar Backbone Departments at Osteoporosis Patients

Directory of Open Access Journals (Sweden)

D.Y. Sumin

2009-06-01

Full Text Available Information relates to radiologic (computer tomography manifestations providing the visualization of thoracic and lumbar backbone department injuries at osteoporotic patients. Contemporary methods of transcutaneous and trans-pedicle vertebroplasty with bone cement allows to obtain a stable positive healing effect against such pathologies.

The DNA and RNA sugar-phosphate backbone emerges as the key player. An overview of quantum-chemical, structural biology and simulation studies

Czech Academy of Sciences Publication Activity Database

Šponer, Jiří; Mládek, Arnošt; Šponer, Judit E.; Svozil, Daniel; Zgarbová, M.; Banáš, Pavel; Jurečka, P.; Otyepka, M.

2012-01-01

Roč. 14, č. 44 (2012), s. 15257-15277 ISSN 1463-9076 R&D Projects: GA ČR(CZ) GD203/09/H046; GA ČR(CZ) GAP208/10/2302; GA ČR(CZ) GAP208/11/1822; GA ČR(CZ) GAP208/12/1878; GA ČR(CZ) GA203/09/1476; GA ČR(CZ) GBP305/12/G034 Institutional research plan: CEZ:AV0Z50040702 Keywords : DNA * RNA * sugar-phosphate backbone Subject RIV: BO - Biophysics Impact factor: 3.829, year: 2012

An Enhanced Backbone-Assisted Reliable Framework for Wireless Sensor Networks

Directory of Open Access Journals (Sweden)

Amna Ali

2010-03-01

Full Text Available An extremely reliable source to sink communication is required for most of the contemporary WSN applications especially pertaining to military, healthcare and disaster-recovery. However, due to their intrinsic energy, bandwidth and computational constraints, Wireless Sensor Networks (WSNs encounter several challenges in reliable source to sink communication. In this paper, we present a novel reliable topology that uses reliable hotlines between sensor gateways to boost the reliability of end-to-end transmissions. This reliable and efficient routing alternative reduces the number of average hops from source to the sink. We prove, with the help of analytical evaluation, that communication using hotlines is considerably more reliable than traditional WSN routing. We use reliability theory to analyze the cost and benefit of adding gateway nodes to a backbone-assisted WSN. However, in hotline assisted routing some scenarios where source and the sink are just a couple of hops away might bring more latency, therefore, we present a Signature Based Routing (SBR scheme. SBR enables the gateways to make intelligent routing decisions, based upon the derived signature, hence providing lesser end-to-end delay between source to the sink communication. Finally, we evaluate our proposed hotline based topology with the help of a simulation tool and show that the proposed topology provides manifold increase in end-to-end reliability.

Life estimation and analysis of dielectric strength, hydrocarbon backbone and oxidation of high voltage multi stressed EPDM composites

Science.gov (United States)

Khattak, Abraiz; Amin, Muhammad; Iqbal, Muhammad; Abbas, Naveed

2018-02-01

Micro and nanocomposites of ethylene propylene diene monomer (EPDM) are recently studied for different characteristics. Study on life estimation and effects of multiple stresses on its dielectric strength and backbone scission and oxidation is also vital for endorsement of these composites for high voltage insulation and other outdoor applications. In order to achieve these goals, unfilled EPDM and its micro and nanocomposites are prepared at 23 phr micro silica and 6 phr nanosilica loadings respectively. Prepared samples are energized at 2.5 kV AC voltage and subjected for a long time to heat, ultraviolet radiation, acid rain, humidity and salt fog in accelerated manner in laboratory. Dielectric strength, leakage current and intensity of saturated backbone and carbonyl group are periodically measured. Loss in dielectric strength, increase in leakage current and backbone degradation and oxidation were observed in all samples. These effects were least in the case of EPDM nanocomposite. The nanocomposite sample also demonstrated longest shelf life.

Quantum Chemical Benchmark Study on 46 RNA Backbone Families Using a Dinucleotide Unit

Czech Academy of Sciences Publication Activity Database

Kruse, H.; Mládek, Arnošt; Gkionis, Konstantinos; Hansen, A.; Grimme, S.; Šponer, Jiří

2015-01-01

Roč. 11, č. 10 (2015), s. 4972-4991 ISSN 1549-9618 R&D Projects: GA ČR(CZ) GBP305/12/G034 Institutional support: RVO:68081707 Keywords : MOLECULAR-DYNAMICS SIMULATIONS * DENSITY-FUNCTIONAL THEORY * SUGAR-PHOSPHATE BACKBONE Subject RIV: BO - Biophysics Impact factor: 5.301, year: 2015

Identifying secondary structures in proteins using NMR chemical shift 3D correlation maps

Science.gov (United States)

Kumari, Amrita; Dorai, Kavita

2013-06-01

NMR chemical shifts are accurate indicators of molecular environment and have been extensively used as aids in protein structure determination. This work focuses on creating empirical 3D correlation maps of backbone chemical shift nuclei for use as identifiers of secondary structure elements in proteins. A correlated database of backbone nuclei chemical shifts was constructed from experimental structural data gathered from entries in the Protein Data Bank (PDB) as well as isotropic chemical shift values from the RefDB database. Rigorous statistical analysis of the maps led to the conclusion that specific correlations between triplets of backbone chemical shifts are best able to differentiate between different secondary structures such as α-helices, β-strands and turns. The method is compared with similar techniques that use NMR chemical shift information as aids in biomolecular structure determination and performs well in tests done on experimental data determined for different types of proteins, including large multi-domain proteins and membrane proteins.

Mars - robust automatic backbone assignment of proteins

International Nuclear Information System (INIS)

Jung, Young-Sang; Zweckstetter, Markus

2004-01-01

MARS a program for robust automatic backbone assignment of 13 C/ 15 N labeled proteins is presented. MARS does not require tight thresholds for establishing sequential connectivity or detailed adjustment of these thresholds and it can work with a wide variety of NMR experiments. Using only 13 C α / 13 C β connectivity information, MARS allows automatic, error-free assignment of 96% of the 370-residue maltose-binding protein. MARS can successfully be used when data are missing for a substantial portion of residues or for proteins with very high chemical shift degeneracy such as partially or fully unfolded proteins. Other sources of information, such as residue specific information or known assignments from a homologues protein, can be included into the assignment process. MARS exports its result in SPARKY format. This allows visual validation and integration of automated and manual assignment

Improving VANETs Connectivity with a Totally Ad Hoc Living Mobile Backbone

Directory of Open Access Journals (Sweden)

Joilson Alves Junior

2015-01-01

Full Text Available The vehicular ad hoc network (VANET for intelligent transportation systems is an emerging concept to improve transportation security, reliability, and management. The network behavior can be totally different in topological aspects because of the mobility of vehicular nodes. The topology can be fully connected when the flow of vehicles is high and may have low connectivity or be invalid when the flow of vehicles is low or unbalanced. In big cities, the metropolitan buses that travel on exclusive lanes may be used to set up a metropolitan vehicular data network (backbone, raising the connectivity among the vehicles. Therefore, this paper proposes the implementation of a living mobile backbone, totally ad hoc (MOB-NET, which will provide infrastructure and raise the network connectivity. In order to show the viability of MOB-NET, statistical analyses were made with real data of express buses that travel through exclusive lanes, besides evaluations through simulations and analytic models. The statistic, analytic, and simulation results prove that the buses that travel through exclusive lanes can be used to build a communication network totally ad hoc and provide connectivity in more than 99% of the time, besides raising the delivery rate up to 95%.

Comparing the Reliability of Regular Topologies on a Backbone Network. A Case Study

DEFF Research Database (Denmark)

Cecilio, Sergio Labeage; Gutierrez Lopez, Jose Manuel; Riaz, M. Tahir

2009-01-01

The aim of this paper is to compare the reliability of regular topologies on a backbone network. The study is focused on a large-scale fiberoptic network. Different regular topological solutions as single ring, double ring or 4-Regular grid are applied to the case study, and compared in terms...

Design of an IPTV Multicast System for Internet Backbone Networks

Directory of Open Access Journals (Sweden)

T. H. Szymanski

2010-01-01

Full Text Available The design of an IPTV multicast system for the Internet backbone network is presented and explored through extensive simulations. In the proposed system, a resource reservation algorithm such as RSVP, IntServ, or DiffServ is used to reserve resources (i.e., bandwidth and buffer space in each router in an IP multicast tree. Each router uses an Input-Queued, Output-Queued, or Crosspoint-Queued switch architecture with unity speedup. A recently proposed Recursive Fair Stochastic Matrix Decomposition algorithm used to compute near-perfect transmission schedules for each IP router. The IPTV traffic is shaped at the sources using Application-Specific Token Bucker Traffic Shapers, to limit the burstiness of incoming network traffic. The IPTV traffic is shaped at the destinations using Application-Specific Playback Queues, to remove residual network jitter and reconstruct the original bursty IPTV video streams at each destination. All IPTV traffic flows are regenerated at the destinations with essentially zero delay jitter and essentially-perfect QoS. The destination nodes deliver the IPTV streams to the ultimate end users using the same IPTV multicast system over a regional Metropolitan Area Network. It is shown that all IPTV traffic is delivered with essentially-perfect end-to-end QoS, with deterministic bounds on the maximum delay and jitter on each video frame. Detailed simulations of an IPTV distribution system, multicasting several hundred high-definition IPTV video streams over several essentially saturated IP backbone networks are presented.

Gas separation performance of 6FDA-based polyimides with different chemical structures

KAUST Repository

Qiu, Wulin

2013-10-01

This work reports the gas separation performance of several 6FDA-based polyimides with different chemical structures, to correlate chemical structure with gas transport properties with a special focus on CO2 and CH 4 transport and plasticization stability of the polyimides membranes relevant to natural gas purification. The consideration of the other gases (He, O2 and N2) provided additional insights regarding effects of backbone structure on detailed penetrant properties. The polyimides studied include 6FDA-DAM, 6FDA-mPDA, 6FDA-DABA, 6FDA-DAM:DABA (3:2), 6FDA-DAM:mPDA (3:2) and 6FDA-mPDA:DABA (3:2). Both pure and binary gas permeation were investigated. The packing density, which is tunable by adjusting monomer type and composition of the various samples, correlated with transport permeability and selectivity. The separation performance of the polyimides for various gas pairs were also plotted for comparison to the upper bound curves, and it was found that this family of materials shows attractive performance. The CO 2 plasticization responses for the un-cross-linked polyimides showed good plasticization resistance to CO2/CH4 mixed gas with 10% CO2; however, only the cross-linked polyimides showed good plasticization resistance under aggressive gas feed conditions (CO 2/CH4 mixed gas with 50% CO2 or pure CO 2). For future work, asymmetric hollow fibers and carbon molecular sieve membranes based on the most attractive members of the family will be considered. © 2013 Elsevier Ltd. All rights reserved.

Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

Energy Technology Data Exchange (ETDEWEB)

Snodin, Benedict E. K., E-mail: benedict.snodin@chem.ox.ac.uk; Mosayebi, Majid; Schreck, John S.; Romano, Flavio; Doye, Jonathan P. K., E-mail: jonathan.doye@chem.ox.ac.uk [Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ (United Kingdom); Randisi, Ferdinando [Life Sciences Interface Doctoral Training Center, South Parks Road, Oxford OX1 3QU (United Kingdom); Rudolf Peierls Centre for Theoretical Physics, 1 Keble Road, Oxford OX1 3NP (United Kingdom); Šulc, Petr [Center for Studies in Physics and Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10065 (United States); Ouldridge, Thomas E. [Department of Mathematics, Imperial College, 180 Queen’s Gate, London SW7 2AZ (United Kingdom); Tsukanov, Roman; Nir, Eyal [Department of Chemistry and the Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer Sheva (Israel); Louis, Ard A. [Rudolf Peierls Centre for Theoretical Physics, 1 Keble Road, Oxford OX1 3NP (United Kingdom)

2015-06-21

We introduce an extended version of oxDNA, a coarse-grained model of deoxyribonucleic acid (DNA) designed to capture the thermodynamic, structural, and mechanical properties of single- and double-stranded DNA. By including explicit major and minor grooves and by slightly modifying the coaxial stacking and backbone-backbone interactions, we improve the ability of the model to treat large (kilobase-pair) structures, such as DNA origami, which are sensitive to these geometric features. Further, we extend the model, which was previously parameterised to just one salt concentration ([Na{sup +}] = 0.5M), so that it can be used for a range of salt concentrations including those corresponding to physiological conditions. Finally, we use new experimental data to parameterise the oxDNA potential so that consecutive adenine bases stack with a different strength to consecutive thymine bases, a feature which allows a more accurate treatment of systems where the flexibility of single-stranded regions is important. We illustrate the new possibilities opened up by the updated model, oxDNA2, by presenting results from simulations of the structure of large DNA objects and by using the model to investigate some salt-dependent properties of DNA.

Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

International Nuclear Information System (INIS)

Snodin, Benedict E. K.; Mosayebi, Majid; Schreck, John S.; Romano, Flavio; Doye, Jonathan P. K.; Randisi, Ferdinando; Šulc, Petr; Ouldridge, Thomas E.; Tsukanov, Roman; Nir, Eyal; Louis, Ard A.

2015-01-01

We introduce an extended version of oxDNA, a coarse-grained model of deoxyribonucleic acid (DNA) designed to capture the thermodynamic, structural, and mechanical properties of single- and double-stranded DNA. By including explicit major and minor grooves and by slightly modifying the coaxial stacking and backbone-backbone interactions, we improve the ability of the model to treat large (kilobase-pair) structures, such as DNA origami, which are sensitive to these geometric features. Further, we extend the model, which was previously parameterised to just one salt concentration ([Na + ] = 0.5M), so that it can be used for a range of salt concentrations including those corresponding to physiological conditions. Finally, we use new experimental data to parameterise the oxDNA potential so that consecutive adenine bases stack with a different strength to consecutive thymine bases, a feature which allows a more accurate treatment of systems where the flexibility of single-stranded regions is important. We illustrate the new possibilities opened up by the updated model, oxDNA2, by presenting results from simulations of the structure of large DNA objects and by using the model to investigate some salt-dependent properties of DNA

Geography-based structural analysis of the Internet

Energy Technology Data Exchange (ETDEWEB)

Kasiviswanathan, Shiva [Los Alamos National Laboratory; Eidenbenz, Stephan [Los Alamos National Laboratory; Yan, Guanhua [Los Alamos National Laboratory

2010-01-01

In this paper, we study some geographic aspects of the Internet. We base our analysis on a large set of geolocated IP hop-level session data (including about 300,000 backbone routers, 150 million end hosts, and 1 billion sessions) that we synthesized from a variety of different input sources such as US census data, computer usage statistics, Internet market share data, IP geolocation data sets, CAJDA's Skitter data set for backbone connectivity, and BGP routing tables. We use this model to perform a nationwide and statewide geographic analysis of the Internet. Our main observations are: (1) There is a dominant coast-to-coast pattern in the US Internet traffic. In fact, in many instances even if the end-devices are not near either coast, still the traffic between them takes a long detour through the coasts. (2) More than half of the Internet paths are inflated by 100% or more compared to their corresponding geometric straight-line distance. This circuitousness makes the average ratio between the routing distance and geometric distance big (around 10). (3) The weighted mean hop count is around 5, but the hop counts are very loosely correlated with the distances. The weighted mean AS count (number of ASes traversed) is around 3. (4) The AS size and the AS location number distributions are heavy-tailed and strongly correlated. Most of the ASes are medium sized and there is a wide variability in the geographic dispersion size (measured in terms of the convex hull area) of these ASes.

Tritium containing polymers having a polymer backbone substantially void of tritium

Science.gov (United States)

Jensen, G.A.; Nelson, D.A.; Molton, P.M.

1992-03-31

A radioluminescent light source comprises a solid mixture of a phosphorescent substance and a tritiated polymer. The solid mixture forms a solid mass having length, width, and thickness dimensions, and is capable of self-support. In one aspect of the invention, the phosphorescent substance comprises solid phosphor particles supported or surrounded within a solid matrix by a tritium containing polymer. The tritium containing polymer comprises a polymer backbone which is essentially void of tritium. 2 figs.

NMR structure of the N-terminal domain of the replication initiator protein DnaA

Energy Technology Data Exchange (ETDEWEB)

Wemmer, David E.; Lowery, Thomas J.; Pelton, Jeffrey G.; Chandonia, John-Marc; Kim, Rosalind; Yokota, Hisao; Wemmer, David E.

2007-08-07

DnaA is an essential component in the initiation of bacterial chromosomal replication. DnaA binds to a series of 9 base pair repeats leading to oligomerization, recruitment of the DnaBC helicase, and the assembly of the replication fork machinery. The structure of the N-terminal domain (residues 1-100) of DnaA from Mycoplasma genitalium was determined by NMR spectroscopy. The backbone r.m.s.d. for the first 86 residues was 0.6 +/- 0.2 Angstrom based on 742 NOE, 50 hydrogen bond, 46 backbone angle, and 88 residual dipolar coupling restraints. Ultracentrifugation studies revealed that the domain is monomeric in solution. Features on the protein surface include a hydrophobic cleft flanked by several negative residues on one side, and positive residues on the other. A negatively charged ridge is present on the opposite face of the protein. These surfaces may be important sites of interaction with other proteins involved in the replication process. Together, the structure and NMR assignments should facilitate the design of new experiments to probe the protein-protein interactions essential for the initiation of DNA replication.

Backbone resonance assignments for G protein α(i3) subunit in the GDP-bound state.

Science.gov (United States)

Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

2014-10-01

Guanine-nucleotide binding proteins (G proteins) serve as molecular switches in signaling pathways, by coupling the activation of G protein-coupled receptors (GPCRs) at the cell surface to intracellular responses. In the resting state, G protein forms a heterotrimer, consisting of the G protein α subunit with GDP (Gα·GDP) and the G protein βγ subunit (Gβγ). Ligand binding to GPCRs promotes the GDP-GTP exchange on Gα, leading to the dissociation of the GTP-bound form of Gα (Gα·GTP) and Gβγ. Then, Gα·GTP and Gβγ bind to their downstream effector enzymes or ion channels and regulate their activities, leading to a variety of cellular responses. Finally, Gα hydrolyzes the bound GTP to GDP and returns to the resting state by re-associating with Gβγ. The G proteins are classified with four major families based on the amino acid sequences of Gα: i/o, s, q/11, and 12/13. Here, we established the backbone resonance assignments of human Gαi3, a member of the i/o family with a molecular weight of 41 K, in complex with GDP. The chemical shifts were compared with those of Gα(i3) in complex with a GTP-analogue, GTPγS, which we recently reported, indicating that the residues with significant chemical shift differences are mostly consistent with the regions with the structural differences between the GDP- and GTPγS-bound states, as indicated in the crystal structures. The assignments of Gα(i3)·GDP would be useful for the analyses of the dynamics of Gα(i3) and its interactions with various target molecules.

Extracting the information backbone in online system.

Directory of Open Access Journals (Sweden)

Qian-Ming Zhang

Full Text Available Information overload is a serious problem in modern society and many solutions such as recommender system have been proposed to filter out irrelevant information. In the literature, researchers have been mainly dedicated to improving the recommendation performance (accuracy and diversity of the algorithms while they have overlooked the influence of topology of the online user-object bipartite networks. In this paper, we find that some information provided by the bipartite networks is not only redundant but also misleading. With such "less can be more" feature, we design some algorithms to improve the recommendation performance by eliminating some links from the original networks. Moreover, we propose a hybrid method combining the time-aware and topology-aware link removal algorithms to extract the backbone which contains the essential information for the recommender systems. From the practical point of view, our method can improve the performance and reduce the computational time of the recommendation system, thus improving both of their effectiveness and efficiency.

Extracting the information backbone in online system.

Science.gov (United States)

Zhang, Qian-Ming; Zeng, An; Shang, Ming-Sheng

2013-01-01

Information overload is a serious problem in modern society and many solutions such as recommender system have been proposed to filter out irrelevant information. In the literature, researchers have been mainly dedicated to improving the recommendation performance (accuracy and diversity) of the algorithms while they have overlooked the influence of topology of the online user-object bipartite networks. In this paper, we find that some information provided by the bipartite networks is not only redundant but also misleading. With such "less can be more" feature, we design some algorithms to improve the recommendation performance by eliminating some links from the original networks. Moreover, we propose a hybrid method combining the time-aware and topology-aware link removal algorithms to extract the backbone which contains the essential information for the recommender systems. From the practical point of view, our method can improve the performance and reduce the computational time of the recommendation system, thus improving both of their effectiveness and efficiency.

Extracting the Information Backbone in Online System

Science.gov (United States)

Zhang, Qian-Ming; Zeng, An; Shang, Ming-Sheng

2013-01-01

Information overload is a serious problem in modern society and many solutions such as recommender system have been proposed to filter out irrelevant information. In the literature, researchers have been mainly dedicated to improving the recommendation performance (accuracy and diversity) of the algorithms while they have overlooked the influence of topology of the online user-object bipartite networks. In this paper, we find that some information provided by the bipartite networks is not only redundant but also misleading. With such “less can be more” feature, we design some algorithms to improve the recommendation performance by eliminating some links from the original networks. Moreover, we propose a hybrid method combining the time-aware and topology-aware link removal algorithms to extract the backbone which contains the essential information for the recommender systems. From the practical point of view, our method can improve the performance and reduce the computational time of the recommendation system, thus improving both of their effectiveness and efficiency. PMID:23690946

Backbone resonance assignments of the outer membrane lipoprotein FrpD from Neisseria meningitidis

Czech Academy of Sciences Publication Activity Database

Bumba, Ladislav; Sviridova, E.; Kutá-Smatanová, Ivana; Řezáčová, Pavlína; Veverka, Václav

2014-01-01

Roč. 8, č. 1 (2014), s. 53-55 ISSN 1874-2718 R&D Projects: GA ČR(CZ) GAP207/11/0717; GA MŠk(CZ) LK11205 Institutional support: RVO:61388963 ; RVO:61388971 ; RVO:67179843 Keywords : Neisseria meningitidis * FrpC * FrpD * backbone assignments * NMR * iron-regulated protein Subject RIV: CE - Biochemistry Impact factor: 0.760, year: 2014

Probing adenine rings and backbone linkages using base specific isotope-edited Raman spectroscopy: application to group II intron ribozyme domain V.

Science.gov (United States)

Chen, Yuanyuan; Eldho, Nadukkudy V; Dayie, T Kwaku; Carey, Paul R

2010-04-27

Raman difference spectroscopy is used to probe the properties of a 36-nt RNA molecule, "D5", which lies at the heart of the catalytic apparatus in group II introns. For D5 that has all of its adenine residues labeled with (13)C and (15)N and utilizing Raman difference spectroscopy, we identify the conformationally sensitive -C-O-P-O-C- stretching modes of the unlabeled bonds adjacent to adenine bases, as well as the adenine ring modes themselves. The phosphodiester modes can be assigned to individual adenine residues based on earlier NMR data. The effect of Mg(2+) binding was explored by analyzing the Raman difference spectra for [D5 + Mg(2+)] minus [D5 no Mg(2+)], for D5 unlabeled, or D5 labeled with (13)C/(15)N-enriched adenine. In both sets of data we assign differential features to G ring modes perturbed by Mg(2+) binding at the N7 position. In the A-labeled spectra we attribute a Raman differential near 1450 cm(-1) and changes of intensity at 1296 cm(-1) to Mg binding at the N7 position of adenine bases. The A and G bases involved in Mg(2+) binding again can be identified using earlier NMR results. For the unlabeled D5, a change in the C-O-P-O-C stretch profile at 811 cm(-1) upon magnesium binding is due to a "tightening up" (in the sense of a more rigid molecule with less dynamic interchange among competing ribose conformers) of the D5 structure. For adenine-labeled D5, small changes in the adenine backbone bond signatures in the 810-830 cm(-1) region suggest that small conformational changes occur in the tetraloop and bulge regions upon binding of Mg(2+). The PO(2)(-) stretching vibration, near 1100 cm(-1), from the nonbridging phosphate groups, probes the effect of Mg(2+)-hydrate inner-sphere interactions that cause an upshift. In turn, the upshift is modulated by the presence of monovalent cations since in the presence of Na(+) and Li(+) the upshift is 23 +/- 2 cm(-1) while in the presence of K(+) and Cs(+) it is 13 +/- 3 cm(-1), a finding that correlates

Mechanical reliability of porous low-k dielectrics for advanced interconnect: Study of the instability mechanisms in porous low-k dielectrics and their mediation through inert plasma induced re-polymerization of the backbone structure

Science.gov (United States)

Sa, Yoonki

siloxane backbone structure under 300˜400°C by reaction with -OH, and simultaneously creating a new Si-O-Si crosslink. As an alternative way of increasing the thermo-mechanical reliability, PLK dielectric film with an intrinsically robust structure by controlling pore morphology is fabricated. Since pore surface is susceptible to be damaged by BEOL integration damage, pore morphology in terms of size, distribution, and connectivity should be controlled in order to increase the robustness of PLK dielectrics. Generally, pores in PLK matrix are created by depositing organic fragment (called 'porogen') into the film and removed later by thermal and electron beam cure to form porous PLK layer (; Subtractive deposition). However, during the curing Si-O-Si backbone crosslink is broken and pores are easily interconnected, leading to vulnerable structure to the extrinsic damage. Constitutive deposition approach is feasible for the introduction of smaller nano-pores with little or no interconnectivity by steric hindrance. Due to the closed pore system, thermally-induced stress and plasma-induced damage is restricted merely to the surface of the dielectric film. This is attributed to the stable siloxane (Si-O-Si) backbone and the terminally bonded methyl group attached to silicon (Si-CH3), inducing steric hindrance that lowers the density of the films. The low dielectric constant and mechanical stability are closely involved with the formation of the Si-O-Si cage-like structure and an appropriate combination of stable Si-O-Si, Si-CH3 groups. Based on the FTIR and XPS spectra, it is concluded that the formation of the Si-O-Si cage-like structure was enhanced by structural method. It is believed that all these changes are beneficial for improving PLK stability as will be detailed in this dissertation. Especially, the originality and particular advantage of this study regarding plasma-induced damage repair will be highlighted.

The backbone of the post-synaptic density originated in a unicellular ancestor of choanoflagellates and metazoans

Directory of Open Access Journals (Sweden)

Manuel Michaël

2010-02-01

Full Text Available Abstract Background Comparative genomics of the early diverging metazoan lineages and of their unicellular sister-groups opens new window to reconstructing the genetic changes which preceded or accompanied the evolution of multicellular body plans. A recent analysis found that the genome of the nerve-less sponges encodes the homologues of most vertebrate post-synaptic proteins. In vertebrate excitatory synapses, these proteins assemble to form the post-synaptic density, a complex molecular platform linking membrane receptors, components of their signalling pathways, and the cytoskeleton. Newly available genomes from Monosiga brevicollis (a member of Choanoflagellata, the closest unicellular relatives of animals and Trichoplax adhaerens (a member of Placozoa: besides sponges, the only nerve-less metazoans offer an opportunity to refine our understanding of post-synaptic protein evolution. Results Searches for orthologous proteins and reconstruction of gene gains/losses based on the taxon phylogeny indicate that post-synaptic proteins originated in two main steps. The backbone scaffold proteins (Shank, Homer, DLG and some of their partners were acquired in a unicellular ancestor of choanoflagellates and metazoans. A substantial additional set appeared in an exclusive ancestor of the Metazoa. The placozoan genome contains most post-synaptic genes but lacks some of them. Notably, the master-scaffold protein Shank might have been lost secondarily in the placozoan lineage. Conclusions The time of origination of most post-synaptic proteins was not concomitant with the acquisition of synapses or neural-like cells. The backbone of the scaffold emerged in a unicellular context and was probably not involved in cell-cell communication. Based on the reconstructed protein composition and potential interactions, its ancestral function could have been to link calcium signalling and cytoskeleton regulation. The complex later became integrated into the evolving

Interplay between Peptide Bond Geometrical Parameters in Nonglobular Structural Contexts

OpenAIRE

Esposito, Luciana; Balasco, Nicole; De Simone, Alfonso; Berisio, Rita; Vitagliano, Luigi

2013-01-01

Several investigations performed in the last two decades have unveiled that geometrical parameters of protein backbone show a remarkable variability. Although these studies have provided interesting insights into one of the basic aspects of protein structure, they have been conducted on globular and water-soluble proteins. We report here a detailed analysis of backbone geometrical parameters in nonglobular proteins/peptides. We considered membrane proteins and two distinct fibrous systems (am...

1H and 15N NMR assignment and solution structure of the SH3 domain of spectrin: Comparison of unrefined and refined structure sets with the crystal structure

International Nuclear Information System (INIS)

Blanco, Francisco J.; Ortiz, Angel R.; Serrano, Luis

1997-01-01

The assignment of the 1 H and 15 Nnuclear magnetic resonance spectra of the Src-homology region 3 domain of chicken brain α-spectrin has been obtained. A set of solution structures has been determined from distance and dihedral angle restraints,which provide a reasonable representation of the protein structure in solution, as evaluated by a principal component analysis of the global pairwise root-mean-square deviation (rmsd) in a large set of structures consisting of the refined and unrefined solution structures and the crystal structure. The solution structure is well defined, with a lower degree of convergence between the structures in the loop regions than in the secondary structure elements. The average pairwise rmsd between the 15 refined solution structures is 0.71 ± 0.13 A for the backbone atoms and 1.43 ± 0.14 A for all heavy atoms. The solution structure is basically the same as the crystal structure. The average rmsd between the 15 refined solution structures and the crystal structure is 0.76 A for the backbone atoms and 1.45 ± 0.09 A for all heavy atoms. There are, however, small differences probably caused by intermolecular contacts in the crystal structure

Chemical crosslinking and mass spectrometry studies of the structure and dynamics of membrane proteins and receptors.

Energy Technology Data Exchange (ETDEWEB)

Haskins, William E.; Leavell, Michael D.; Lane, Pamela; Jacobsen, Richard B.; Hong, Joohee; Ayson, Marites J.; Wood, Nichole L.; Schoeniger, Joseph S.; Kruppa, Gary Hermann; Sale, Kenneth L.; Young, Malin M.; Novak, Petr

2005-03-01

Membrane proteins make up a diverse and important subset of proteins for which structural information is limited. In this study, chemical cross-linking and mass spectrometry were used to explore the structure of the G-protein-coupled photoreceptor bovine rhodopsin in the dark-state conformation. All experiments were performed in rod outer segment membranes using amino acid 'handles' in the native protein sequence and thus minimizing perturbations to the native protein structure. Cysteine and lysine residues were covalently cross-linked using commercially available reagents with a range of linker arm lengths. Following chemical digestion of cross-linked protein, cross-linked peptides were identified by accurate mass measurement using liquid chromatography-fourier transform mass spectrometry and an automated data analysis pipeline. Assignments were confirmed and, if necessary, resolved, by tandem MS. The relative reactivity of lysine residues participating in cross-links was evaluated by labeling with NHS-esters. A distinct pattern of cross-link formation within the C-terminal domain, and between loop I and the C-terminal domain, emerged. Theoretical distances based on cross-linking were compared to inter-atomic distances determined from the energy-minimized X-ray crystal structure and Monte Carlo conformational search procedures. In general, the observed cross-links can be explained by re-positioning participating side-chains without significantly altering backbone structure. One exception, between C3 16 and K325, requires backbone motion to bring the reactive atoms into sufficient proximity for cross-linking. Evidence from other studies suggests that residues around K325 for a region of high backbone mobility. These findings show that cross-linking studies can provide insight into the structural dynamics of membrane proteins in their native environment.

Large-scale phylogenomic analysis resolves a backbone phylogeny in ferns

Science.gov (United States)

Shen, Hui; Jin, Dongmei; Shu, Jiang-Ping; Zhou, Xi-Le; Lei, Ming; Wei, Ran; Shang, Hui; Wei, Hong-Jin; Zhang, Rui; Liu, Li; Gu, Yu-Feng; Zhang, Xian-Chun; Yan, Yue-Hong

2018-01-01

Abstract Background Ferns, originated about 360 million years ago, are the sister group of seed plants. Despite the remarkable progress in our understanding of fern phylogeny, with conflicting molecular evidence and different morphological interpretations, relationships among major fern lineages remain controversial. Results With the aim to obtain a robust fern phylogeny, we carried out a large-scale phylogenomic analysis using high-quality transcriptome sequencing data, which covered 69 fern species from 38 families and 11 orders. Both coalescent-based and concatenation-based methods were applied to both nucleotide and amino acid sequences in species tree estimation. The resulting topologies are largely congruent with each other, except for the placement of Angiopteris fokiensis, Cheiropleuria bicuspis, Diplaziopsis brunoniana, Matteuccia struthiopteris, Elaphoglossum mcclurei, and Tectaria subpedata. Conclusions Our result confirmed that Equisetales is sister to the rest of ferns, and Dennstaedtiaceae is sister to eupolypods. Moreover, our result strongly supported some relationships different from the current view of fern phylogeny, including that Marattiaceae may be sister to the monophyletic clade of Psilotaceae and Ophioglossaceae; that Gleicheniaceae and Hymenophyllaceae form a monophyletic clade sister to Dipteridaceae; and that Aspleniaceae is sister to the rest of the groups in eupolypods II. These results were interpreted with morphological traits, especially sporangia characters, and a new evolutionary route of sporangial annulus in ferns was suggested. This backbone phylogeny in ferns sets a foundation for further studies in biology and evolution in ferns, and therefore in plants. PMID:29186447

Large-scale phylogenomic analysis resolves a backbone phylogeny in ferns.

Science.gov (United States)

Shen, Hui; Jin, Dongmei; Shu, Jiang-Ping; Zhou, Xi-Le; Lei, Ming; Wei, Ran; Shang, Hui; Wei, Hong-Jin; Zhang, Rui; Liu, Li; Gu, Yu-Feng; Zhang, Xian-Chun; Yan, Yue-Hong

2018-02-01

Ferns, originated about 360 million years ago, are the sister group of seed plants. Despite the remarkable progress in our understanding of fern phylogeny, with conflicting molecular evidence and different morphological interpretations, relationships among major fern lineages remain controversial. With the aim to obtain a robust fern phylogeny, we carried out a large-scale phylogenomic analysis using high-quality transcriptome sequencing data, which covered 69 fern species from 38 families and 11 orders. Both coalescent-based and concatenation-based methods were applied to both nucleotide and amino acid sequences in species tree estimation. The resulting topologies are largely congruent with each other, except for the placement of Angiopteris fokiensis, Cheiropleuria bicuspis, Diplaziopsis brunoniana, Matteuccia struthiopteris, Elaphoglossum mcclurei, and Tectaria subpedata. Our result confirmed that Equisetales is sister to the rest of ferns, and Dennstaedtiaceae is sister to eupolypods. Moreover, our result strongly supported some relationships different from the current view of fern phylogeny, including that Marattiaceae may be sister to the monophyletic clade of Psilotaceae and Ophioglossaceae; that Gleicheniaceae and Hymenophyllaceae form a monophyletic clade sister to Dipteridaceae; and that Aspleniaceae is sister to the rest of the groups in eupolypods II. These results were interpreted with morphological traits, especially sporangia characters, and a new evolutionary route of sporangial annulus in ferns was suggested. This backbone phylogeny in ferns sets a foundation for further studies in biology and evolution in ferns, and therefore in plants. © The Authors 2017. Published by Oxford University Press.

The Three-Dimensional Solution Structure of the Src Homology Domain-2 of the Growth Factor Receptor-Bound Protein-2

International Nuclear Information System (INIS)

Senior, Mary M.; Frederick, Anne F.; Black, Stuart; Murgolo, Nicholas J.; Perkins, Louise M.; Wilson, Oswald; Snow, Mark E.; Wang Yusen

1998-01-01

A set of high-resolution three-dimensional solution structures of the Src homology region-2 (SH2) domain of the growth factor receptor-bound protein-2 was determined using heteronuclear NMR spectroscopy. The NMR data used in this study were collected on a stable monomeric protein solution that was free of protein aggregates and proteolysis. The solution structure was determined based upon a total of 1439 constraints, which included 1326 nuclear Overhauser effect distance constraints, 70 hydrogen bond constraints, and 43 dihedral angle constraints. Distance geometry-simulated annealing calculations followed by energy minimization yielded a family of 18 structures that converged to a root-mean-square deviation of 1.09 A for all backbone atoms and 0.40 A for the backbone atoms of the central β-sheet. The core structure of the SH2 domain contains an antiparallel β-sheet flanked by two parallel α-helices displaying an overall architecture that is similar to other known SH2 domain structures. This family of NMR structures is compared to the X-ray structure and to another family of NMR solution structures determined under different solution conditions

UV-POSIT: Web-Based Tools for Rapid and Facile Structural Interpretation of Ultraviolet Photodissociation (UVPD) Mass Spectra

Science.gov (United States)

Rosenberg, Jake; Parker, W. Ryan; Cammarata, Michael B.; Brodbelt, Jennifer S.

2018-04-01

UV-POSIT (Ultraviolet Photodissociation Online Structure Interrogation Tools) is a suite of web-based tools designed to facilitate the rapid interpretation of data from native mass spectrometry experiments making use of 193 nm ultraviolet photodissociation (UVPD). The suite includes four separate utilities which assist in the calculation of fragment ion abundances as a function of backbone cleavage sites and sequence position; the localization of charge sites in intact proteins; the calculation of hydrogen elimination propensity for a-type fragment ions; and mass-offset searching of UVPD spectra to identify unknown modifications and assess false positive fragment identifications. UV-POSIT is implemented as a Python/Flask web application hosted at http://uv-posit.cm.utexas.edu. UV-POSIT is available under the MIT license, and the source code is available at https://github.com/jarosenb/UV_POSIT. [Figure not available: see fulltext.

UV-POSIT: Web-Based Tools for Rapid and Facile Structural Interpretation of Ultraviolet Photodissociation (UVPD) Mass Spectra.

Science.gov (United States)

Rosenberg, Jake; Parker, W Ryan; Cammarata, Michael B; Brodbelt, Jennifer S

2018-04-06

UV-POSIT (Ultraviolet Photodissociation Online Structure Interrogation Tools) is a suite of web-based tools designed to facilitate the rapid interpretation of data from native mass spectrometry experiments making use of 193 nm ultraviolet photodissociation (UVPD). The suite includes four separate utilities which assist in the calculation of fragment ion abundances as a function of backbone cleavage sites and sequence position; the localization of charge sites in intact proteins; the calculation of hydrogen elimination propensity for a-type fragment ions; and mass-offset searching of UVPD spectra to identify unknown modifications and assess false positive fragment identifications. UV-POSIT is implemented as a Python/Flask web application hosted at http://uv-posit.cm.utexas.edu . UV-POSIT is available under the MIT license, and the source code is available at https://github.com/jarosenb/UV_POSIT . Graphical Abstract.

Role of monomer sequence and backbone chemistry in polypeptoid copolymers for marine antifouling coatings

Science.gov (United States)

Patterson, Anastasia; Wenning, Brandon; Rizis, Georgios; Calabrese, David; Finlay, John; Franco, Sofia; Clare, Anthony; Kramer, Edward; Ober, Christopher; Segalman, Rachel

The design rules elucidated in this work suggest that antifouling coatings bearing pendant peptoid side chains perform better overall in marine fouling tests than those with peptide side chains, with extremely low attachment of N. incerta and high removal of U. linza. This difference in performance is likely due to the lack of a hydrogen bond donor in the peptoid backbone. Furthermore, we show that the bulk polymer material of these hierarchical coatings (based on PEO or PDMS) plays a key role in determining both surface presentation and fouling release performance. We demonstrate these trends utilizing a modular coating based on a triblock copolymer consisting of polystyrene and a vinyl-containing midblock, to which sequence-defined pendant oligomers (peptides or peptoids with sequences of oligo-PEO and fluoroalkyl groups) are attached via thiol-ene ``click'' chemistry. Surface presentation was analyzed with X-ray photoelectron spectroscopy and captive bubble water contact angle, and antifouling performance was evaluated with attachment and removal bioassays of the marine macroalga U. linza and diatom N. incerta. NSF GRFP and ONR PECASE.

Assessing protein conformational sampling methods based on bivariate lag-distributions of backbone angles

KAUST Repository

Maadooliat, Mehdi; Gao, Xin; Huang, Jianhua Z.

2012-01-01

Despite considerable progress in the past decades, protein structure prediction remains one of the major unsolved problems in computational biology. Angular-sampling-based methods have been extensively studied recently due to their ability to capture the continuous conformational space of protein structures. The literature has focused on using a variety of parametric models of the sequential dependencies between angle pairs along the protein chains. In this article, we present a thorough review of angular-sampling-based methods by assessing three main questions: What is the best distribution type to model the protein angles? What is a reasonable number of components in a mixture model that should be considered to accurately parameterize the joint distribution of the angles? and What is the order of the local sequence-structure dependency that should be considered by a prediction method? We assess the model fits for different methods using bivariate lag-distributions of the dihedral/planar angles. Moreover, the main information across the lags can be extracted using a technique called Lag singular value decomposition (LagSVD), which considers the joint distribution of the dihedral/planar angles over different lags using a nonparametric approach and monitors the behavior of the lag-distribution of the angles using singular value decomposition. As a result, we developed graphical tools and numerical measurements to compare and evaluate the performance of different model fits. Furthermore, we developed a web-tool (http://www.stat.tamu. edu/~madoliat/LagSVD) that can be used to produce informative animations. © The Author 2012. Published by Oxford University Press.

Assessing protein conformational sampling methods based on bivariate lag-distributions of backbone angles

KAUST Repository

Maadooliat, Mehdi

2012-08-27

Despite considerable progress in the past decades, protein structure prediction remains one of the major unsolved problems in computational biology. Angular-sampling-based methods have been extensively studied recently due to their ability to capture the continuous conformational space of protein structures. The literature has focused on using a variety of parametric models of the sequential dependencies between angle pairs along the protein chains. In this article, we present a thorough review of angular-sampling-based methods by assessing three main questions: What is the best distribution type to model the protein angles? What is a reasonable number of components in a mixture model that should be considered to accurately parameterize the joint distribution of the angles? and What is the order of the local sequence-structure dependency that should be considered by a prediction method? We assess the model fits for different methods using bivariate lag-distributions of the dihedral/planar angles. Moreover, the main information across the lags can be extracted using a technique called Lag singular value decomposition (LagSVD), which considers the joint distribution of the dihedral/planar angles over different lags using a nonparametric approach and monitors the behavior of the lag-distribution of the angles using singular value decomposition. As a result, we developed graphical tools and numerical measurements to compare and evaluate the performance of different model fits. Furthermore, we developed a web-tool (http://www.stat.tamu. edu/~madoliat/LagSVD) that can be used to produce informative animations. © The Author 2012. Published by Oxford University Press.

Solution Structure of a Novel C2-Symmetrical Bifunctional Bicyclic Inhibitor Based on SFTI-1

International Nuclear Information System (INIS)

Jaulent, Agnes M.; Brauer, Arnd B. E.; Matthews, Stephen J.; Leatherbarrow, Robin J.

2005-01-01

A novel bifunctional bicyclic inhibitor has been created that combines features both from the Bowman-Birk inhibitor (BBI) proteins, which have two distinct inhibitory sites, and from sunflower trypsin inhibitor-1 (SFTI-1), which has a compact bicyclic structure. The inhibitor was designed by fusing together a pair of reactive loops based on a sequence derived from SFTI-1 to create a backbone-cyclized disulfide-bridged 16-mer peptide. This peptide has two symmetrically spaced trypsin binding sites. Its synthesis and biological activity have been reported in a previous communication [Jaulent and Leatherbarrow, 2004, PEDS 17, 681]. In the present study we have examined the three-dimensional structure of the molecule. We find that the new inhibitor, which has a symmetrical 8-mer half-cystine CTKSIPP'I' motif repeated through a C 2 symmetry axis also shows a complete symmetry in its three-dimensional structure. Each of the two loops adopts the expected canonical conformation common to all BBIs as well as SFTI-1. We also find that the inhibitor displays a strong and unique structural identity, with a notable lack of minor conformational isomers that characterise most reactive site loop mimics examined to date as well as SFTI-1. This suggests that the presence of the additional cyclic loop acts to restrict conformational mobility and that the deliberate introduction of cyclic symmetry may offer a general route to locking the conformation of β-hairpin structures

Selecting Question-Specific Genes to Reduce Incongruence in Phylogenomics: A Case Study of Jawed Vertebrate Backbone Phylogeny.

Science.gov (United States)

Chen, Meng-Yun; Liang, Dan; Zhang, Peng

2015-11-01

Incongruence between different phylogenomic analyses is the main challenge faced by phylogeneticists in the genomic era. To reduce incongruence, phylogenomic studies normally adopt some data filtering approaches, such as reducing missing data or using slowly evolving genes, to improve the signal quality of data. Here, we assembled a phylogenomic data set of 58 jawed vertebrate taxa and 4682 genes to investigate the backbone phylogeny of jawed vertebrates under both concatenation and coalescent-based frameworks. To evaluate the efficiency of extracting phylogenetic signals among different data filtering methods, we chose six highly intractable internodes within the backbone phylogeny of jawed vertebrates as our test questions. We found that our phylogenomic data set exhibits substantial conflicting signal among genes for these questions. Our analyses showed that non-specific data sets that are generated without bias toward specific questions are not sufficient to produce consistent results when there are several difficult nodes within a phylogeny. Moreover, phylogenetic accuracy based on non-specific data is considerably influenced by the size of data and the choice of tree inference methods. To address such incongruences, we selected genes that resolve a given internode but not the entire phylogeny. Notably, not only can this strategy yield correct relationships for the question, but it also reduces inconsistency associated with data sizes and inference methods. Our study highlights the importance of gene selection in phylogenomic analyses, suggesting that simply using a large amount of data cannot guarantee correct results. Constructing question-specific data sets may be more powerful for resolving problematic nodes. © The Author(s) 2015. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PAF receptor structure: a hypothesis.

Science.gov (United States)

Godfroid, J J; Dive, G; Lamotte-Brasseur, J; Batt, J P; Heymans, F

1991-12-01

Different hypotheses of the structure of platelet-activating factor (PAF) receptor based on structure-activity relationships of agonists and antagonists are reviewed. For an agonistic effect, strong hydrophobic interactions and an ether function are required in position-1 of the glycerol backbone; chain length limitations and steric hindrance demand a small group in position-2. The unusual structural properties of non-PAF-like antagonists required 3-D electrostatic potential calculations. This method applied to seven potent antagonists suggests a strong "Cache-orielles" (ear-muff) effect, i.e., two strong electronegative wells (isocontour at -10 Kcal/mole) are located at 180 degrees to each other and at a relatively constant distance. Initial consideration of the "Cache-oreilles" effect implied the structure of a bipolarized cylinder of 10-12 A diameter for the receptor. However, very recent results on studies with agonists and antagonists structurally similar to PAF suggest that the receptor may in fact be a multi-polarized cylinder.

Structural basis for target protein recognition by the protein disulfide reductase thioredoxin

DEFF Research Database (Denmark)

Maeda, Kenji; Hägglund, Per; Finnie, Christine

2006-01-01

Thioredoxin is ubiquitous and regulates various target proteins through disulfide bond reduction. We report the structure of thioredoxin (HvTrxh2 from barley) in a reaction intermediate complex with a protein substrate, barley alpha-amylase/subtilisin inhibitor (BASI). The crystal structure...... of this mixed disulfide shows a conserved hydrophobic motif in thioredoxin interacting with a sequence of residues from BASI through van der Waals contacts and backbone-backbone hydrogen bonds. The observed structural complementarity suggests that the recognition of features around protein disulfides plays...... a major role in the specificity and protein disulfide reductase activity of thioredoxin. This novel insight into the function of thioredoxin constitutes a basis for comprehensive understanding of its biological role. Moreover, comparison with structurally related proteins shows that thioredoxin shares...

Backbone-hydrazone-containing biodegradable copolymeric micelles for anticancer drug delivery

Energy Technology Data Exchange (ETDEWEB)

Xu, Jing; Luan, Shujuan; Qin, Benkai; Wang, Yingying; Wang, Kai; Qi, Peilan; Song, Shiyong, E-mail: pharmsong@henu.edu.cn [Henan University, Institute of Pharmacy (China)

2016-11-15

Well-defined biodegradable, pH-sensitive amphiphilic block polymers, poly(ethylene glycol)-Hyd-poly(lactic acid) (mPEG-Hyd-PLA) which have acid-cleavable linkages in their backbones, were synthesized via ring-opening polymerization initiated from hydrazone-containing macroinitiators. Introducing a hydrazone bond onto the backbone of an amphiphilic copolymer will find a broad-spectrum encapsulation of hydrophobic drugs. Dynamic light scattering (DLS) and transmission electron microscopy showed that the diblock copolymers self-assembled into stable micelles with average diameters of 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles changed obviously in mildly acidic pH (multiple peaks from 1 to 202 nm appeared under a pH 4.0 condition) than in neutral, while there were no changes in the case of non-sensitive ones. Doxorubicin (DOX) and paclitaxel (PTX) were loaded with drug loading content ranging from 2.4 to 3.5 %, respectively. Interestingly, the anticancer drugs released from mPEG-Hyd-PLA micelles could also be promoted by the increased acidity. An in vitro cytotoxicity study showed that the DOX-loaded mPEG-Hyd-PLA micelles have significantly enhanced cytotoxicity against HepG2 cells compared with the non-sensitive poly(ethylene glycol)-block-poly(lactic acid) (mPEG-PLA) micelles. Confocal microscopy observation indicated that more DOX were delivered into the nuclei of cells following 6 or 12 h incubation with DOX-loaded mPEG-Hyd-PLA micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded mPEG-Hyd-PLA micelles over free DOX and DOX-loaded mPEG-PLA micelles. These hydrazone-containing pH-responsive degradable micelles provide a useful strategy for antitumor drug delivery.

Backbone-hydrazone-containing biodegradable copolymeric micelles for anticancer drug delivery

International Nuclear Information System (INIS)

Xu, Jing; Luan, Shujuan; Qin, Benkai; Wang, Yingying; Wang, Kai; Qi, Peilan; Song, Shiyong

2016-01-01

Well-defined biodegradable, pH-sensitive amphiphilic block polymers, poly(ethylene glycol)-Hyd-poly(lactic acid) (mPEG-Hyd-PLA) which have acid-cleavable linkages in their backbones, were synthesized via ring-opening polymerization initiated from hydrazone-containing macroinitiators. Introducing a hydrazone bond onto the backbone of an amphiphilic copolymer will find a broad-spectrum encapsulation of hydrophobic drugs. Dynamic light scattering (DLS) and transmission electron microscopy showed that the diblock copolymers self-assembled into stable micelles with average diameters of 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles changed obviously in mildly acidic pH (multiple peaks from 1 to 202 nm appeared under a pH 4.0 condition) than in neutral, while there were no changes in the case of non-sensitive ones. Doxorubicin (DOX) and paclitaxel (PTX) were loaded with drug loading content ranging from 2.4 to 3.5 %, respectively. Interestingly, the anticancer drugs released from mPEG-Hyd-PLA micelles could also be promoted by the increased acidity. An in vitro cytotoxicity study showed that the DOX-loaded mPEG-Hyd-PLA micelles have significantly enhanced cytotoxicity against HepG2 cells compared with the non-sensitive poly(ethylene glycol)-block-poly(lactic acid) (mPEG-PLA) micelles. Confocal microscopy observation indicated that more DOX were delivered into the nuclei of cells following 6 or 12 h incubation with DOX-loaded mPEG-Hyd-PLA micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded mPEG-Hyd-PLA micelles over free DOX and DOX-loaded mPEG-PLA micelles. These hydrazone-containing pH-responsive degradable micelles provide a useful strategy for antitumor drug delivery.

Structural aspects of catalytic mechanisms of endonucleases and their binding to nucleic acids

Energy Technology Data Exchange (ETDEWEB)

Zhukhlistova, N. E.; Balaev, V. V.; Lyashenko, A. V.; Lashkov, A. A., E-mail: alashkov83@gmail.com [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

2012-05-15

Endonucleases (EC 3.1) are enzymes of the hydrolase class that catalyze the hydrolytic cleavage of deoxyribonucleic and ribonucleic acids at any region of the polynucleotide chain. Endonucleases are widely used both in biotechnological processes and in veterinary medicine as antiviral agents. Medical applications of endonucleases in human cancer therapy hold promise. The results of X-ray diffraction studies of the spatial organization of endonucleases and their complexes and the mechanism of their action are analyzed and generalized. An analysis of the structural studies of this class of enzymes showed that the specific binding of enzymes to nucleic acids is characterized by interactions with nitrogen bases and the nucleotide backbone, whereas the nonspecific binding of enzymes is generally characterized by interactions only with the nucleic-acid backbone. It should be taken into account that the specificity can be modulated by metal ions and certain low-molecular-weight organic compounds. To test the hypotheses about specific and nonspecific nucleic-acid-binding proteins, it is necessary to perform additional studies of atomic-resolution three-dimensional structures of enzyme-nucleic-acid complexes by methods of structural biology.

Electrochemical synthesis of polyaniline in the presence of poly(amidosulfonic acid)s with different rigidity of polymer backbone and characterization of the films obtained

International Nuclear Information System (INIS)

Nekrasov, A.A.; Gribkova, O.L.; Eremina, T.V.; Isakova, A.A.; Ivanov, V.F.; Tverskoj, V.A.; Vannikov, A.V.

2008-01-01

We have studied electrochemical matrix polymerization of aniline in the presence of poly(amidosulfonic acid)s of different nature: poly(2-acrylamido-2-methyl-1-propanosulfonic acid) (PAMPSA, flexible backbone); poly(p,p'-(2,2'-disulfoacid)-diphenylene-iso-phthalamid) (i-PASA, semi-rigid backbone); poly(p,p'-(2,2'-disulfoacid)-diphelylene-tere-phthalamid) (t-PASA, rigid backbone). Also, we have investigated spectral and electrochemical properties of the films obtained, as well as their surface morphology. The matrix polymerization results in the formation of interpolymer complexes of polyaniline (PANI) and the above-cited polyacids. The acceleration of aniline electropolymerization in the presence of poly(amidosulfonic acid)s was observed due to association of aniline molecules to sulfonic groups of the polyacid and higher local concentration of protons near the polyacid backbone. The rigid-chain polyacids interfere with the normal course of the electropolymerization, which manifests itself in the changes of the shape of time dependences of absorbance and charge. Cyclic voltammetry and spectroelectrochemical experiments showed that the formation of interpolymer complex with rigid-chain polyacids distorts spectroelectrochemical characteristics of PANI. This evidently results from steric hindrances in the formation of quinoid units

X-Pol Potential: An Electronic Structure-Based Force Field for Molecular Dynamics Simulation of a Solvated Protein in Water.

Science.gov (United States)

Xie, Wangshen; Orozco, Modesto; Truhlar, Donald G; Gao, Jiali

2009-02-17

A recently proposed electronic structure-based force field called the explicit polarization (X-Pol) potential is used to study many-body electronic polarization effects in a protein, in particular by carrying out a molecular dynamics (MD) simulation of bovine pancreatic trypsin inhibitor (BPTI) in water with periodic boundary conditions. The primary unit cell is cubic with dimensions ~54 × 54 × 54 Å(3), and the total number of atoms in this cell is 14281. An approximate electronic wave function, consisting of 29026 basis functions for the entire system, is variationally optimized to give the minimum Born-Oppenheimer energy at every MD step; this allows the efficient evaluation of the required analytic forces for the dynamics. Intramolecular and intermolecular polarization and intramolecular charge transfer effects are examined and are found to be significant; for example, 17 out of 58 backbone carbonyls differ from neutrality on average by more than 0.1 electron, and the average charge on the six alanines varies from -0.05 to +0.09. The instantaneous excess charges vary even more widely; the backbone carbonyls have standard deviations in their fluctuating net charges from 0.03 to 0.05, and more than half of the residues have excess charges whose standard deviation exceeds 0.05. We conclude that the new-generation X-Pol force field permits the inclusion of time-dependent quantum mechanical polarization and charge transfer effects in much larger systems than was previously possible.

Adsorption of molecular brushes with polyelectrolyte backbones onto oppositely charged surfaces: A self-consistent field theory

NARCIS (Netherlands)

Feuz, L.; Leermakers, F.A.M.; Textor, M.; Borisov, O.V.

2008-01-01

The two-gradient version of the Scheutjens¿Fleer self-consistent field (SF-SCF) theory is employed to model the interaction between a molecular bottle brush with a polyelectrolyte backbone and neutral hydrophilic side chains and an oppositely charged surface. Our system mimics graft-copolymers with

Multi-source micro-friction identification for a class of cable-driven robots with passive backbone

Science.gov (United States)

Tjahjowidodo, Tegoeh; Zhu, Ke; Dailey, Wayne; Burdet, Etienne; Campolo, Domenico

2016-12-01

This paper analyses the dynamics of cable-driven robots with a passive backbone and develops techniques for their dynamic identification, which are tested on the H-Man, a planar cabled differential transmission robot for haptic interaction. The mechanism is optimized for human-robot interaction by accounting for the cost-benefit-ratio of the system, specifically by eliminating the necessity of an external force sensor to reduce the overall cost. As a consequence, this requires an effective dynamic model for accurate force feedback applications which include friction behavior in the system. We first consider the significance of friction in both the actuator and backbone spaces. Subsequently, we study the required complexity of the stiction model for the application. Different models representing different levels of complexity are investigated, ranging from the conventional approach of Coulomb to an advanced model which includes hysteresis. The results demonstrate each model's ability to capture the dynamic behavior of the system. In general, it is concluded that there is a trade-off between model accuracy and the model cost.

Structural determinants of phenotypic diversity and replication rate of human prions.

Directory of Open Access Journals (Sweden)

Jiri G Safar

2015-04-01

Full Text Available The infectious pathogen responsible for prion diseases is the misfolded, aggregated form of the prion protein, PrPSc. In contrast to recent progress in studies of laboratory rodent-adapted prions, current understanding of the molecular basis of human prion diseases and, especially, their vast phenotypic diversity is very limited. Here, we have purified proteinase resistant PrPSc aggregates from two major phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD, determined their conformational stability and replication tempo in vitro, as well as characterized structural organization using recently emerged approaches based on hydrogen/deuterium (H/D exchange coupled with mass spectrometry. Our data clearly demonstrate that these phenotypically distant prions differ in a major way with regard to their structural organization, both at the level of the polypeptide backbone (as indicated by backbone amide H/D exchange data as well as the quaternary packing arrangements (as indicated by H/D exchange kinetics for histidine side chains. Furthermore, these data indicate that, in contrast to previous observations on yeast and some murine prion strains, the replication rate of sCJD prions is primarily determined not by conformational stability but by specific structural features that control the growth rate of prion protein aggregates.

Conservation and Divergence in the Candida Species Biofilm Matrix Mannan-Glucan Complex Structure, Function, and Genetic Control.

Science.gov (United States)

Dominguez, Eddie; Zarnowski, Robert; Sanchez, Hiram; Covelli, Antonio S; Westler, William M; Azadi, Parastoo; Nett, Jeniel; Mitchell, Aaron P; Andes, David R

2018-04-03

Candida biofilms resist the effects of available antifungal therapies. Prior studies with Candida albicans biofilms show that an extracellular matrix mannan-glucan complex (MGCx) contributes to antifungal sequestration, leading to drug resistance. Here we implement biochemical, pharmacological, and genetic approaches to explore a similar mechanism of resistance for the three most common clinically encountered non- albicans Candida species (NAC). Our findings reveal that each Candida species biofilm synthesizes a mannan-glucan complex and that the antifungal-protective function of this complex is conserved. Structural similarities extended primarily to the polysaccharide backbone (α-1,6-mannan and β-1,6-glucan). Surprisingly, biochemical analysis uncovered stark differences in the branching side chains of the MGCx among the species. Consistent with the structural analysis, similarities in the genetic control of MGCx production for each Candida species also appeared limited to the synthesis of the polysaccharide backbone. Each species appears to employ a unique subset of modification enzymes for MGCx synthesis, likely accounting for the observed side chain diversity. Our results argue for the conservation of matrix function among Candida spp. While biogenesis is preserved at the level of the mannan-glucan complex backbone, divergence emerges for construction of branching side chains. Thus, the MGCx backbone represents an ideal drug target for effective pan- Candida species biofilm therapy. IMPORTANCE Candida species, the most common fungal pathogens, frequently grow as a biofilm. These adherent communities tolerate extremely high concentrations of antifungal agents, due in large part, to a protective extracellular matrix. The present studies define the structural, functional, and genetic similarities and differences in the biofilm matrix from the four most common Candida species. Each species synthesizes an extracellular mannan-glucan complex (MGCx) which

Side chain effect on electronic structure of spin-coated films of [6,6]-phenyl-C61-butyric acid methyl ester and its bis-adduct

International Nuclear Information System (INIS)

Akaike, Kouki; Kanai, Kaname; Ouchi, Yukio; Seki, Kazuhiko

2013-01-01

Highlights: ► Electronic structure of spin-coated films of PCBM and bis-PCBM was investigated. ► Ionization energy and electron affinity of bis-PCBM are smaller than those of PCBM. ► Electron donation from the side chain to C 60 -backbone raises the HOMO and LUMO. ► Open circuit voltages of PCBM-based solar cells relates to electron affinities. - Abstract: We investigated the electronic structure of spin-coated films of two soluble fullerenes; [6,6]-phenyl-C 61 -butyric acid methyl ester (PCBM) and its bis-adduct (bis-PCBM) using ultraviolet photoelectron spectroscopy, inverse photoemission spectroscopy and molecular orbital calculations. The ionization energy and electron affinity of spin-coated films of bis-PCBM were determined to be 6.01 eV and 3.4 eV, respectively. Analysis of electron density suggested the stronger electron donation from the two side chains to fullerene-backbone in a bis-PCBM molecule, compared with PCBM. The electron donation raises the energies of the frontier orbitals of bis-PCBM, which mainly consist of π-orbitals of fullerene-backbone. As a result, the ionization energy and electron affinity of bis-PCBM are smaller than those of PCBM. Moreover, we also concluded that the larger open circuit voltage observed for bis-PCBM based organic photovoltaics was explained by the higher-lying unoccupied molecular orbital of bis-PCBM

Reduced dimensionality (3,2)D NMR experiments and their automated analysis: implications to high-throughput structural studies on proteins.

Science.gov (United States)

Reddy, Jithender G; Kumar, Dinesh; Hosur, Ramakrishna V

2015-02-01

Protein NMR spectroscopy has expanded dramatically over the last decade into a powerful tool for the study of their structure, dynamics, and interactions. The primary requirement for all such investigations is sequence-specific resonance assignment. The demand now is to obtain this information as rapidly as possible and in all types of protein systems, stable/unstable, soluble/insoluble, small/big, structured/unstructured, and so on. In this context, we introduce here two reduced dimensionality experiments – (3,2)D-hNCOcanH and (3,2)D-hNcoCAnH – which enhance the previously described 2D NMR-based assignment methods quite significantly. Both the experiments can be recorded in just about 2-3 h each and hence would be of immense value for high-throughput structural proteomics and drug discovery research. The applicability of the method has been demonstrated using alpha-helical bovine apo calbindin-D9k P43M mutant (75 aa) protein. Automated assignment of this data using AUTOBA has been presented, which enhances the utility of these experiments. The backbone resonance assignments so derived are utilized to estimate secondary structures and the backbone fold using Web-based algorithms. Taken together, we believe that the method and the protocol proposed here can be used for routine high-throughput structural studies of proteins. Copyright © 2014 John Wiley & Sons, Ltd.

Backbone dynamics of a biologically active human FGF-1 monomer, complexed to a hexasaccharide heparin-analogue, by 15N NMR relaxation methods

International Nuclear Information System (INIS)

Canales-Mayordomo, Angeles; Fayos, Rosa; Angulo, Jesus; Ojeda, Rafael; Martin-Pastor, Manuel; Nieto, Pedro M.; Martin-Lomas, Manuel; Lozano, Rosa; Gimenez-Gallego, Guillermo; Jimenez-Barbero, Jesus

2006-01-01

The binding site and backbone dynamics of a bioactive complex formed by the acidic fibroblast growth factor (FGF-1) and a specifically designed heparin hexasaccharide has been investigated by HSQC and relaxation NMR methods. The comparison of the relaxation data for the free and bound states has allowed showing that the complex is monomeric, and still induces mutagenesis, and that the protein backbone presents reduced motion in different timescale in its bound state, except in certain points that are involved in the interaction with the fibroblast growth factor receptor (FGFR)

Conformation-independent structural comparison of macromolecules with ProSMART

International Nuclear Information System (INIS)

Nicholls, Robert A.; Fischer, Marcus; McNicholas, Stuart; Murshudov, Garib N.

2014-01-01

The Procrustes Structural Matching Alignment and Restraints Tool (ProSMART) has been developed to allow local comparative structural analyses independent of the global conformations and sequence homology of the compared macromolecules. This allows quick and intuitive visualization of the conservation of backbone and side-chain conformations, providing complementary information to existing methods. The identification and exploration of (dis)similarities between macromolecular structures can help to gain biological insight, for instance when visualizing or quantifying the response of a protein to ligand binding. Obtaining a residue alignment between compared structures is often a prerequisite for such comparative analysis. If the conformational change of the protein is dramatic, conventional alignment methods may struggle to provide an intuitive solution for straightforward analysis. To make such analyses more accessible, the Procrustes Structural Matching Alignment and Restraints Tool (ProSMART) has been developed, which achieves a conformation-independent structural alignment, as well as providing such additional functionalities as the generation of restraints for use in the refinement of macromolecular models. Sensible comparison of protein (or DNA/RNA) structures in the presence of conformational changes is achieved by enforcing neither chain nor domain rigidity. The visualization of results is facilitated by popular molecular-graphics software such as CCP4mg and PyMOL, providing intuitive feedback regarding structural conservation and subtle dissimilarities between close homologues that can otherwise be hard to identify. Automatically generated colour schemes corresponding to various residue-based scores are provided, which allow the assessment of the conservation of backbone and side-chain conformations relative to the local coordinate frame. Structural comparison tools such as ProSMART can help to break the complexity that accompanies the constantly growing

Conformation-independent structural comparison of macromolecules with ProSMART

Energy Technology Data Exchange (ETDEWEB)

Nicholls, Robert A., E-mail: nicholls@mrc-lmb.cam.ac.uk [MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH (United Kingdom); Fischer, Marcus [University of California San Francisco, San Francisco, CA 94158 (United States); McNicholas, Stuart [University of York, Heslington, York YO10 5DD (United Kingdom); Murshudov, Garib N. [MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH (United Kingdom)

2014-09-01

The Procrustes Structural Matching Alignment and Restraints Tool (ProSMART) has been developed to allow local comparative structural analyses independent of the global conformations and sequence homology of the compared macromolecules. This allows quick and intuitive visualization of the conservation of backbone and side-chain conformations, providing complementary information to existing methods. The identification and exploration of (dis)similarities between macromolecular structures can help to gain biological insight, for instance when visualizing or quantifying the response of a protein to ligand binding. Obtaining a residue alignment between compared structures is often a prerequisite for such comparative analysis. If the conformational change of the protein is dramatic, conventional alignment methods may struggle to provide an intuitive solution for straightforward analysis. To make such analyses more accessible, the Procrustes Structural Matching Alignment and Restraints Tool (ProSMART) has been developed, which achieves a conformation-independent structural alignment, as well as providing such additional functionalities as the generation of restraints for use in the refinement of macromolecular models. Sensible comparison of protein (or DNA/RNA) structures in the presence of conformational changes is achieved by enforcing neither chain nor domain rigidity. The visualization of results is facilitated by popular molecular-graphics software such as CCP4mg and PyMOL, providing intuitive feedback regarding structural conservation and subtle dissimilarities between close homologues that can otherwise be hard to identify. Automatically generated colour schemes corresponding to various residue-based scores are provided, which allow the assessment of the conservation of backbone and side-chain conformations relative to the local coordinate frame. Structural comparison tools such as ProSMART can help to break the complexity that accompanies the constantly growing

Side chain effect on electronic structure of spin-coated films of [6,6]-phenyl-C{sub 61}-butyric acid methyl ester and its bis-adduct

Energy Technology Data Exchange (ETDEWEB)

Akaike, Kouki, E-mail: akaike@riken.jp [Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602 (Japan); Kanai, Kaname [Department of Physics, Faculty of Science and Technology, Tokyo University of Science, Yamazaki 2641, Noda 278-8510 (Japan); Ouchi, Yukio; Seki, Kazuhiko [Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602 (Japan)

2013-03-29

Highlights: ► Electronic structure of spin-coated films of PCBM and bis-PCBM was investigated. ► Ionization energy and electron affinity of bis-PCBM are smaller than those of PCBM. ► Electron donation from the side chain to C{sub 60}-backbone raises the HOMO and LUMO. ► Open circuit voltages of PCBM-based solar cells relates to electron affinities. - Abstract: We investigated the electronic structure of spin-coated films of two soluble fullerenes; [6,6]-phenyl-C{sub 61}-butyric acid methyl ester (PCBM) and its bis-adduct (bis-PCBM) using ultraviolet photoelectron spectroscopy, inverse photoemission spectroscopy and molecular orbital calculations. The ionization energy and electron affinity of spin-coated films of bis-PCBM were determined to be 6.01 eV and 3.4 eV, respectively. Analysis of electron density suggested the stronger electron donation from the two side chains to fullerene-backbone in a bis-PCBM molecule, compared with PCBM. The electron donation raises the energies of the frontier orbitals of bis-PCBM, which mainly consist of π-orbitals of fullerene-backbone. As a result, the ionization energy and electron affinity of bis-PCBM are smaller than those of PCBM. Moreover, we also concluded that the larger open circuit voltage observed for bis-PCBM based organic photovoltaics was explained by the higher-lying unoccupied molecular orbital of bis-PCBM.

LoopX: A Graphical User Interface-Based Database for Comprehensive Analysis and Comparative Evaluation of Loops from Protein Structures.

Science.gov (United States)

Kadumuri, Rajashekar Varma; Vadrevu, Ramakrishna

2017-10-01

Due to their crucial role in function, folding, and stability, protein loops are being targeted for grafting/designing to create novel or alter existing functionality and improve stability and foldability. With a view to facilitate a thorough analysis and effectual search options for extracting and comparing loops for sequence and structural compatibility, we developed, LoopX a comprehensively compiled library of sequence and conformational features of ∼700,000 loops from protein structures. The database equipped with a graphical user interface is empowered with diverse query tools and search algorithms, with various rendering options to visualize the sequence- and structural-level information along with hydrogen bonding patterns, backbone φ, ψ dihedral angles of both the target and candidate loops. Two new features (i) conservation of the polar/nonpolar environment and (ii) conservation of sequence and conformation of specific residues within the loops have also been incorporated in the search and retrieval of compatible loops for a chosen target loop. Thus, the LoopX server not only serves as a database and visualization tool for sequence and structural analysis of protein loops but also aids in extracting and comparing candidate loops for a given target loop based on user-defined search options.

Insight into a conformation of the PNA-PNA duplex with (2‧R,4‧R)- and (2‧R,4‧S)-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbones

Science.gov (United States)

Maitarad, Amphawan; Poomsuk, Nattawee; Vilaivan, Chotima; Vilaivan, Tirayut; Siriwong, Khatcharin

2018-04-01

Suitable conformations for peptide nucleic acid (PNA) self-hybrids with (2‧R,4‧R)- and (2‧R,4‧S)-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbones (namely, acpcPNA and epi-acpcPNA, respectively) were investigated based on molecular dynamics simulations. The results revealed that hybridization of the acpcPNA was observed only in the parallel direction, with a conformation close to the P-type structure. In contrast, self-hybrids of the epi-acpcPNA were formed in the antiparallel and parallel directions; the antiparallel duplex adopted the B-form conformation, and the parallel duplex was between B- and P-forms. The calculated binding energies and the experimental data indicate that the antiparallel epi-acpcPNA self-hybrid was more stable than the parallel duplex.

Five and four dimensional experiments for robust backbone resonance assignment of large intrinsically disordered proteins: application to Tau3x protein

International Nuclear Information System (INIS)

Żerko, Szymon; Byrski, Piotr; Włodarczyk-Pruszyński, Paweł; Górka, Michał; Ledolter, Karin; Masliah, Eliezer; Konrat, Robert; Koźmiński, Wiktor

2016-01-01

New experiments dedicated for large IDPs backbone resonance assignment are presented. The most distinctive feature of all described techniques is the employment of MOCCA-XY16 mixing sequences to obtain effective magnetization transfers between carbonyl carbon backbone nuclei. The proposed 4 and 5 dimensional experiments provide a high dispersion of obtained signals making them suitable for use in the case of large IDPs (application to 354 a. a. residues of Tau protein 3x isoform is presented) as well as provide both forward and backward connectivities. What is more, connecting short chains interrupted with proline residues is also possible. All the experiments employ non-uniform sampling.

Five and four dimensional experiments for robust backbone resonance assignment of large intrinsically disordered proteins: application to Tau3x protein

Energy Technology Data Exchange (ETDEWEB)

Żerko, Szymon; Byrski, Piotr; Włodarczyk-Pruszyński, Paweł; Górka, Michał [University of Warsaw, Faculty of Chemistry, Biological and Chemical Research Centre (Poland); Ledolter, Karin [University of Vienna, Department of Computational and Structural Biology, Max F. Perutz Laboratories (Austria); Masliah, Eliezer [University of California, San Diego, Departments of Neuroscience and Pathology (United States); Konrat, Robert [University of Vienna, Department of Computational and Structural Biology, Max F. Perutz Laboratories (Austria); Koźmiński, Wiktor, E-mail: kozmin@chem.uw.edu.pl [University of Warsaw, Faculty of Chemistry, Biological and Chemical Research Centre (Poland)

2016-08-15

New experiments dedicated for large IDPs backbone resonance assignment are presented. The most distinctive feature of all described techniques is the employment of MOCCA-XY16 mixing sequences to obtain effective magnetization transfers between carbonyl carbon backbone nuclei. The proposed 4 and 5 dimensional experiments provide a high dispersion of obtained signals making them suitable for use in the case of large IDPs (application to 354 a. a. residues of Tau protein 3x isoform is presented) as well as provide both forward and backward connectivities. What is more, connecting short chains interrupted with proline residues is also possible. All the experiments employ non-uniform sampling.

Solution structure of apamin determined by nuclear magnetic resonance and distance geometry

Energy Technology Data Exchange (ETDEWEB)

Pease, J.H.B.; Wemmer, D.E.

1988-11-01

The solution structure of the bee venom neurotoxin apamin has been determined with a distance geometry program using distance constraints derived from NMR. Twenty embedded structures were generated and refined by using the program DSPACE. After error minimization using both conjugate gradient and dynamics algorithms, six structures had very low residual error. Comparisons of these show that the backbone of the peptide is quite well-defined with the largest rms difference between backbone atoms in these structures of 1.34 /Angstrom/. The side chains have far fewer constraints and show greater variability in their positions. The structure derived here is generally consistent with the qualitative model previously described, with most differences occurring in the loop between the ..beta..-turn (residues 2-5) and the C-terminal ..cap alpha..-helix (residues 9-17). Comparisons are made with previously derived models from NMR data and other methods.

Solution structure of apamin determined by nuclear magnetic resonance and distance geometry

International Nuclear Information System (INIS)

Pease, J.H.B.; Wemmer, D.E.

1988-01-01

The solution structure of the bee venom neurotoxin apamin has been determined with a distance geometry program using distance constraints derived from NMR. Twenty embedded structures were generated and refined by using the program DSPACE. After error minimization using both conjugate gradient and dynamics algorithms, six structures had very low residual error. Comparisons of these show that the backbone of the peptide is quite well-defined with the largest rms difference between backbone atoms in these structures of 1.34 /Angstrom/. The side chains have far fewer constraints and show greater variability in their positions. The structure derived here is generally consistent with the qualitative model previously described, with most differences occurring in the loop between the β-turn (residues 2-5) and the C-terminal α-helix (residues 9-17). Comparisons are made with previously derived models from NMR data and other methods

Spectral fitting for signal assignment and structural analysis of uniformly {sup 13}C-labeled solid proteins by simulated annealing based on chemical shifts and spin dynamics

Energy Technology Data Exchange (ETDEWEB)

Matsuki, Yoh; Akutsu, Hideo; Fujiwara, Toshimichi [Osaka University, Institute for Protein Research (Japan)], E-mail: tfjwr@protein.osaka-u.ac.jp

2007-08-15

We describe an approach for the signal assignment and structural analysis with a suite of two-dimensional {sup 13}C-{sup 13}C magic-angle-spinning solid-state NMR spectra of uniformly {sup 13}C-labeled peptides and proteins. We directly fit the calculated spectra to experimental ones by simulated annealing in restrained molecular dynamics program CNS as a function of atomic coordinates. The spectra are calculated from the conformation dependent chemical shift obtained with SHIFTX and the cross-peak intensities computed for recoupled dipolar interactions. This method was applied to a membrane-bound 14-residue peptide, mastoparan-X. The obtained C', C{sup {alpha}} and C{sup {beta}} chemical shifts agreed with those reported previously at the precisions of 0.2, 0.7 and 0.4 ppm, respectively. This spectral fitting program also provides backbone dihedral angles with a precision of about 50 deg. from the spectra even with resonance overlaps. The restraints on the angles were improved by applying protein database program TALOS to the obtained chemical shifts. The peptide structure provided by these restraints was consistent with the reported structure at the backbone RMSD of about 1 A.

Contribution of peptide backbone to Anti-citrulline-dependent antibody reactivity

DEFF Research Database (Denmark)

Trier, Nicole Hartwig; Dam, Catharina; Olsen, Dorthe

2015-01-01

for ACPA reactivity and to be cross-reactive between the selected citrullinated peptides. The remaining amino acids within the citrullinated peptides were found to be of less importance for antibody reactivity. Moreover, these findings indicated that the Cit-Gly motif in combination with peptide backbone...... found in up to 70% of RA patients’ sera, have received much attention. Several citrullinated proteins are associated with RA, suggesting that ACPAs may react with different sequence patterns, separating them from traditional antibodies, whose reactivity usually is specific towards a single target...... homology rather than sequence homology are favored between citrullinated epitopes. These findings are important in relation to clarifying the etiology of RA and to determine the nature of ACPAs, e.g. why some Cit-Gly-containing sequences are not targeted by ACPAs....

Backbone dynamics of a biologically active human FGF-1 monomer, complexed to a hexasaccharide heparin-analogue, by {sup 15}N NMR relaxation methods

Energy Technology Data Exchange (ETDEWEB)

Canales-Mayordomo, Angeles; Fayos, Rosa [Centro de Investigaciones Biologicas, CSIC, Departamento de Estructura y Funcion de Proteinas (Spain); Angulo, Jesus; Ojeda, Rafael [Instituto de Investigaciones Quimicas, CSIC, Grupo de Carbohidratos (Spain); Martin-Pastor, Manuel [Unidad de RM y Unidad de RMN de Biomoleculas Asociada al CSIC, Laboratorio de Estructura e Estructura de Biomoleculas Jose Carracido (Spain); Nieto, Pedro M.; Martin-Lomas, Manuel [Instituto de Investigaciones Quimicas, CSIC, Grupo de Carbohidratos (Spain); Lozano, Rosa; Gimenez-Gallego, Guillermo; Jimenez-Barbero, Jesus [Centro de Investigaciones Biologicas, CSIC, Departamento de Estructura y Funcion de Proteinas (Spain)], E-mail: jjbarbero@cib.csic.es

2006-08-15

The binding site and backbone dynamics of a bioactive complex formed by the acidic fibroblast growth factor (FGF-1) and a specifically designed heparin hexasaccharide has been investigated by HSQC and relaxation NMR methods. The comparison of the relaxation data for the free and bound states has allowed showing that the complex is monomeric, and still induces mutagenesis, and that the protein backbone presents reduced motion in different timescale in its bound state, except in certain points that are involved in the interaction with the fibroblast growth factor receptor (FGFR)

On the purported "backbone fluorescence" in protein three-dimensional fluorescence spectra

DEFF Research Database (Denmark)

Bortolotti, Annalisa; Wong, Yin How; Korsholm, Stine S.

2016-01-01

In this study, several proteins (albumin, lysozyme, insulin) and model compounds (Trp, Tyr, homopolypeptides) were used to demonstrate the origin of the fluorescence observed upon their excitation at 220-230 nm. In the last 10 years we have observed a worrying increase in the number of articles...... as any traditional protein emission spectrum. The many papers in reputable journals erroneously reporting this peak assignment, contradicting 5 decades of prior knowledge, have led to the creation of a new dogma, where many authors and reviewers now take the purported backbone fluorescence...... as an established fact. We hope the current paper helps counter this new situation and leads to a reassessment of those papers that make this erroneous claim....

Dioxaphosphorinane-constrained nucleic Acid dinucleotides as tools for structural tuning of nucleic acids.

Science.gov (United States)

Catana, Dan-Andrei; Renard, Brice-Loïc; Maturano, Marie; Payrastre, Corinne; Tarrat, Nathalie; Escudier, Jean-Marc

2012-01-01

We describe a rational approach devoted to modulate the sugar-phosphate backbone geometry of nucleic acids. Constraints were generated by connecting one oxygen of the phosphate group to a carbon of the sugar moiety. The so-called dioxaphosphorinane rings were introduced at key positions along the sugar-phosphate backbone allowing the control of the six-torsion angles α to ζ defining the polymer structure. The syntheses of all the members of the D-CNA family are described, and we emphasize the effect on secondary structure stabilization of a couple of diastereoisomers of α,β-D-CNA exhibiting wether B-type canonical values or not.

Dioxaphosphorinane-Constrained Nucleic Acid Dinucleotides as Tools for Structural Tuning of Nucleic Acids

Directory of Open Access Journals (Sweden)

Dan-Andrei Catana

2012-01-01

Full Text Available We describe a rational approach devoted to modulate the sugar-phosphate backbone geometry of nucleic acids. Constraints were generated by connecting one oxygen of the phosphate group to a carbon of the sugar moiety. The so-called dioxaphosphorinane rings were introduced at key positions along the sugar-phosphate backbone allowing the control of the six-torsion angles α to ζ defining the polymer structure. The syntheses of all the members of the D-CNA family are described, and we emphasize the effect on secondary structure stabilization of a couple of diastereoisomers of α,β-D-CNA exhibiting wether B-type canonical values or not.

Determination of Backbone Amide Hydrogen Exchange Rates of Cytochrome c Using Partially Scrambled Electron Transfer Dissociation Data

Science.gov (United States)

Hamuro, Yoshitomo; E, Sook Yen

2018-05-01

The technological goal of hydrogen/deuterium exchange-mass spectrometry (HDX-MS) is to determine backbone amide hydrogen exchange rates. The most critical challenge to achieve this goal is obtaining the deuterium incorporation in single-amide resolution, and gas-phase fragmentation may provide a universal solution. The gas-phase fragmentation may generate the daughter ions which differ by a single amino acid and the difference in deuterium incorporations in the two analogous ions can yield the deuterium incorporation at the sub-localized site. Following the pioneering works by Jørgensen and Rand, several papers utilized the electron transfer dissociation (ETD) to determine the location of deuterium in single-amide resolution. This paper demonstrates further advancement of the strategy by determining backbone amide hydrogen exchange rates, instead of just determining deuterium incorporation at a single time point, in combination with a wide time window monitoring. A method to evaluate the effects of scrambling and to determine the exchange rates from partially scrambled HDX-ETD-MS data is described. All parent ions for ETD fragmentation were regio-selectively scrambled: The deuterium in some regions of a peptide ion was scrambled while that in the other regions was not scrambled. The method determined 31 backbone amide hydrogen exchange rates of cytochrome c in the non-scrambled regions. Good fragmentation of a parent ion, a low degree of scrambling, and a low number of exchangeable hydrogens in the preceding side chain are the important factors to determine the exchange rate. The exchange rates determined by the HDX-MS are in good agreement with those determined by NMR. [Figure not available: see fulltext.

Determination of Backbone Amide Hydrogen Exchange Rates of Cytochrome c Using Partially Scrambled Electron Transfer Dissociation Data.

Science.gov (United States)

Hamuro, Yoshitomo; E, Sook Yen

2018-05-01

The technological goal of hydrogen/deuterium exchange-mass spectrometry (HDX-MS) is to determine backbone amide hydrogen exchange rates. The most critical challenge to achieve this goal is obtaining the deuterium incorporation in single-amide resolution, and gas-phase fragmentation may provide a universal solution. The gas-phase fragmentation may generate the daughter ions which differ by a single amino acid and the difference in deuterium incorporations in the two analogous ions can yield the deuterium incorporation at the sub-localized site. Following the pioneering works by Jørgensen and Rand, several papers utilized the electron transfer dissociation (ETD) to determine the location of deuterium in single-amide resolution. This paper demonstrates further advancement of the strategy by determining backbone amide hydrogen exchange rates, instead of just determining deuterium incorporation at a single time point, in combination with a wide time window monitoring. A method to evaluate the effects of scrambling and to determine the exchange rates from partially scrambled HDX-ETD-MS data is described. All parent ions for ETD fragmentation were regio-selectively scrambled: The deuterium in some regions of a peptide ion was scrambled while that in the other regions was not scrambled. The method determined 31 backbone amide hydrogen exchange rates of cytochrome c in the non-scrambled regions. Good fragmentation of a parent ion, a low degree of scrambling, and a low number of exchangeable hydrogens in the preceding side chain are the important factors to determine the exchange rate. The exchange rates determined by the HDX-MS are in good agreement with those determined by NMR. Graphical Abstract ᅟ.

Determination of Backbone Amide Hydrogen Exchange Rates of Cytochrome c Using Partially Scrambled Electron Transfer Dissociation Data

Science.gov (United States)

Hamuro, Yoshitomo; E, Sook Yen

2018-03-01

The technological goal of hydrogen/deuterium exchange-mass spectrometry (HDX-MS) is to determine backbone amide hydrogen exchange rates. The most critical challenge to achieve this goal is obtaining the deuterium incorporation in single-amide resolution, and gas-phase fragmentation may provide a universal solution. The gas-phase fragmentation may generate the daughter ions which differ by a single amino acid and the difference in deuterium incorporations in the two analogous ions can yield the deuterium incorporation at the sub-localized site. Following the pioneering works by Jørgensen and Rand, several papers utilized the electron transfer dissociation (ETD) to determine the location of deuterium in single-amide resolution. This paper demonstrates further advancement of the strategy by determining backbone amide hydrogen exchange rates, instead of just determining deuterium incorporation at a single time point, in combination with a wide time window monitoring. A method to evaluate the effects of scrambling and to determine the exchange rates from partially scrambled HDX-ETD-MS data is described. All parent ions for ETD fragmentation were regio-selectively scrambled: The deuterium in some regions of a peptide ion was scrambled while that in the other regions was not scrambled. The method determined 31 backbone amide hydrogen exchange rates of cytochrome c in the non-scrambled regions. Good fragmentation of a parent ion, a low degree of scrambling, and a low number of exchangeable hydrogens in the preceding side chain are the important factors to determine the exchange rate. The exchange rates determined by the HDX-MS are in good agreement with those determined by NMR. [Figure not available: see fulltext.

Noncanonical alpha/gamma Backbone Conformations in RNA and the Accuracy of Their Description by the AMBER Force Field

Czech Academy of Sciences Publication Activity Database

Zgarbová, M.; Jurečka, P.; Banáš, P.; Havrila, Marek; Šponer, Jiří; Otyepka, M.

2017-01-01

Roč. 121, č. 11 (2017), s. 2420-2433 ISSN 1520-6106 Institutional support: RVO:68081707 Keywords : molecular-dynamics simulations * sugar-phosphate backbone * free-energy landscape * ribosomal-rna Subject RIV: BO - Biophysics OBOR OECD: Physical chemistry Impact factor: 3.177, year: 2016

Facile access to unnatural dipeptide-alcohols based on cis-2,5-disubstituted pyrrolidines.

Science.gov (United States)

Jia, Yan-Yan; Li, Xiao-Ye; Wang, Ping-An; Wen, Ai-Dong

2015-02-11

Well-defined unnatural dipeptide-alcohols based on a cis-2,5-disubstitued pyrrolidine backbone were synthesized from commercially available starting materials meso-diethyl-2,5-dibromoadipate, (S)-(-)-1-phenylethylamine, and phenylalaninol. The structures of these unnatural dipeptide-alcohols are supported by HRMS, 1H- and 13C-NMR spectroscopy. These unnatural dipeptide-alcohols can act as building blocks for peptidomimetics.

Effect of short-chain branching on interfacial polymer structure and dynamics under shear flow.

Science.gov (United States)

Jeong, Sohdam; Kim, Jun Mo; Cho, Soowon; Baig, Chunggi

2017-11-22

We present a detailed analysis on the effect of short-chain branches on the structure and dynamics of interfacial chains using atomistic nonequilibrium molecular dynamics simulations of confined polyethylene melts in a wide range of shear rates. The intrinsically fast random motions of the short branches constantly disturb the overall chain conformation, leading to a more compact and less deformed chain structure of the short-chain branched (SCB) polymer against the imposed flow field in comparison with the corresponding linear polymer. Moreover, such highly mobile short branches along the backbone of the SCB polymer lead to relatively weaker out-of-plane wagging dynamics of interfacial chains, with highly curvy backbone structures in the intermediate flow regime. In conjunction with the contribution of short branches (as opposed to that of the backbone) to the total interfacial friction between the chains and the wall, the SCB polymer shows a nearly constant behavior in the degree of slip (d s ) with respect to shear rate in the weak-to-intermediate flow regimes. On the contrary, in the strong flow regime where irregular chain rotation and tumbling dynamics occur via intensive dynamical collisions between interfacial chains and the wall, an enhancement effect on the chain detachment from the wall, caused by short branches, leads to a steeper increase in d s for the SCB polymer than for the linear polymer. Remarkably, the SCB chains at the interface exhibit two distinct types of rolling mechanisms along the backbone, with a half-dumbbell mesoscopic structure at strong flow fields, in addition to the typical hairpin-like tumbling behavior displayed by the linear chains.

Structural similarities between prokaryotic and eukaryotic 5S ribosomal RNAs

International Nuclear Information System (INIS)

Welfle, H.; Boehm, S.; Damaschun, G.; Fabian, H.; Gast, K.; Misselwitz, R.; Mueller, J.J.; Zirwer, D.; Filimonov, V.V.; Venyaminov, S.Yu.; Zalkova, T.N.

1986-01-01

5S RNAs from rat liver and E. coli have been studied by diffuse X-ray and dynamic light scattering and by infrared and Raman spectroscopy. Identical structures at a resolution of 1 nm can be deduced from the comparison of the experimental X-ray scattering curves and electron distance distribution functions and from the agreement of the shape parameters. A flat shape model with a compact central region and two protruding arms was derived. Double helical stems are eleven-fold helices with a mean base pair distance of 0.28 nm. The number of base pairs (26 GC, 9 AU for E. coli; 27 GC, 9 AU for rat liver) and the degree of base stacking are the same within the experimental error. A very high regularity in the ribophosphate backbone is indicated for both 5S RNAs. The observed structural similarity and the consensus secondary structure pattern derived from comparative sequence analyses suggest the conclusion that prokaryotic and eukaryotic 5S RNAs are in general very similar with respect to their fundamental structural features. (author)

A new strategy for backbone resonance assignment in large proteins using a MQ-HACACO experiment

International Nuclear Information System (INIS)

Pervushin, Konstantin; Eletsky, Alexander

2003-01-01

A new strategy of backbone resonance assignment is proposed based on a combination of the most sensitive TROSY-type triple resonance experiments such as TROSY-HNCA and TROSY-HNCO with a new 3D multiple-quantum HACACO experiment. The favourable relaxation properties of the multiple-quantum coherences and signal detection using the 13 C' antiphase coherences optimize the performance of the proposed experiment for application to larger proteins. In addition to the 1 H N , 15 N, 13 C α and 13 C' chemical shifts the 3D multiple-quantum HACACO experiment provides assignment for the 1 H α resonances in contrast to previously proposed experiments for large proteins. The strategy is demonstrated with the 44 kDa uniformly 15 N, 13 C-labeled and fractionally 35% deuterated trimeric B. subtilis Chorismate Mutase measured at 20 deg. C and 9 deg. C. Measurements at the lower temperature indicate that the new strategy can be applied to even larger proteins with molecular weights up to 80 kDa

Mapping the backbone of science.

Energy Technology Data Exchange (ETDEWEB)

Klavans, Richard (Indiana University, Bloomington, IN); BÞorner, Katy (Strategies for Science & Technology, Incorporation, Berwyn, PA); Boyack, Kevin W.

2004-11-01

This paper presents a new map representing the structure of all of science, based on journal articles, including both the natural and social sciences. Similar to cartographic maps of our world, the map of science provides a bird's eye view of today's scientific landscape. It can be used to visually identify major areas of science, their size, similarity, and interconnectedness. In order to be useful, the map needs to be accurate on a local and on a global scale. While our recent work has focused on the former aspect, this paper summarizes results on how to achieve structural accuracy. Eight alternative measures of journal similarity were applied to a data set of 7,121 journals covering over 1 million documents in the combined Science Citation and Social Science Citation Indexes. For each journal similarity measure we generated two-dimensional spatial layouts using the force-directed graph layout tool, VxOrd. Next, mutual information values were calculated for each graph at different clustering levels to give a measure of structural accuracy for each map. The best co-citation and inter-citation maps according to local and structural accuracy were selected and are presented and characterized. These two maps are compared to establish robustness. The inter-citation map is then used to examine linkages between disciplines. Biochemistry appears as the most interdisciplinary discipline in science.

Langevin dynamics for ramified structures

Science.gov (United States)

Méndez, Vicenç; Iomin, Alexander; Horsthemke, Werner; Campos, Daniel

2017-06-01

We propose a generalized Langevin formalism to describe transport in combs and similar ramified structures. Our approach consists of a Langevin equation without drift for the motion along the backbone. The motion along the secondary branches may be described either by a Langevin equation or by other types of random processes. The mean square displacement (MSD) along the backbone characterizes the transport through the ramified structure. We derive a general analytical expression for this observable in terms of the probability distribution function of the motion along the secondary branches. We apply our result to various types of motion along the secondary branches of finite or infinite length, such as subdiffusion, superdiffusion, and Langevin dynamics with colored Gaussian noise and with non-Gaussian white noise. Monte Carlo simulations show excellent agreement with the analytical results. The MSD for the case of Gaussian noise is shown to be independent of the noise color. We conclude by generalizing our analytical expression for the MSD to the case where each secondary branch is n dimensional.

Structural Identification of Lentinus edodes Cellulose Derivative that ...

African Journals Online (AJOL)

... aspartic acid, leucine and alanine. Conclusion: CED was identified as a complex of peptide and polysaccharide structures possessing β- (1, 4)-glucan backbones, and it provides a theoretical basis for developing polysaccharide preparations to control aflatoxin contamination with medical and food science applications.

Long-Range Vibrational Dynamics Are Directed by Watson-Crick Base Pairing in Duplex DNA.

Science.gov (United States)

Hithell, Gordon; Shaw, Daniel J; Donaldson, Paul M; Greetham, Gregory M; Towrie, Michael; Burley, Glenn A; Parker, Anthony W; Hunt, Neil T

2016-05-05

Ultrafast two-dimensional infrared (2D-IR) spectroscopy of a 15-mer A-T DNA duplex in solution has revealed structure-dependent vibrational coupling and energy transfer processes linking bases with the sugar-phosphate backbone. Duplex melting induces significant changes in the positions of off-diagonal peaks linking carbonyl and ring-stretching vibrational modes of the adenine and thymine bases with vibrations of the phosphate group and phosphodiester linkage. These indicate that Watson-Crick hydrogen bonding and helix formation lead to a unique vibrational coupling arrangement of base vibrational modes with those of the phosphate unit. On the basis of observations from time-resolved 2D-IR data, we conclude that rapid energy transfer processes occur between base and backbone, mediated by additional modes located on the deoxyribose moiety within the same nucleotide. These relaxation dynamics are insensitive to duplex melting, showing that efficient intramolecular energy relaxation to the solvent via the phosphate groups is the key to excess energy dissipation in both single- and double-stranded DNA.

Crystal structure and conformational flexibility of the unligated FK506-binding protein FKBP12.6

Energy Technology Data Exchange (ETDEWEB)

Chen, Hui; Mustafi, Sourajit M. [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); LeMaster, David M. [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); University at Albany – SUNY, Empire State Plaza, Albany, NY 12201 (United States); Li, Zhong [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); Héroux, Annie [Brookhaven National Laboratory, Upton, NY 11973 (United States); Li, Hongmin; Hernández, Griselda, E-mail: griselda@wadsworth.org [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); University at Albany – SUNY, Empire State Plaza, Albany, NY 12201 (United States)

2014-03-01

Two crystal forms of unligated FKBP12.6 exhibit multiple conformations in the active site and in the 80s loop, the primary site for known protein-recognition interactions. The previously unreported NMR backbone assignment of FKBP12.6 revealed extensive doubling of amide resonances, which reflects a slow conformational transition centered in the 80s loop. The primary known physiological function of FKBP12.6 involves its role in regulating the RyR2 isoform of ryanodine receptor Ca{sup 2+} channels in cardiac muscle, pancreatic β islets and the central nervous system. With only a single previously reported X-ray structure of FKBP12.6, bound to the immunosuppressant rapamycin, structural inferences for this protein have been drawn from the more extensive studies of the homologous FKBP12. X-ray structures at 1.70 and 1.90 Å resolution from P2{sub 1} and P3{sub 1}21 crystal forms are reported for an unligated cysteine-free variant of FKBP12.6 which exhibit a notable diversity of conformations. In one monomer from the P3{sub 1}21 crystal form, the aromatic ring of Phe59 at the base of the active site is rotated perpendicular to its typical orientation, generating a steric conflict for the immunosuppressant-binding mode. The peptide unit linking Gly89 and Val90 at the tip of the protein-recognition ‘80s loop’ is flipped in the P2{sub 1} crystal form. Unlike the >30 reported FKBP12 structures, the backbone conformation of this loop closely follows that of the first FKBP domain of FKBP51. The NMR resonances for 21 backbone amides of FKBP12.6 are doubled, corresponding to a slow conformational transition centered near the tip of the 80s loop, as recently reported for 31 amides of FKBP12. The comparative absence of doubling for residues along the opposite face of the active-site pocket in FKBP12.6 may in part reflect attenuated structural coupling owing to increased conformational plasticity around the Phe59 ring.

Exploring backbone-cation alkyl spacers for multi-cation side chain anion exchange membranes

Science.gov (United States)

Zhu, Liang; Yu, Xuedi; Hickner, Michael A.

2018-01-01

In order to systematically study how the arrangement of cations on the side chain and length of alkyl spacers between cations impact the performance of multi-cation AEMs for alkaline fuel cells, a series of polyphenylene oxide (PPO)-based AEMs with different cationic side chains were synthesized. This work resulted in samples with two or three cations in a side chain pendant to the PPO backbone. More importantly, the length of the spacer between cations varied from 3 methylene (-CH2-) (C3) groups to 8 methylene (C8) groups. The highest conductivity, up to 99 mS/cm in liquid water at room temperature, was observed for the triple-cation side chain AEM with pentyl (C5) or hexyl (C6) spacers. The multi-cation AEMs were found to have decreased water uptake and ionic conductivity when the spacer chains between cations were lengthened from pentyl (C5) or hexyl (C6) to octyl (C8) linking groups. The triple-cation membranes with pentyl (C5) or hexyl (C6) groups between cations showed greatest stability after immersion in 1 M NaOH at 80 °C for 500 h.

Multi-Scale Modeling for Predicting the Stiffness and Strength of Hollow-Structured Metal Foams with Structural Hierarchy

Directory of Open Access Journals (Sweden)

Yong Yi

2018-03-01

Full Text Available This work was inspired by previous experiments which managed to establish an optimal template-dealloying route to prepare ultralow density metal foams. In this study, we propose a new analytical–numerical model of hollow-structured metal foams with structural hierarchy to predict its stiffness and strength. The two-level model comprises a main backbone and a secondary nanoporous structure. The main backbone is composed of hollow sphere-packing architecture, while the secondary one is constructed of a bicontinuous nanoporous network proposed to describe the nanoscale interactions in the shell. Firstly, two nanoporous models with different geometries are generated by Voronoi tessellation, then the scaling laws of the mechanical properties are determined as a function of relative density by finite volume simulation. Furthermore, the scaling laws are applied to identify the uniaxial compression behavior of metal foams. It is shown that the thickness and relative density highly influence the Young’s modulus and yield strength, and vacancy defect determines the foams being self-supported. The present study provides not only new insights into the mechanical behaviors of both nanoporous metals and metal foams, but also a practical guide for their fabrication and application.

Effects of a vanadium post-metallocene catalyst-induced polymer backbone inhomogeneity on UV oxidative degradation of the resulting polyethylene film

KAUST Repository

Atiqullah, M.; Winston, M. S.; Bercaw, J. E.; Hussain, I.; Fazal, A.; Al-Harthi, M. A.; Emwas, A. H M; Khan, M. J.; Hossaen, A.

2012-01-01

(nm-CopolyPE) with 1-hexene having very low backbone unsaturation. The nm-CopolyPE inhomogeneity was reflected in the distributions of short chain branches, 1-hexene composition, and methylene sequence length. The 1-hexene incorporation

Synthesis of branched–backbone oligosaccharides of the pectic RG-I plant cell wall polysaccharide

DEFF Research Database (Denmark)

Awan, Shahid Iqbal; Clausen, Mads Hartvig

with numerous branches of galactan, arabinan, or arabinogalactan positioned at C-4 of the rhamnose residues. The use of defined oligosaccharides rather than isolated polysaccharides can aid in obtaining detailedinformation about biosynthetic pathways, plant evolution, and agronomical properties. Furthermore......,biological testing can provide new insight into plant biology; important for plant preservation, engineering,and utilization of plants as a source of bioenergy. Present work towards defined RG-I substructures involvesa [4+3]-coupling to furnish a heptasaccharide backbone unit (see Figure 1). Moreover, installation...

Thermoresponsive Poly(2-oxazoline) Molecular Brushes by Living Ionic Polymerization: Kinetic Investigations of Pendant Chain Grafting and Cloud Point Modulation by Backbone and Side Chain Length Variation

KAUST Repository

Zhang, Ning

2012-04-17

Molecular brushes of poly(2-oxazoline)s were prepared by living anionic polymerization of 2-iso-propenyl-2-oxazoline to form the backbone and subsequent living cationic ring-opening polymerization of 2-n- or 2-iso-propyl-2-oxazoline for pendant chain grafting. In situ kinetic studies indicate that the initiation efficiency and polymerization rates are independent from the number of initiator functions per initiator molecule. This was attributed to the high efficiency of oxazolinium salt and the stretched conformation of the backbone, which is caused by the electrostatic repulsion of the oxazolinium moieties along the macroinitiator. The resulting molecular brushes showed thermoresponsive properties, that is, having a defined cloud point (CP). The dependence of the CP as a function of backbone and side chain length as well as concentration was studied. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solution structure and dynamics of melanoma inhibitory activity protein

International Nuclear Information System (INIS)

Lougheed, Julie C.; Domaille, Peter J.; Handel, Tracy M.

2002-01-01

Melanoma inhibitory activity (MIA) is a small secreted protein that is implicated in cartilage cell maintenance and melanoma metastasis. It is representative of a recently discovered family of proteins that contain a Src Homologous 3 (SH3) subdomain. While SH3 domains are normally found in intracellular proteins and mediate protein-protein interactions via recognition of polyproline helices, MIA is single-domain extracellular protein, and it probably binds to a different class of ligands.Here we report the assignments, solution structure, and dynamics of human MIA determined by heteronuclear NMR methods. The structures were calculated in a semi-automated manner without manual assignment of NOE crosspeaks, and have a backbone rmsd of 0.38 A over the ordered regions of the protein. The structure consists of an SH3-like subdomain with N- and C-terminal extensions of approximately 20 amino acids each that together form a novel fold. The rmsd between the solution structure and our recently reported crystal structure is 0.86 A over the ordered regions of the backbone, and the main differences are localized to the most dynamic regions of the protein. The similarity between the NMR and crystal structures supports the use of automated NOE assignments and ambiguous restraints to accelerate the calculation of NMR structures

Use of Just in Time Maintenance of Reinforced Concrete Bridge Structures based on Real Historical Data Deterioration Models

Directory of Open Access Journals (Sweden)

Abu-Tair A.

2016-01-01

Full Text Available Concrete is the backbone of any developed economy. Concrete can suffer from a large number of deleterious effects including physical, chemical and biological causes. Large owning bridge structures organizations are facing very serious questions when asking for maintenance budgets. The questions range from needing to justify the need for the work, its urgency, to also have to predict or show the consequences of delayed rehabilitation of a particular structure. There is therefore a need for a probabilistic model that can estimate the range of service lives of bridge populations and also the likelihood of level of deteriorations it can reached for every incremental time interval. A model was developed for such estimation based on statistical data from actual inspection records of a large reinforced concrete bridge portfolio. The method used both deterministic and stochastic methods to predict the service life of a bridge, using these service lives in combination with the just in time (JIT principle of management would enable maintenance managers to justify the need for action and the budgets needed, to intervene at the optimum time in the life of the structure and that of the deterioration. The paper will report on the model which is based on a large database of deterioration records of concrete bridges covering a period of over 60 years and include data from over 400 bridge structures. The paper will also illustrate how the service life model was developed and how these service lives combined with the JIT can be used to effectively allocate resources and use them to keep a major infrastructure asset moving with little disruption to the transport system and its users.

Perspective: Structural fluctuation of protein and Anfinsen's thermodynamic hypothesis

Science.gov (United States)

Hirata, Fumio; Sugita, Masatake; Yoshida, Masasuke; Akasaka, Kazuyuki

2018-01-01

The thermodynamics hypothesis, casually referred to as "Anfinsen's dogma," is described theoretically in terms of a concept of the structural fluctuation of protein or the first moment (average structure) and the second moment (variance and covariance) of the structural distribution. The new theoretical concept views the unfolding and refolding processes of protein as a shift of the structural distribution induced by a thermodynamic perturbation, with the variance-covariance matrix varying. Based on the theoretical concept, a method to characterize the mechanism of folding (or unfolding) is proposed. The transition state, if any, between two stable states is interpreted as a gap in the distribution, which is created due to an extensive reorganization of hydrogen bonds among back-bone atoms of protein and with water molecules in the course of conformational change. Further perspective to applying the theory to the computer-aided drug design, and to the material science, is briefly discussed.

Pressure dependence of backbone chemical shifts in the model peptides Ac-Gly-Gly-Xxx-Ala-NH2.

Science.gov (United States)

Erlach, Markus Beck; Koehler, Joerg; Crusca, Edson; Kremer, Werner; Munte, Claudia E; Kalbitzer, Hans Robert

2016-06-01

For a better understanding of nuclear magnetic resonance (NMR) detected pressure responses of folded as well as unstructured proteins the availability of data from well-defined model systems are indispensable. In this work we report the pressure dependence of chemical shifts of the backbone atoms (1)H(α), (13)C(α) and (13)C' in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (Xxx one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of these nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The polynomial pressure coefficients B 1 and B 2 are dependent on the type of amino acid studied. The coefficients of a given nucleus show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure are also weakly correlated.

Polyphosphazine-based polymer materials

Science.gov (United States)

Fox, Robert V.; Avci, Recep; Groenewold, Gary S.

2010-05-25

Methods of removing contaminant matter from porous materials include applying a polymer material to a contaminated surface, irradiating the contaminated surface to cause redistribution of contaminant matter, and removing at least a portion of the polymer material from the surface. Systems for decontaminating a contaminated structure comprising porous material include a radiation device configured to emit electromagnetic radiation toward a surface of a structure, and at least one spray device configured to apply a capture material onto the surface of the structure. Polymer materials that can be used in such methods and systems include polyphosphazine-based polymer materials having polyphosphazine backbone segments and side chain groups that include selected functional groups. The selected functional groups may include iminos, oximes, carboxylates, sulfonates, .beta.-diketones, phosphine sulfides, phosphates, phosphites, phosphonates, phosphinates, phosphine oxides, monothio phosphinic acids, and dithio phosphinic acids.

Backbone dynamics of reduced plastocyanin from the cyanobacterium Anabaena variabilis: Regions involved in electron transfer have enhanced mobility

DEFF Research Database (Denmark)

Ma, L.X.; Hass, M.A.S.; Vierick, N.

2003-01-01

The dynamics of the backbone of the electron-transfer protein plastocyanin from the cyanobacterium Anabaena variabilis were determined from the N-15 and C-13(alpha) R-1 and R-2) relaxation rates and steady-state [H-1]-N-15 and [H-1]-C-13 nuclear Overhauser effects (NOEs) using the model...

6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines.

Science.gov (United States)

Liao, Guochao; Zhou, Zhifang; Liao, Jun; Zu, Luning; Wu, Qiuye; Guo, Zhongwu

2016-02-12

With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. These glycoconjugates were proved to elicit strong IgG antibody responses in mice. It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates.

A protein-dependent side-chain rotamer library.

KAUST Repository

Bhuyan, M.S.; Gao, Xin

2011-01-01

Protein side-chain packing problem has remained one of the key open problems in bioinformatics. The three main components of protein side-chain prediction methods are a rotamer library, an energy function and a search algorithm. Rotamer libraries summarize the existing knowledge of the experimentally determined structures quantitatively. Depending on how much contextual information is encoded, there are backbone-independent rotamer libraries and backbone-dependent rotamer libraries. Backbone-independent libraries only encode sequential information, whereas backbone-dependent libraries encode both sequential and locally structural information. However, side-chain conformations are determined by spatially local information, rather than sequentially local information. Since in the side-chain prediction problem, the backbone structure is given, spatially local information should ideally be encoded into the rotamer libraries. In this paper, we propose a new type of backbone-dependent rotamer library, which encodes structural information of all the spatially neighboring residues. We call it protein-dependent rotamer libraries. Given any rotamer library and a protein backbone structure, we first model the protein structure as a Markov random field. Then the marginal distributions are estimated by the inference algorithms, without doing global optimization or search. The rotamers from the given library are then re-ranked and associated with the updated probabilities. Experimental results demonstrate that the proposed protein-dependent libraries significantly outperform the widely used backbone-dependent libraries in terms of the side-chain prediction accuracy and the rotamer ranking ability. Furthermore, without global optimization/search, the side-chain prediction power of the protein-dependent library is still comparable to the global-search-based side-chain prediction methods.

A protein-dependent side-chain rotamer library.

KAUST Repository

Bhuyan, M.S.

2011-12-14

Protein side-chain packing problem has remained one of the key open problems in bioinformatics. The three main components of protein side-chain prediction methods are a rotamer library, an energy function and a search algorithm. Rotamer libraries summarize the existing knowledge of the experimentally determined structures quantitatively. Depending on how much contextual information is encoded, there are backbone-independent rotamer libraries and backbone-dependent rotamer libraries. Backbone-independent libraries only encode sequential information, whereas backbone-dependent libraries encode both sequential and locally structural information. However, side-chain conformations are determined by spatially local information, rather than sequentially local information. Since in the side-chain prediction problem, the backbone structure is given, spatially local information should ideally be encoded into the rotamer libraries. In this paper, we propose a new type of backbone-dependent rotamer library, which encodes structural information of all the spatially neighboring residues. We call it protein-dependent rotamer libraries. Given any rotamer library and a protein backbone structure, we first model the protein structure as a Markov random field. Then the marginal distributions are estimated by the inference algorithms, without doing global optimization or search. The rotamers from the given library are then re-ranked and associated with the updated probabilities. Experimental results demonstrate that the proposed protein-dependent libraries significantly outperform the widely used backbone-dependent libraries in terms of the side-chain prediction accuracy and the rotamer ranking ability. Furthermore, without global optimization/search, the side-chain prediction power of the protein-dependent library is still comparable to the global-search-based side-chain prediction methods.

Three-Dimensional Packing Structure and Electronic Properties of Biaxially Oriented Poly(2,5-bis(3-alkylthiophene-2-yl)thieno[3,2- b ]thiophene) Films

KAUST Repository

Cho, Eunkyung

2012-04-11

We use a systematic approach that combines experimental X-ray diffraction (XRD) and computational modeling based on molecular mechanics and two-dimensional XRD simulations to develop a detailed model of the molecular-scale packing structure of poly(2,5-bis (3-tetradecylthiophene-2-yl) thieno[3,2-b]thiophene) (PBTTT-C 14) films. Both uniaxially and biaxially aligned films are used in this comparison and lead to an improved understanding of the molecular-scale orientation and crystal structure. We then examine how individual polymer components (i.e., conjugated backbone and alkyl side chains) contribute to the complete diffraction pattern, and how modest changes to a particular component orientation (e.g., backbone or side-chain tilt) influence the diffraction pattern. The effects on the polymer crystal structure of varying the alkyl side-chain length from C 12 to C 14 and C 16 are also studied. The accurate determination of the three-dimensional polymer structure allows us to examine the PBTTT electronic band structure and intermolecular electronic couplings (transfer integrals) as a function of alkyl side-chain length. This combination of theoretical and experimental techniques proves to be an important tool to help establish the relationship between the structural and electronic properties of polymer thin films. © 2012 American Chemical Society.

A ‘just-in-time’ HN(CA)CO experiment for the backbone assignment of large proteins with high sensitivity

Science.gov (United States)

Werner-Allen, Jon W.; Jiang, Ling; Zhou, Pei

2006-07-01

Among the suite of commonly used backbone experiments, HNCACO presents an unresolved sensitivity limitation due to fast 13CO transverse relaxation and passive 13Cα-13Cβ coupling. Here, we present a high-sensitivity 'just-in-time' (JIT) HN(CA)CO pulse sequence that uniformly refocuses 13Cα-13Cβ coupling while collecting 13CO shifts in real time. Sensitivity comparisons of the 3-D JIT HN(CA)CO, a CT-HMQC-based control, and a HSQC-based control with selective 13Cα inversion pulses were performed using a 2H/13C/15N labeled sample of the 29 kDa HCA II protein at 15 °C. The JIT experiment shows a 42% signal enhancement over the CT-HMQC-based experiment. Compared to the HSQC-based experiment, the JIT experiment is 16% less sensitive for residues experiencing proper 13Cα refocusing and 13Cα-13Cβ decoupling. However, for the remaining residues, the JIT spectrum shows a 106% average sensitivity gain over the HSQC-based experiment. The high-sensitivity JIT HNCACO experiment should be particularly beneficial for studies of large proteins to provide 13CO resonance information regardless of residue type.

Remote consultation and diagnosis in medical imaging using a global PACS backbone network

Science.gov (United States)

Martinez, Ralph; Sutaria, Bijal N.; Kim, Jinman; Nam, Jiseung

1993-10-01

A Global PACS is a national network which interconnects several PACS networks at medical and hospital complexes using a national backbone network. A Global PACS environment enables new and beneficial operations between radiologists and physicians, when they are located in different geographical locations. One operation allows the radiologist to view the same image folder at both Local and Remote sites so that a diagnosis can be performed. The paper describes the user interface, database management, and network communication software which has been developed in the Computer Engineering Research Laboratory and Radiology Research Laboratory. Specifically, a design for a file management system in a distributed environment is presented. In the remote consultation and diagnosis operation, a set of images is requested from the database archive system and sent to the Local and Remote workstation sites on the Global PACS network. Viewing the same images, the radiologists use pointing overlay commands, or frames to point out features on the images. Each workstation transfers these frames, to the other workstation, so that an interactive session for diagnosis takes place. In this phase, we use fixed frames and variable size frames, used to outline an object. The data pockets for these frames traverses the national backbone in real-time. We accomplish this feature by using TCP/IP protocol sockets for communications. The remote consultation and diagnosis operation has been tested in real-time between the University Medical Center and the Bowman Gray School of Medicine at Wake Forest University, over the Internet. In this paper, we show the feasibility of the operation in a Global PACS environment. Future improvements to the system will include real-time voice and interactive compressed video scenarios.

Improvement of hydrogen bond geometry in protein NMR structures by residual dipolar couplings - an assessment of the interrelation of NMR restraints

Energy Technology Data Exchange (ETDEWEB)

Jensen, Pernille Rose; Axelsen, Jacob Bock [University of Copenhagen, Institute of Molecular Biology (Denmark); Lerche, Mathilde Hauge [Amersham Health (Sweden); Poulsen, Flemming M. [University of Copenhagen, Institute of Molecular Biology (Denmark)], E-mail: fmp@apk.molbio.ku.dk

2004-01-15

We have examined how the hydrogen bond geometry in three different proteins is affected when structural restraints based on measurements of residual dipolar couplings are included in the structure calculations. The study shows, that including restraints based solely on {sup 1}H{sup N}-{sup 15}N residual dipolar couplings has pronounced impact on the backbone rmsd and Ramachandran plot but does not improve the hydrogen bond geometry. In the case of chymotrypsin inhibitor 2 the addition of {sup 13}CO-{sup 13}C{sup {alpha}} and {sup 15}N-{sup 13}CO one bond dipolar couplings as restraints in the structure calculations improved the hydrogen bond geometry to a quality comparable to that obtained in the 1.8 A resolution X-ray structure of this protein. A systematic restraint study was performed, in which four types of restraints, residual dipolar couplings, hydrogen bonds, TALOS angles and NOEs, were allowed in two states. This study revealed the importance of using several types of residual dipolar couplings to get good hydrogen bond geometry. The study also showed that using a small set of NOEs derived only from the amide protons, together with a full set of residual dipolar couplings resulted in structures of very high quality. When reducing the NOE set, it is mainly the side-chain to side-chain NOEs that are removed. Despite of this the effect on the side-chain packing is very small when a reduced NOE set is used, which implies that the over all fold of a protein structure is mainly determined by correct folding of the backbone.

Navigating the massive world of reddit: using backbone networks to map user interests in social media

Directory of Open Access Journals (Sweden)

Randal S. Olson

2015-05-01

Full Text Available In the massive online worlds of social media, users frequently rely on organizing themselves around specific topics of interest to find and engage with like-minded people. However, navigating these massive worlds and finding topics of specific interest often proves difficult because the worlds are mostly organized haphazardly, leaving users to find relevant interests by word of mouth or using a basic search feature. Here, we report on a method using the backbone of a network to create a map of the primary topics of interest in any social network. To demonstrate the method, we build an interest map for the social news web site reddit and show how such a map could be used to navigate a social media world. Moreover, we analyze the network properties of the reddit social network and find that it has a scale-free, small-world, and modular community structure, much like other online social networks such as Facebook and Twitter. We suggest that the integration of interest maps into popular social media platforms will assist users in organizing themselves into more specific interest groups, which will help alleviate the overcrowding effect often observed in large online communities.

Effects of a vanadium post-metallocene catalyst-induced polymer backbone inhomogeneity on UV oxidative degradation of the resulting polyethylene film

KAUST Repository

Atiqullah, M.

2012-07-01

A Group 5 post-metallocene precatalyst, (ONO)VCl(THF) 2 (ONO = a bis(phenolate)pyridine LX 2 pincer ligand), activated with modified methylaluminoxane (MMAO-3A) produced a linear ethylene homopolymer (nm-HomoPE)and an unusual inhomogeneous copolymer (nm-CopolyPE) with 1-hexene having very low backbone unsaturation. The nm-CopolyPE inhomogeneity was reflected in the distributions of short chain branches, 1-hexene composition, and methylene sequence length. The 1-hexene incorporation into the polyethylene backbone strongly depended on the molecular weight of the growing polymer chain. (ONO)VCl(THF) 2, because of site diversity and easier removal of a tertiary (vs. a secondary) hydrogen, produced a skewed short chain branching (SCB) profile, incorporating 1-hexene more efficiently in the low molecular weight region than in the high molecular weight region. The significant decrease in molecular weight by 1-hexene showed that the (ONO)VCl(THF) 2 catalytic sites were also highly responsive to chain-transfer directly to 1-hexene itself, producing vinyl and trans-vinylene termini. Subsequently, the effect of backbone inhomogeneity on the UV oxidative degradation of films made from both polyethylenes was investigated. The major functional group accumulated in the branched nm-CopolyPE film was carbonyl followed by carboxyl, then vinyl/ester, whereas that in the linear nm-HomoPE film was carboxyl. However, (carbonyl, carboxyl, vinyl, and ester) nm-CopolyPE film >> (carboxyl) nm-HomoPE film). The distributions of the tertiary C-H sites and methylene sequence length in the branched nm-CopolyPE film enhanced abstraction of H, decomposition of hydroperoxide group ROOH, and generation of carbonyl compounds as compared with those in the linear nm-HomoPE film. This clearly establishes the role played by the backbone inhomogeneity. The effect of short chain branches and sequence length distributions on peak melting temperature T pm, and most probably lamellar thickness L o, was

Management of Adolescent Low-Risk Classical Hodgkin Lymphoma: Which Chemotherapy Backbone Gives the Best Chance of Omitting Radiotherapy Safely.

Science.gov (United States)

Algiraigri, Ali H; Essa, Mohammed F

2016-03-01

Even though more than 90% of adolescents with low-risk classical Hodgkin lymphoma (LRcHL) will be cured with first-line therapy, many will suffer serious late toxic effects from radiotherapy (RT). The goals for care have shifted toward minimizing late toxic effects without compromising the outstanding cure rates by adapting a risk and response-based therapy. Recent published and ongoing randomized clinical trials, using functional imaging, may allow for better identification of those patients for whom RT may be safely omitted while maintaining excellent cure rates. To evaluate the best chemotherapy regimens with a reasonable toxicity profile and that are expected to have a high chance of omitting RT based on a response-directed therapy while maintaining high cure rates, a mini review was conducted of the recent clinical trials in pediatric and adult LRcHL. The UK RAPID trial chemotherapy backbone (3 × ABVD) followed by a response-based positron emission tomography scan offers up to a 75% chance of safely omitting RT without compromising the cure rate, which remained well above 90%.

Pairwise structure alignment specifically tuned for surface pockets and interaction interfaces

KAUST Repository

Cui, Xuefeng; Naveed, Hammad; Gao, Xin

2015-01-01

that are not limited to backbone fragments, and by employing a maximum weighted bipartite matching solver from the beginning of the alignment process. In addition, our methods incorporate similarities of sequentially and structurally remote residues that potentially

Pairwise structure alignment specifically tuned for surface pockets and interaction interfaces

KAUST Repository

Cui, Xuefeng

2015-09-09

To detect and evaluate the similarities between the three-dimensional (3D) structures of two molecules, various kinds of methods have been proposed for the pairwise structure alignment problem [6, 9, 7, 11]. The problem plays important roles when studying the function and the evolution of biological molecules. Recently, pairwise structure alignment methods have been extended and applied on surface pocket structures [10, 3, 5] and interaction interface structures [8, 4]. The results show that, even when there are no global similarities discovered between the global sequences and the global structures, biological molecules or complexes could share similar functions because of well conserved pockets and interfaces. Thus, pairwise pocket and interface structure alignments are promising to unveil such shared functions that cannot be discovered by the well-studied global sequence and global structure alignments. State-of-the-art methods for pairwise pocket and interface structure alignments [4, 5] are direct extensions of the classic pairwise protein structure alignment methods, and thus such methods share a few limitations. First, the goal of the classic protein structure alignment methods is to align single-chain protein structures (i.e., a single fragment of residues connected by peptide bonds). However, we observed that pockets and interfaces tend to consist of tens of extremely short backbone fragments (i.e., three or fewer residues connected by peptide bonds). Thus, existing pocket and interface alignment methods based on the protein structure alignment methods still rely on the existence of long-enough backbone fragments, and the fragmentation issue of pockets and interfaces rises the risk of missing the optimal alignments. Moreover, existing interface structure alignment methods focus on protein-protein interfaces, and require a "blackbox preprocessing" before aligning protein-DNA and protein-RNA interfaces. Therefore, we introduce the PROtein STucture Alignment

Structural Determinants of Photoreactivity of Triplex Forming Oligonucleotides Conjugated to Psoralens

Science.gov (United States)

Krishnan, Rajagopal; Oh, Dennis H.

2010-01-01

Triplex-forming oligonucleotides (TFOs) with both DNA and 2′-O-methyl RNA backbones can direct psoralen photoadducts to specific DNA sequences. However, the functional consequences of these differing structures on psoralen photoreactivity are unknown. We designed TFO sequences with DNA and 2′-O-methyl RNA backbones conjugated to psoralen by 2-carbon linkers and examined their ability to bind and target damage to model DNA duplexes corresponding to sequences within the human HPRT gene. While TFO binding affinity was not dramatically affected by the type of backbone, psoralen photoreactivity was completely abrogated by the 2′-O-methyl RNA backbone. Photoreactivity was restored when the psoralen was conjugated to the RNA TFO via a 6-carbon linker. In contrast to the B-form DNA of triplexes formed by DNA TFOs, the CD spectra of triplexes formed with 2′-O-methyl RNA TFOs exhibited features of A-form DNA. These results indicate that 2′-O-methyl RNA TFOs induce a partial B-to-A transition in their target DNA sequences which may impair the photoreactivity of a conjugated psoralen and suggest that optimal design of TFOs to target DNA damage may require a balance between binding ability and drug reactivity. PMID:20725628

Protein Structure Classification and Loop Modeling Using Multiple Ramachandran Distributions

KAUST Repository

Najibi, Seyed Morteza; Maadooliat, Mehdi; Zhou, Lan; Huang, Jianhua Z.; Gao, Xin

2017-01-01

Recently, the study of protein structures using angular representations has attracted much attention among structural biologists. The main challenge is how to efficiently model the continuous conformational space of the protein structures based on the differences and similarities between different Ramachandran plots. Despite the presence of statistical methods for modeling angular data of proteins, there is still a substantial need for more sophisticated and faster statistical tools to model the large-scale circular datasets. To address this need, we have developed a nonparametric method for collective estimation of multiple bivariate density functions for a collection of populations of protein backbone angles. The proposed method takes into account the circular nature of the angular data using trigonometric spline which is more efficient compared to existing methods. This collective density estimation approach is widely applicable when there is a need to estimate multiple density functions from different populations with common features. Moreover, the coefficients of adaptive basis expansion for the fitted densities provide a low-dimensional representation that is useful for visualization, clustering, and classification of the densities. The proposed method provides a novel and unique perspective to two important and challenging problems in protein structure research: structure-based protein classification and angular-sampling-based protein loop structure prediction.

Protein Structure Classification and Loop Modeling Using Multiple Ramachandran Distributions

KAUST Repository

Najibi, Seyed Morteza

2017-02-08

Recently, the study of protein structures using angular representations has attracted much attention among structural biologists. The main challenge is how to efficiently model the continuous conformational space of the protein structures based on the differences and similarities between different Ramachandran plots. Despite the presence of statistical methods for modeling angular data of proteins, there is still a substantial need for more sophisticated and faster statistical tools to model the large-scale circular datasets. To address this need, we have developed a nonparametric method for collective estimation of multiple bivariate density functions for a collection of populations of protein backbone angles. The proposed method takes into account the circular nature of the angular data using trigonometric spline which is more efficient compared to existing methods. This collective density estimation approach is widely applicable when there is a need to estimate multiple density functions from different populations with common features. Moreover, the coefficients of adaptive basis expansion for the fitted densities provide a low-dimensional representation that is useful for visualization, clustering, and classification of the densities. The proposed method provides a novel and unique perspective to two important and challenging problems in protein structure research: structure-based protein classification and angular-sampling-based protein loop structure prediction.

Backbone dynamics of free barnase and its complex with barstar determined by 15N NMR relaxation study

International Nuclear Information System (INIS)

Sahu, Sarata C.; Bhuyan, Abani K.; Udgaonkar, Jayant B.; Hosur, R.V.

2000-01-01

Backbone dynamics of uniformly 15 N-labeled free barnase and its complex with unlabelled barstar have been studied at 40 deg. C, pH 6.6, using 15 N relaxation data obtained from proton-detected 2D { 1 H}- 15 N NMR spectroscopy. 15 N spin-lattice relaxation rate constants (R 1 ), spin-spin relaxation rate constants (R 2 ), and steady-state heteronuclear { 1 H}- 15 N NOEs have been measured at a magnetic field strength of 14.1 Tesla for 91 residues of free barnase and for 90 residues out of a total of 106 in the complex (excluding three prolines and the N-terminal residue) backbone amide 15 N sites of barnase. The primary relaxation data for both the cases have been analyzed in the framework of the model-free formalism using both isotropic and axially symmetric models of the rotational diffusion tensor. As per the latter, the overall rotational correlation times (τ m ) are 5.0 and 9.5 ns for the free and complexed barnase, respectively. The average order parameter is found to be 0.80 for free barnase and 0.86 for the complex. However, the changes are not uniform along the backbone and for about 5 residues near the binding interface there is actually a significant decrease in the order parameters on complex formation. These residues are not involved in the actual binding. For the residues where the order parameter increases, the magnitudes vary significantly. It is observed that the complex has much less internal mobility, compared to free barnase. From the changes in the order parameters, the entropic contribution of NH bond vector motion to the free energy of complex formation has been calculated. It is apparent that these motions cause significant unfavorable contributions and therefore must be compensated by many other favorable contributions to effect tight complex formation. The observed variations in the motion and their different locations with regard to the binding interface may have important implications for remote effects and regulation of the enzyme

An improved algorithm for MFR fragment assembly

International Nuclear Information System (INIS)

Kontaxis, Georg

2012-01-01

A method for generating protein backbone models from backbone only NMR data is presented, which is based on molecular fragment replacement (MFR). In a first step, the PDB database is mined for homologous peptide fragments using experimental backbone-only data i.e. backbone chemical shifts (CS) and residual dipolar couplings (RDC). Second, this fragment library is refined against the experimental restraints. Finally, the fragments are assembled into a protein backbone fold using a rigid body docking algorithm using the RDCs as restraints. For improved performance, backbone nuclear Overhauser effects (NOEs) may be included at that stage. Compared to previous implementations of MFR-derived structure determination protocols this model-building algorithm offers improved stability and reliability. Furthermore, relative to CS-ROSETTA based methods, it provides faster performance and straightforward implementation with the option to easily include further types of restraints and additional energy terms.

Controlled Conjugated Backbone Twisting for an Increased Open-Circuit Voltage while Having a High Short-Circuit Current in Poly(hexylthiophene) Derivatives

KAUST Repository

Ko, Sangwon; Hoke, Eric T.; Pandey, Laxman; Hong, Sanghyun; Mondal, Rajib; Risko, Chad; Yi, Yuanping; Noriega, Rodrigo; McGehee, Michael D.; Bré das, Jean-Luc; Salleo, Alberto; Bao, Zhenan

2012-01-01

and charge-transfer state energy of the polymer:fullerene BHJ solar cells increased substantially with the degree of twist induced within the conjugated backbone-due to an increase in the polymer ionization potential-while the short-circuit current decreased

Structure of pectic polysaccharides from sunflower salts-soluble fraction

Science.gov (United States)

The manuscript discusses the structural features of pectin polysaccharides extracted from seedless sunflower head residues. The analysis using 1H, 13C and two-dimensional gHSQC NMR showed various numbers of methyl and hydroxyl groups attached to the anomeric carbons in the pectin backbone at differe...

Pressure dependence of backbone chemical shifts in the model peptides Ac-Gly-Gly-Xxx-Ala-NH{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Erlach, Markus Beck; Koehler, Joerg [University of Regensburg, Institute of Biophysics and Physical Biochemistry and Centre of Magnetic Resonance in Chemistry and Biomedicine (Germany); Crusca, Edson [University of São Paulo, Physics Institute of São Carlos (Brazil); Kremer, Werner [University of Regensburg, Institute of Biophysics and Physical Biochemistry and Centre of Magnetic Resonance in Chemistry and Biomedicine (Germany); Munte, Claudia E. [University of São Paulo, Physics Institute of São Carlos (Brazil); Kalbitzer, Hans Robert, E-mail: hans-robert.kalbitzer@biologie.uni-regensburg.de [University of Regensburg, Institute of Biophysics and Physical Biochemistry and Centre of Magnetic Resonance in Chemistry and Biomedicine (Germany)

2016-06-15

For a better understanding of nuclear magnetic resonance (NMR) detected pressure responses of folded as well as unstructured proteins the availability of data from well-defined model systems are indispensable. In this work we report the pressure dependence of chemical shifts of the backbone atoms {sup 1}H{sup α}, {sup 13}C{sup α} and {sup 13}C′ in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH{sub 2} (Xxx one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of these nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The polynomial pressure coefficients B{sub 1} and B{sub 2} are dependent on the type of amino acid studied. The coefficients of a given nucleus show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure are also weakly correlated.Graphical Abstract.

Analyze Of Interrelation Between Knowledge Management And Organizatıonal Structure Of Organization

OpenAIRE

MLÁDKOVÁ, Ludmila

2011-01-01

The aim of the article is to discuss interrelation between knowledge management and organizational structure of organization. Organizational structure is a backbone of the organization. Type of organizational structure used has strong impact on everyday life of organization and influences all its activities, including knowledge management. From the point of view of knowledge management, three basic groups of organizational structures can be identified in organizations; top down structures, bo...

Interplay between Peptide Bond Geometrical Parameters in Nonglobular Structural Contexts

Directory of Open Access Journals (Sweden)

Luciana Esposito

2013-01-01

Full Text Available Several investigations performed in the last two decades have unveiled that geometrical parameters of protein backbone show a remarkable variability. Although these studies have provided interesting insights into one of the basic aspects of protein structure, they have been conducted on globular and water-soluble proteins. We report here a detailed analysis of backbone geometrical parameters in nonglobular proteins/peptides. We considered membrane proteins and two distinct fibrous systems (amyloid-forming and collagen-like peptides. Present data show that in these systems the local conformation plays a major role in dictating the amplitude of the bond angle N-Cα-C and the propensity of the peptide bond to adopt planar/nonplanar states. Since the trends detected here are in line with the concept of the mutual influence of local geometry and conformation previously established for globular and water-soluble proteins, our analysis demonstrates that the interplay of backbone geometrical parameters is an intrinsic and general property of protein/peptide structures that is preserved also in nonglobular contexts. For amyloid-forming peptides significant distortions of the N-Cα-C bond angle, indicative of sterical hidden strain, may occur in correspondence with side chain interdigitation. The correlation between the dihedral angles Δω/ψ in collagen-like models may have interesting implications for triple helix stability.

Interplay between peptide bond geometrical parameters in nonglobular structural contexts.

Science.gov (United States)

Esposito, Luciana; Balasco, Nicole; De Simone, Alfonso; Berisio, Rita; Vitagliano, Luigi

2013-01-01

Several investigations performed in the last two decades have unveiled that geometrical parameters of protein backbone show a remarkable variability. Although these studies have provided interesting insights into one of the basic aspects of protein structure, they have been conducted on globular and water-soluble proteins. We report here a detailed analysis of backbone geometrical parameters in nonglobular proteins/peptides. We considered membrane proteins and two distinct fibrous systems (amyloid-forming and collagen-like peptides). Present data show that in these systems the local conformation plays a major role in dictating the amplitude of the bond angle N-C(α)-C and the propensity of the peptide bond to adopt planar/nonplanar states. Since the trends detected here are in line with the concept of the mutual influence of local geometry and conformation previously established for globular and water-soluble proteins, our analysis demonstrates that the interplay of backbone geometrical parameters is an intrinsic and general property of protein/peptide structures that is preserved also in nonglobular contexts. For amyloid-forming peptides significant distortions of the N-C(α)-C bond angle, indicative of sterical hidden strain, may occur in correspondence with side chain interdigitation. The correlation between the dihedral angles Δω/ψ in collagen-like models may have interesting implications for triple helix stability.

The ortho backbone amide linker (o-BAL) is an easily prepared and highly acid-labile handle for solid-phase synthesis

DEFF Research Database (Denmark)

Boas, Ulrik; Brask, Jesper; Christensen, J.B.

2002-01-01

The tris(alkoxy)benzyl backbone amide linker (BAL) has found widespread application in solid-phase synthesis. The key intermediate for preparation of para BAL (p-BAL) is 2,6-dimethoxy-4-hydroxybenzaldehyde; several reports on its synthesis have appeared. However, the ortho analogue of the handle (o...

A Remarkably Simple Class of Imidazolium-Based Lipids and Their Biological Properties.

Science.gov (United States)

Wang, Da; Richter, Christian; Rühling, Andreas; Drücker, Patrick; Siegmund, Daniel; Metzler-Nolte, Nils; Glorius, Frank; Galla, Hans-Joachim

2015-10-19

A series of imidazolium salts bearing two alkyl chains in the backbone of the imidazolium core were synthesized, resembling the structure of lipids. Their antibacterial activity and cytotoxicity were evaluated using Gram-positive and Gram-negative bacteria and eukaryotic cell lines including tumor cells. It is shown that the length of alkyl chains in the backbone is vital for the antibiofilm activities of these lipid-mimicking components. In addition to their biological activity, their surface activity and their membrane interactions are shown by film balance and quartz crystal microbalance (QCM) measurements. The structure-activity relationship indicates that the distinctive chemical structure contributes considerably to the biological activities of this novel class of lipids. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural characterization and immunostimulating activity of a levan-type fructan from Curcuma kwangsiensis.

Science.gov (United States)

Dong, Cai-Xia; Zhang, Li-Jiao; Xu, Rong; Zhang, Gong; Zhou, Ying-Biao; Han, Xiao-Qiang; Zhang, Ying; Sun, Yuan-Xia

2015-01-01

A fructan designated as CKNP with apparent molecular weight of 5.3kD was isolated from the hot water extract of Curcuma kwangsiensis through a combination of ion-exchange chromatography on DEAE 650M and gel filtration on Superdex G-200. CKNP was characterized by chemical derivatization as well as HPLC, GC, and GC-MS technologies. Structural studies revealed that CKNP is composed predominately of fructose (96.8%) and a small amount of glucose (3.2%) with a degree of polymerization (DP) of 30-31. It was deduced to be a levan-type fructan containing a backbone composed of (2→6)-linked β-d-Fruf residues and single β-d-Fruf residues as side chains branched at the O-1 position along the backbone. Preliminary in vitro bioactive tests on RAW 264.7 murine macrophage cells revealed that the levan-type fructan from C. kwangsiensis shows significant immunostimulating activity based on its ability to stimulate macrophage proliferation and enhance phagocytosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Data Acquisition Backbone Core DABC release v1.0

International Nuclear Information System (INIS)

Adamczewski-Musch, J; Kurz, N; Linev, S; Essel, H G

2010-01-01

The Data Acquisition Backbone Core (DABC) is a general purpose software framework designed for the implementation of a wide-range of data acquisition systems - from various small detector test beds to high performance systems. DABC consists of a compact data-flow kernel and a number of plug-ins for various functional components like data inputs, device drivers, user functional modules and applications. DABC provides configurable components for implementing event building over fast networks like InfiniBand or Gigabit Ethernet. A generic Java GUI provides the dynamic control and visualization of control parameters and commands, provided by DIM servers. A first set of application plug-ins has been implemented to use DABC as event builder for the front-end components of the GSI standard DAQ system MBS (Multi Branch System). Another application covers the connection to DAQ readout chains from detector front-end boards (N-XYTER) linked to read-out controller boards (ROC) over UDP into DABC for event building, archiving and data serving. This was applied for data taking in the September 2008 test beamtime for the CBM experiment at GSI. DABC version 1.0 is released and available from the website.

Degenerate primer MOB typing of multiresistant clinical isolates of E. coli uncovers new plasmid backbones.

Science.gov (United States)

Garcillán-Barcia, M Pilar; Ruiz del Castillo, Belén; Alvarado, Andrés; de la Cruz, Fernando; Martínez-Martínez, Luis

2015-01-01

Degenerate Primer MOB Typing is a PCR-based protocol for the classification of γ-proteobacterial transmissible plasmids in five phylogenetic relaxase MOB families. It was applied to a multiresistant E. coli collection, previously characterized by PCR-based replicon-typing, in order to compare both methods. Plasmids from 32 clinical isolates of multiresistant E. coli (19 extended spectrum beta-lactamase producers and 13 non producers) and their transconjugants were analyzed. A total of 95 relaxases were detected, at least one per isolate, underscoring the high potential of these strains for antibiotic-resistance transmission. MOBP12 and MOBF12 plasmids were the most abundant. Most MOB subfamilies detected were present in both subsets of the collection, indicating a shared mobilome among multiresistant E. coli. The plasmid profile obtained by both methods was compared, which provided useful data upon which decisions related to the implementation of detection methods in the clinic could be based. The phylogenetic depth at which replicon and MOB-typing classify plasmids is different. While replicon-typing aims at plasmid replication regions with non-degenerate primers, MOB-typing classifies plasmids into relaxase subfamilies using degenerate primers. As a result, MOB-typing provides a deeper phylogenetic depth than replicon-typing and new plasmid groups are uncovered. Significantly, MOB typing identified 17 plasmids and an integrative and conjugative element, which were not detected by replicon-typing. Four of these backbones were different from previously reported elements. Copyright © 2014 Elsevier Inc. All rights reserved.

Formatt: Correcting protein multiple structural alignments by incorporating sequence alignment

Directory of Open Access Journals (Sweden)

Daniels Noah M

2012-10-01

Full Text Available Abstract Background The quality of multiple protein structure alignments are usually computed and assessed based on geometric functions of the coordinates of the backbone atoms from the protein chains. These purely geometric methods do not utilize directly protein sequence similarity, and in fact, determining the proper way to incorporate sequence similarity measures into the construction and assessment of protein multiple structure alignments has proved surprisingly difficult. Results We present Formatt, a multiple structure alignment based on the Matt purely geometric multiple structure alignment program, that also takes into account sequence similarity when constructing alignments. We show that Formatt outperforms Matt and other popular structure alignment programs on the popular HOMSTRAD benchmark. For the SABMark twilight zone benchmark set that captures more remote homology, Formatt and Matt outperform other programs; depending on choice of embedded sequence aligner, Formatt produces either better sequence and structural alignments with a smaller core size than Matt, or similarly sized alignments with better sequence similarity, for a small cost in average RMSD. Conclusions Considering sequence information as well as purely geometric information seems to improve quality of multiple structure alignments, though defining what constitutes the best alignment when sequence and structural measures would suggest different alignments remains a difficult open question.

A modified anode/electrolyte structure for a solid oxide electrochemical cell and a method for making said structure

DEFF Research Database (Denmark)

2013-01-01

-stabilised zirconium oxide electrolyte and (c) a metallic and/or a ceramic electrocatalyst in the shape of interlayers incorporated in the interface between the anode and the electrolyte. This assembly is first sintered at a given temperature and then at a lower temperature in reducing gas mixtures. These heat...... treatments resulted in a distribution of the metallic and/or ceramic interlayers in the electrolyte/anode backbone junction taking place. The structure is prepared by (a) depositing a ceramic interlayer onto one side of the electrolyte, (b) optionally applying a metallic interlayer thereon, (c) repeating...... steps (a) and (b), (d) applying a layer of the selected anode backbone onto the electrolyte with applied interlayers, (e) sintering the raw assembly and (f) infiltrating the electrocatalyst precursor into the sintered assembly and heat treating the assembly to incorporate additional electrocatalyst...

Molecular characterization of a Penicillium chrysogenum exo-rhamnogalacturonan lyase that is structurally distinct from other polysaccharide lyase family proteins.

Science.gov (United States)

Iwai, Marin; Kawakami, Takuya; Ikemoto, Takeshi; Fujiwara, Daisuke; Takenaka, Shigeo; Nakazawa, Masami; Ueda, Mitsuhiro; Sakamoto, Tatsuji

2015-10-01

We previously described an endo-acting rhamnogalacturonan (RG) lyase, termed PcRGL4A, of Penicillium chrysogenum 31B. Here, we describe a second RG lyase, called PcRGLX. We determined the cDNA sequence of the Pcrglx gene, which encodes PcRGLX. Based on analyses using a BLAST search and a conserved domain search, PcRGLX was found to be structurally distinct from known RG lyases and might belong to a new polysaccharide lyase family together with uncharacterized fungal proteins of Nectria haematococca, Aspergillus oryzae, and Fusarium oxysporum. The Pcrglx cDNA gene product (rPcRGLX) expressed in Escherichia coli demonstrated specific activity against RG but not against homogalacturonan. Divalent cations were not essential for the enzymatic activity of rPcRGLX. rPcRGLX mainly released unsaturated galacturonosyl rhamnose (ΔGR) from RG backbones used as the substrate from the initial stage of the reaction, indicating that the enzyme can be classified as an exo-acting RG lyase (EC 4.2.2.24). This is the first report of an RG lyase with this mode of action in Eukaryota. rPcRGLX acted synergistically with PcRGL4A to degrade soybean RG and released ΔGR. This ΔGR was partially decorated with galactose (Gal) residues, indicating that rPcRGLX preferred oligomeric RGs to polymeric RGs, that the enzyme did not require Gal decoration of RG backbones for degradation, and that the enzyme bypassed the Gal side chains of RG backbones. These characteristics of rPcRGLX might be useful in the determination of complex structures of pectins.

High-resolution crystal structures of protein helices reconciled with three-centered hydrogen bonds and multipole electrostatics.

Science.gov (United States)

Kuster, Daniel J; Liu, Chengyu; Fang, Zheng; Ponder, Jay W; Marshall, Garland R

2015-01-01

Theoretical and experimental evidence for non-linear hydrogen bonds in protein helices is ubiquitous. In particular, amide three-centered hydrogen bonds are common features of helices in high-resolution crystal structures of proteins. These high-resolution structures (1.0 to 1.5 Å nominal crystallographic resolution) position backbone atoms without significant bias from modeling constraints and identify Φ = -62°, ψ = -43 as the consensus backbone torsional angles of protein helices. These torsional angles preserve the atomic positions of α-β carbons of the classic Pauling α-helix while allowing the amide carbonyls to form bifurcated hydrogen bonds as first suggested by Némethy et al. in 1967. Molecular dynamics simulations of a capped 12-residue oligoalanine in water with AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Applications), a second-generation force field that includes multipole electrostatics and polarizability, reproduces the experimentally observed high-resolution helical conformation and correctly reorients the amide-bond carbonyls into bifurcated hydrogen bonds. This simple modification of backbone torsional angles reconciles experimental and theoretical views to provide a unified view of amide three-centered hydrogen bonds as crucial components of protein helices. The reason why they have been overlooked by structural biologists depends on the small crankshaft-like changes in orientation of the amide bond that allows maintenance of the overall helical parameters (helix pitch (p) and residues per turn (n)). The Pauling 3.6(13) α-helix fits the high-resolution experimental data with the minor exception of the amide-carbonyl electron density, but the previously associated backbone torsional angles (Φ, Ψ) needed slight modification to be reconciled with three-atom centered H-bonds and multipole electrostatics. Thus, a new standard helix, the 3.6(13/10)-, Némethy- or N-helix, is proposed. Due to the use of constraints from

A Self-Assisting Protein Folding Model for Teaching Structural Molecular Biology.

Science.gov (United States)

Davenport, Jodi; Pique, Michael; Getzoff, Elizabeth; Huntoon, Jon; Gardner, Adam; Olson, Arthur

2017-04-04

Structural molecular biology is now becoming part of high school science curriculum thus posing a challenge for teachers who need to convey three-dimensional (3D) structures with conventional text and pictures. In many cases even interactive computer graphics does not go far enough to address these challenges. We have developed a flexible model of the polypeptide backbone using 3D printing technology. With this model we have produced a polypeptide assembly kit to create an idealized model of the Triosephosphate isomerase mutase enzyme (TIM), which forms a structure known as TIM barrel. This kit has been used in a laboratory practical where students perform a step-by-step investigation into the nature of protein folding, starting with the handedness of amino acids to the formation of secondary and tertiary structure. Based on the classroom evidence we collected, we conclude that these models are valuable and inexpensive resource for teaching structural molecular biology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systems and strippable coatings for decontaminating structures that include porous material

Science.gov (United States)

Fox, Robert V [Idaho Falls, ID; Avci, Recep [Bozeman, MT; Groenewold, Gary S [Idaho Falls, ID

2011-12-06

Methods of removing contaminant matter from porous materials include applying a polymer material to a contaminated surface, irradiating the contaminated surface to cause redistribution of contaminant matter, and removing at least a portion of the polymer material from the surface. Systems for decontaminating a contaminated structure comprising porous material include a radiation device configured to emit electromagnetic radiation toward a surface of a structure, and at least one spray device configured to apply a capture material onto the surface of the structure. Polymer materials that can be used in such methods and systems include polyphosphazine-based polymer materials having polyphosphazine backbone segments and side chain groups that include selected functional groups. The selected functional groups may include iminos, oximes, carboxylates, sulfonates, .beta.-diketones, phosphine sulfides, phosphates, phosphites, phosphonates, phosphinates, phosphine oxides, monothio phosphinic acids, and dithio phosphinic acids.

Vibration-based structural health monitoring of harbor caisson structure

Science.gov (United States)

Lee, So-Young; Lee, So-Ra; Kim, Jeong-Tae

2011-04-01

This study presents vibration-based structural health monitoring method in foundation-structure interface of harbor caisson structure. In order to achieve the objective, the following approaches are implemented. Firstly, vibration-based response analysis method is selected and structural health monitoring (SHM) technique is designed for harbor caisson structure. Secondly, the performance of designed SHM technique for harbor structure is examined by FE analysis. Finally, the applicability of designed SHM technique for harbor structure is evaluated by dynamic tests on a lab-scaled caisson structure.

Phylogenomics resolves a spider backbone phylogeny and rejects a prevailing paradigm for orb web evolution.

Science.gov (United States)

Bond, Jason E; Garrison, Nicole L; Hamilton, Chris A; Godwin, Rebecca L; Hedin, Marshal; Agnarsson, Ingi

2014-08-04

Spiders represent an ancient predatory lineage known for their extraordinary biomaterials, including venoms and silks. These adaptations make spiders key arthropod predators in most terrestrial ecosystems. Despite ecological, biomedical, and biomaterial importance, relationships among major spider lineages remain unresolved or poorly supported. Current working hypotheses for a spider "backbone" phylogeny are largely based on morphological evidence, as most molecular markers currently employed are generally inadequate for resolving deeper-level relationships. We present here a phylogenomic analysis of spiders including taxa representing all major spider lineages. Our robust phylogenetic hypothesis recovers some fundamental and uncontroversial spider clades, but rejects the prevailing paradigm of a monophyletic Orbiculariae, the most diverse lineage, containing orb-weaving spiders. Based on our results, the orb web either evolved much earlier than previously hypothesized and is ancestral for a majority of spiders or else it has multiple independent origins, as hypothesized by precladistic authors. Cribellate deinopoid orb weavers that use mechanically adhesive silk are more closely related to a diverse clade of mostly webless spiders than to the araneoid orb-weaving spiders that use adhesive droplet silks. The fundamental shift in our understanding of spider phylogeny proposed here has broad implications for interpreting the evolution of spiders, their remarkable biomaterials, and a key extended phenotype--the spider web. Copyright © 2014 Elsevier Ltd. All rights reserved.

Classification of pseudo pairs between nucleotide bases and amino acids by analysis of nucleotide-protein complexes.

Science.gov (United States)

Kondo, Jiro; Westhof, Eric

2011-10-01

Nucleotide bases are recognized by amino acid residues in a variety of DNA/RNA binding and nucleotide binding proteins. In this study, a total of 446 crystal structures of nucleotide-protein complexes are analyzed manually and pseudo pairs together with single and bifurcated hydrogen bonds observed between bases and amino acids are classified and annotated. Only 5 of the 20 usual amino acid residues, Asn, Gln, Asp, Glu and Arg, are able to orient in a coplanar fashion in order to form pseudo pairs with nucleotide bases through two hydrogen bonds. The peptide backbone can also form pseudo pairs with nucleotide bases and presents a strong bias for binding to the adenine base. The Watson-Crick side of the nucleotide bases is the major interaction edge participating in such pseudo pairs. Pseudo pairs between the Watson-Crick edge of guanine and Asp are frequently observed. The Hoogsteen edge of the purine bases is a good discriminatory element in recognition of nucleotide bases by protein side chains through the pseudo pairing: the Hoogsteen edge of adenine is recognized by various amino acids while the Hoogsteen edge of guanine is only recognized by Arg. The sugar edge is rarely recognized by either the side-chain or peptide backbone of amino acid residues.

Classification of pseudo pairs between nucleotide bases and amino acids by analysis of nucleotide–protein complexes

Science.gov (United States)

Kondo, Jiro; Westhof, Eric

2011-01-01

Nucleotide bases are recognized by amino acid residues in a variety of DNA/RNA binding and nucleotide binding proteins. In this study, a total of 446 crystal structures of nucleotide–protein complexes are analyzed manually and pseudo pairs together with single and bifurcated hydrogen bonds observed between bases and amino acids are classified and annotated. Only 5 of the 20 usual amino acid residues, Asn, Gln, Asp, Glu and Arg, are able to orient in a coplanar fashion in order to form pseudo pairs with nucleotide bases through two hydrogen bonds. The peptide backbone can also form pseudo pairs with nucleotide bases and presents a strong bias for binding to the adenine base. The Watson–Crick side of the nucleotide bases is the major interaction edge participating in such pseudo pairs. Pseudo pairs between the Watson–Crick edge of guanine and Asp are frequently observed. The Hoogsteen edge of the purine bases is a good discriminatory element in recognition of nucleotide bases by protein side chains through the pseudo pairing: the Hoogsteen edge of adenine is recognized by various amino acids while the Hoogsteen edge of guanine is only recognized by Arg. The sugar edge is rarely recognized by either the side-chain or peptide backbone of amino acid residues. PMID:21737431

Infiltrated SrTiO₃:FeCr‐based Anodes for Metal‐Supported SOFC

DEFF Research Database (Denmark)

Blennow Tullmar, Peter; Reddy Sudireddy, Bhaskar; Persson, Åsa Helen

2013-01-01

The concept of using electronically conducting anode backbones with subsequent infiltration of electrocatalytic active materials has been used to develop an alternative solid oxide fuel cell (SOFC) design based on a ferritic stainless steel support. The anode backbone consists of a composite made...

Dynamic Resource Allocation and QoS Control Capabilities of the Japanese Academic Backbone Network

Directory of Open Access Journals (Sweden)

Michihiro Aoki

2010-08-01

Full Text Available Dynamic resource control capabilities have become increasingly important for academic networks that must support big scientific research projects at the same time as less data intensive research and educational activities. This paper describes the dynamic resource allocation and QoS control capabilities of the Japanese academic backbone network, called SINET3, which supports a variety of academic applications with a wide range of network services. The article describes the network architecture, networking technologies, resource allocation, QoS control, and layer-1 bandwidth on-demand services. It also details typical services developed for scientific research, including the user interface, resource control, and management functions, and includes performance evaluations.

Structure of cholesterol/ceramide monolayer mixtures

DEFF Research Database (Denmark)

Scheffer, L.; Solomonov, I.; Weygand, M.J.

2005-01-01

The structure of monolayers of cholesterol/ ceramide mixtures was investigated using grazing incidence x-ray diffraction, immunofluorescence, and atomic force microscopy techniques. Grazing incidence x-ray diffraction measurements showed the existence of a crystalline mixed phase of the two....... As ceramide incorporates the lipid backbone common to all sphingolipids, this arrangement may be relevant to the understanding of the molecular organization of lipid rafts....

Dependence of crystallite formation and preferential backbone orientations on the side chain pattern in PBDTTPD polymers

KAUST Repository

El Labban, Abdulrahman

2014-11-26

(Figure Presented) Alkyl substituents appended to the π-conjugated main chain account for the solution-processability and film-forming properties of most π-conjugated polymers for organic electronic device applications, including field-effect transistors (FETs) and bulk-heterojunction (BHJ) solar cells. Beyond film-forming properties, recent work has emphasized the determining role that side-chain substituents play on polymer self-assembly and thin-film nanostructural order, and, in turn, on device performance. However, the factors that determine polymer crystallite orientation in thin-films, implying preferential backbone orientation relative to the device substrate, are a matter of some debate, and these structural changes remain difficult to anticipate. In this report, we show how systematic changes in the side-chain pattern of poly(benzo[1,2-b:4,5-b′]dithiophene-alt-thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymers can (i) influence the propensity of the polymer to order in the π-stacking direction, and (ii) direct the preferential orientation of the polymer crystallites in thin films (e.g., "face-on" vs "edge-on"). Oriented crystallites, specifically crystallites that are well-ordered in the π-stacking direction, are believed to be a key contributor to improved thin-film device performance in both FETs and BHJ solar cells.

Bistable minimum energy structures (BiMES) for binary robotics

International Nuclear Information System (INIS)

Follador, M; Conn, A T; Rossiter, J

2015-01-01

Bistable minimum energy structures (BiMES) are devices derived from the union of the concepts of dielectric elastomer minimum energy structures and bistable systems. This article presents this novel approach to active, elastic and bistable structures. BiMES are based on dielectric elastomer actuators (DEAs), which act as antagonists and provide the actuation for switching between the two equilibrium positions. A central elastic beam is the backbone of the structure and is buckled into the minimum energy configurations by the action of the two DEAs. The theory and the model of the device are presented, and also its fabrication process. BiMES are considered as fundamental units for more complex structures, which are presented and fabricated as proof of concept. Two different ways of combining the multiple units are proposed: a parallel configuration, to make a simple gripper, and a serial configuration, to generate a binary device. The possibility of using the bistable system as a continuous bender actuator, by modulating the actuation voltage of the two DEAs, was also investigated. (paper)

Effects of Tryptophan Content and Backbone Spacing on the Uptake Efficiency of Cell-Penetrating Peptides

KAUST Repository

Rydberg, Hanna A.; Matson, Maria; Å mand, Helene L.; Esbjö rner, Elin K.; Nordé n, Bengt

2012-01-01

Cell-penetrating peptides (CPPs) are able to traverse cellular membranes and deliver macromolecular cargo. Uptake occurs through both endocytotic and nonendocytotic pathways, but the molecular requirements for efficient internalization are not fully understood. Here we investigate how the presence of tryptophans and their position within an oligoarginine influence uptake mechanism and efficiency. Flow cytometry and confocal fluorescence imaging are used to estimate uptake efficiency, intracellular distribution and toxicity in Chinese hamster ovarian cells. Further, membrane leakage and lipid membrane affinity are investigated. The peptides contain eight arginine residues and one to four tryptophans, the tryptophans positioned either at the N-terminus, in the middle, or evenly distributed along the amino acid sequence. Our data show that the intracellular distribution varies among peptides with different tryptophan content and backbone spacing. Uptake efficiency is higher for the peptides with four tryptophans in the middle, or evenly distributed along the peptide sequence, than for the peptide with four tryptophans at the N-terminus. All peptides display low cytotoxicity except for the one with four tryptophans at the N-terminus, which was moderately toxic. This finding is consistent with their inability to induce efficient leakage of dye from lipid vesicles. All peptides have comparable affinities for lipid vesicles, showing that lipid binding is not a decisive parameter for uptake. Our results indicate that tryptophan content and backbone spacing can affect both the CPP uptake efficiency and the CPP uptake mechanism. The low cytotoxicity of these peptides and the possibilities of tuning their uptake mechanism are interesting from a therapeutic point of view. © 2012 American Chemical Society.

Effects of Tryptophan Content and Backbone Spacing on the Uptake Efficiency of Cell-Penetrating Peptides

KAUST Repository

Rydberg, Hanna A.

2012-07-10

Cell-penetrating peptides (CPPs) are able to traverse cellular membranes and deliver macromolecular cargo. Uptake occurs through both endocytotic and nonendocytotic pathways, but the molecular requirements for efficient internalization are not fully understood. Here we investigate how the presence of tryptophans and their position within an oligoarginine influence uptake mechanism and efficiency. Flow cytometry and confocal fluorescence imaging are used to estimate uptake efficiency, intracellular distribution and toxicity in Chinese hamster ovarian cells. Further, membrane leakage and lipid membrane affinity are investigated. The peptides contain eight arginine residues and one to four tryptophans, the tryptophans positioned either at the N-terminus, in the middle, or evenly distributed along the amino acid sequence. Our data show that the intracellular distribution varies among peptides with different tryptophan content and backbone spacing. Uptake efficiency is higher for the peptides with four tryptophans in the middle, or evenly distributed along the peptide sequence, than for the peptide with four tryptophans at the N-terminus. All peptides display low cytotoxicity except for the one with four tryptophans at the N-terminus, which was moderately toxic. This finding is consistent with their inability to induce efficient leakage of dye from lipid vesicles. All peptides have comparable affinities for lipid vesicles, showing that lipid binding is not a decisive parameter for uptake. Our results indicate that tryptophan content and backbone spacing can affect both the CPP uptake efficiency and the CPP uptake mechanism. The low cytotoxicity of these peptides and the possibilities of tuning their uptake mechanism are interesting from a therapeutic point of view. © 2012 American Chemical Society.

The first example of a Hoogsteen base-paired DNA duplex in dynamic equilibrium with a Watson-Crick base-paired duplex--a structural (NMR), kinetic and thermodynamic study.

Science.gov (United States)

Isaksson, J; Zamaratski, E; Maltseva, T V; Agback, P; Kumar, A; Chattopadhyaya, J

2001-06-01

A single-point substitution of the O4' oxygen by a CH2 group at the sugar residue of A6 (i.e. 2'-deoxyaristeromycin moiety) in a self-complementary DNA duplex, 5'-d(C1G2C3G4A5A6T7T8C9G10C11G12)2(-3), has been shown to steer the fully Watson-Crick basepaired DNA duplex (1A), akin to the native counterpart, to a doubly A6:T7 Hoogsteen basepaired (1B) B-type DNA duplex, resulting in a dynamic equilibrium of (1A)(1B): Keq = k1/k(-1) = 0.56+/-0.08. The dynamic conversion of the fully Watson-Crick basepaired (1A) to the partly Hoogsteen basepaired (1B) structure is marginally kinetically and thermodynamically disfavoured [k1 (298K) = 3.9 0.8 sec(-1); deltaHdegrees++ = 164+/-14 kJ/mol; -TdeltaS degrees++ (298K) = -92 kJ/mol giving a deltaG degrees++ 298 of 72 kJ/mol. Ea (k1) = 167 14 kJ/mol] compared to the reverse conversion of the Hoogsteen (1B) to the Watson-Crick (1A) structure [k-1 (298K) = 7.0 0.6 sec-1, deltaH degrees++ = 153 13 kJ/mol; -TdeltaSdegrees++ (298K) = -82 kJ/mol giving a deltaGdegrees++(298) of 71 kJ/mol. Ea (k-1) = 155 13 kJ/mol]. Acomparison of deltaGdegrees++(298) of the forward (k1) and backward (k-1) conversions, (1A)(1B), shows that there is ca 1 kJ/mol preference for the Watson-Crick (1A) over the double Hoogsteen basepaired (1B) DNA duplex, thus giving an equilibrium ratio of almost 2:1 in favour of the fully Watson-Crick basepaired duplex. The chemical environments of the two interconverting DNA duplexes are very different as evident from their widely separated sets of chemical shifts connected by temperature-dependent exchange peaks in the NOESY and ROESY spectra. The fully Watson-Crick basepaired structure (1A) is based on a total of 127 intra, 97 inter and 17 cross-strand distance constraints per strand, whereas the double A6:T7 Hoogsteen basepaired (1B) structure is based on 114 intra, 92 inter and 15 cross-strand distance constraints, giving an average of 22 and 20 NOE distance constraints per residue and strand, respectively. In addition

Data acquisition backbone core DABC release v1.0

Energy Technology Data Exchange (ETDEWEB)

Adamczewski-Musch, Joern; Essel, Hans G.; Kurz, Nikolaus; Linev, S. [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany)

2010-07-01

The new experiments at FAIR require new concepts of data acquisition systems for the distribution of self-triggered, time stamped data streams over high performance networks for event building. The Data Acquisition Backbone Core (DABC) is a general purpose software framework developed for the implementation of such data acquisition systems. A DABC application consists of functional components like data input, combiner, scheduler, event builder, filter, analysis and storage which can be configured at runtime. Application specific code including the support of all kinds of data channels (front-end systems) is implemented by C++ program plug-ins. DABC is also well suited as environment for various detector and readout components test beds. A set of DABC plug-ins has been developed for the FAIR experiment CBM (Compressed Baryonic Matter) at GSI. This DABC application is used as DAQ system for test beamtimes. Front-end boards equipped with n-XYTER ASICs and ADCs are connected to read-out controller boards (ROC). From there the data is sent over Ethernet (UDP), or over optics and PCIe interface cards into Linux PCs. DABC does the controlling, event building, archiving and data serving. The first release of DABC was published in 2009 and is available under GPL license.

Unambiguous Determination of Intermolecular Hydrogen Bond of NMR Structure by Molecular Dynamics Refinement Using All-Atom Force Field and Implicit Solvent Model

International Nuclear Information System (INIS)

Jee, Jun Goo

2010-01-01

It has been shown that AMD refinement is very useful for defining an intermolecular hydrogen bond in NMR structure calculation. The refined structure also provides a clue for explaining the pH dependence in Ub and UIM complexes. As reported by Choi et al., serine-mediated hydrogen bonds are the third most populated hydrogen bonds found in protein-protein intermolecular interactions, after the backbone-backbone and backbone-aspartate ones. The abundance imposes the requirement of an method to determine the interface of protein-protein complexes. The precise geometry is particularly important in the complex structures between Ub and UBDs. Ub recognizes various targets with the same surface, where both hydrophobic and hydrophobic interactions are involved. Hence, the details of the hydrophilic interactions are necessary to find the common binding modes. The structure determination of a biomolecule by NMR depends heavily on the distance restraints derived by the NOE cross peaks that are observed between two protons within 6 A through space. Therefore, the existence of the NOE peaks and their correct assignments to two corresponding protons are essential for an accurate and precise structure determination. Recent developments of NOE assignment and calculation algorithms have enabled the determination of protein 3D structures without any manual interpretation, provided chemical shifts are assigned in most atoms and sufficient NOE peaks exist. Along with these advances, the necessity of determining complicated structures such as complexes is increasing

Top-Down Hydrogen-Deuterium Exchange Analysis of Protein Structures Using Ultraviolet Photodissociation.

Science.gov (United States)

Brodie, Nicholas I; Huguet, Romain; Zhang, Terry; Viner, Rosa; Zabrouskov, Vlad; Pan, Jingxi; Petrotchenko, Evgeniy V; Borchers, Christoph H

2018-03-06

Top-down hydrogen-deuterium exchange (HDX) analysis using electron capture or transfer dissociation Fourier transform mass spectrometry (FTMS) is a powerful method for the analysis of secondary structure of proteins in solution. The resolution of the method is a function of the degree of fragmentation of backbone bonds in the proteins. While fragmentation is usually extensive near the N- and C-termini, electron capture (ECD) or electron transfer dissociation (ETD) fragmentation methods sometimes lack good coverage of certain regions of the protein, most often in the middle of the sequence. Ultraviolet photodissociation (UVPD) is a recently developed fast-fragmentation technique, which provides extensive backbone fragmentation that can be complementary in sequence coverage to the aforementioned electron-based fragmentation techniques. Here, we explore the application of electrospray ionization (ESI)-UVPD FTMS on an Orbitrap Fusion Lumos Tribrid mass spectrometer to top-down HDX analysis of proteins. We have incorporated UVPD-specific fragment-ion types and fragment-ion mixtures into our isotopic envelope fitting software (HDX Match) for the top-down HDX analysis. We have shown that UVPD data is complementary to ETD, thus improving the overall resolution when used as a combined approach.

The war of tools: how can NMR spectroscopists detect errors in their structures?

Energy Technology Data Exchange (ETDEWEB)

Saccenti, Edoardo; Rosato, Antonio [University of Florence, Magnetic Resonance Center (Italy)], E-mail: rosato@cerm.unifi.it

2008-04-15

Protein structure determination by NMR methods has started in the mid-eighties and has been growing steadily since then. Ca. 14% of the protein structures deposited in the PDB have been solved by NMR. The evaluation of the quality of NMR structures however is still lacking a well-established practice. In this work, we examined various tools for the assessment of structural quality to ascertain the extent to which these tools could be applied to detect flaws in NMR structures. In particular, we investigated the variation in the scores assigned by these programs as a function of the deviation of the structures induced by errors in assignments or in the upper distance limits used. These perturbations did not distort radically the protein fold, but resulted in backbone RMS deviations up to 3 A, which is in line with errors highlighted in the available literature. We found that it is quite difficult to discriminate the structures perturbed because of misassignments from the original ones, also because the spread in score over the conformers of the original bundle is relatively large. {phi}-{psi} distributions and normality scores related to the backbone conformation and to the distribution of side-chain dihedral angles are the most sensitive indicators of flaws.

Solid state radiation chemistry of the DNA backbone

International Nuclear Information System (INIS)

Bernhard, W.A.

1989-09-01

The long term goal of this program is to determine the fundamental rules needed to predict the type and yield of damage produced in DNA due to direct effects of ionizing radiation. The focus is on damage to the sugar-phosphate backbone, damage that would lead to strand breaks. Model systems have been chosen that permit various aspects of this problem to be investigated. The emphasis will be on single crystals of monosaccharides, nucleosides, and nucleotides but will also include some powder work on polynucleotides. In these model systems, free radical products and reactions are observed by electron spin resonance (ESR) and electron nuclear double resonance (ENDOR) techniques. The information thus gained is used in constructing rules that predict what primary free radicals are formed in single crystals of model compounds and the reactions stemming from the primary radicals. The formulation of a set of rules that work in model systems will represent a major advance toward formulating a set of rules that predict the direct damage in DNA itself. In a broader context this program is part of the effort to understand and predict the effects of exposure to ionizing radiation received at low dose rates over long periods of time. Assessment of low dose effects requires a basic understanding of the action of radiation at the molecular level. By contributing to that basic understanding, this program will help solve the problems of risk assessment under low dose conditions. 5 refs., 3 figs

Computing a new family of shape descriptors for protein structures

DEFF Research Database (Denmark)

Røgen, Peter; Sinclair, Robert

2003-01-01

The large-scale 3D structure of a protein can be represented by the polygonal curve through the carbon a atoms of the protein backbone. We introduce an algorithm for computing the average number of times that a given configuration of crossings on such polygonal curves is seen, the average being...

1H NMR studies of plastocyanin from Scenedesmus obliquus: Complete sequence-specific assignment, secondary structure analysis, and global fold

International Nuclear Information System (INIS)

Moore, J.M.; Chazin, W.J.; Wright, P.E.; Powls, R.

1988-01-01

Two-dimensional 1 H NMR methods have been used to make sequence-specific resonance assignments for the 97 amino acid residues of the plastocyanin from the green alga Scenedesmus obliquus. Assignments were obtained for all backbone protons and the majority of the side-chain protons. Spin system identification relied heavily on the observation of relayed connectivities to the backbone amide proton. Sequence-specific assignments were made by using the sequential assignment procedure. During this process, an extra valine residue was identified that had not been detected in the original amino acid sequence. Elements of regular secondary structure were identified from characteristic NOE connectivities between backbone protons, coupling constant values, and the observation of slowly exchanging amide protons. The protein in solution contains eight β-strands, one short segment of helix, five reverse turns, and five loops. The β-strands may be arranged into two βsheets on the basis of extensive cross-strand NOE connectivities. The chain-folding topology determined from the NMR experiments is that of a Greek key β-barrel and is similar to that observed for French bean plastocyanin in solution and poplar plastocyanin in the crystalline state. While the overall structures are similar, several differences in local structure between the S. obliquus and higher plant plastocyanins have been identified

¹H, ¹³C, and ¹⁵N backbone and side-chain chemical shift assignment of the toxin Doc in the unbound state.

Science.gov (United States)

De Gieter, Steven; Loris, Remy; van Nuland, Nico A J; Garcia-Pino, Abel

2014-04-01

Toxin-antitoxin (TA) modules in bacteria are involved in pathogenesis, antibiotic stress response, persister formation and programmed cell death. The toxin Doc, from the phd/doc module, blocks protein synthesis by targeting the translation machinery. Despite a large wealth of biophysical and biochemical data on the regulatory aspects of the operon transcription and role of Doc co-activator and co-repressor, little is still know on the molecular basis of Doc toxicity. Structural information about this toxin is only available for its inhibited state bound to the antitoxin Phd. Here we report the (1)H, (15)N and (13)C backbone and side chain chemical shift assignments of the toxin Doc from of bacteriophage P1 (the model protein from this family of TA modules) in its free state. The BMRB accession number is 18899.

Double-Stranded Peptide Nucleic Acids

DEFF Research Database (Denmark)

2001-01-01

A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.......A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Modulation of Cellular Transcription Factor Activity

DEFF Research Database (Denmark)

2003-01-01

A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.......A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Revealing the Linkage Network Dynamic Structures of Chinese Maritime Ports through Automatic Information System Data

Directory of Open Access Journals (Sweden)

Hongchu Yu

2017-10-01

Full Text Available Marine economic cooperation has emerged as a major theme in this era of globalization; hence, maritime network connectivity and dynamics have attracted more and more attention. Port construction and maritime route improvements increase maritime trade and thus facilitate economic viability and resource sustainability. This paper reveals the regional dimension of inter-port linkage dynamic structure of Chinese maritime ports from a complex multilayer perspective that is meaningful for strategic forecasting and regional long-term economic development planning. In this research, Automatic Information System (AIS-derived traffic flows were used to construct a maritime network and subnetworks based on the geographical locations of ports. The linkage intensity between subnetworks, the linkage tightness within subnetworks, the spatial isolation between high-intensity backbones and tight skeleton networks, and a linkage concentration index for each port were calculated. The ports, in turn, were analyzed based on these network attributes. This study analyzed the external competitiveness and internal cohesion of each subnetwork. The results revealed problems in port management and planning, such as unclear divisions in port operations. More critically, weak complementary relationships between the backbone and skeleton networks among the ports reduce connectivity and must be strengthened. This research contributes to the body of work supporting strategic decision-making for future development.

Extensive Air Showers: from the muonic smoking guns to the hadronic backbone

Directory of Open Access Journals (Sweden)

Cazon L.

2013-06-01

Full Text Available Extensive Air Showers are complex macroscopic objects initiated by single ultra-high energy particles. They are the result of millions of high energy reactions in the atmosphere and can be described as the superposition of hadronic and electromagnetic cascades. The hadronic cascade is the air shower backbone, and it is mainly made of pions. Decays of neutral pions initiate electromagnetic cascades, while the decays of charged pions produce muons which leave the hadronic core and travel many kilometers almost unaffected. Muons are smoking guns of the hadronic cascade: the energy, transverse momentum, spatial distribution and depth of production are key to reconstruct the history of the air shower. In this work, we overview the phenomenology of muons on the air shower and its relation to the hadronic cascade. We briefly review the experimental efforts to analyze muons within air showers and discuss possible paths to use this information.

Application of 13C-labeling and 13C-13C COSY NMR experiments in the structure determination of a microbial natural product.

Science.gov (United States)

Kwon, Yun; Park, Sunghyouk; Shin, Jongheon; Oh, Dong-Chan

2014-08-01

The elucidation of the structures of complex natural products bearing many quaternary carbons remains challenging, even in this advanced spectroscopic era. (13)C-(13)C COSY NMR spectroscopy shows direct couplings between (13)C and (13)C, which comprise the backbone of a natural product. Thus, this type of experiment is particularly useful for natural products bearing consecutive quaternary carbons. However, the low sensitivity of (13)C-based NMR experiments, due to the low natural abundance of the (13)C nucleus, is problematic when applying these techniques. Our efforts in the (13)C labeling of a microbial natural product, cyclopiazonic acid (1), by feeding (13)C-labeled glucose to the fungal culture, enabled us to acquire (13)C-(13)C COSY NMR spectra on a milligram scale that clearly show the carbon backbone of the compound. This is the first application of (13)C-(13)C COSY NMR experiments for a natural product. The results suggest that (13)C-(13)C COSY NMR spectroscopy can be routinely used for the structure determination of microbial natural products by (13)C-enrichment of a compound with (13)C-glucose.

Heterogeneity to Homogeneity: Synthesis, Base Pairing, and Ligation Studies of 4',3'-XyluloNA/RNA and TNA/RNA Chimeric Sequences

Science.gov (United States)

Bhowmik, S.; Stoop, M.; Krishnamurthy, R.

2017-07-01

Based on the reality of "prebiotic clutter," we herein present an alternate model for pre-RNA to RNA transition, which starts, not with homogeneous-backbone system, but rather with mixtures of heterogeneous-backbone of chimeric "pre-RNA/RNA."

Collective estimation of multiple bivariate density functions with application to angular-sampling-based protein loop modeling

KAUST Repository

Maadooliat, Mehdi

2015-10-21

This paper develops a method for simultaneous estimation of density functions for a collection of populations of protein backbone angle pairs using a data-driven, shared basis that is constructed by bivariate spline functions defined on a triangulation of the bivariate domain. The circular nature of angular data is taken into account by imposing appropriate smoothness constraints across boundaries of the triangles. Maximum penalized likelihood is used to fit the model and an alternating blockwise Newton-type algorithm is developed for computation. A simulation study shows that the collective estimation approach is statistically more efficient than estimating the densities individually. The proposed method was used to estimate neighbor-dependent distributions of protein backbone dihedral angles (i.e., Ramachandran distributions). The estimated distributions were applied to protein loop modeling, one of the most challenging open problems in protein structure prediction, by feeding them into an angular-sampling-based loop structure prediction framework. Our estimated distributions compared favorably to the Ramachandran distributions estimated by fitting a hierarchical Dirichlet process model; and in particular, our distributions showed significant improvements on the hard cases where existing methods do not work well.

Collective estimation of multiple bivariate density functions with application to angular-sampling-based protein loop modeling

KAUST Repository

Maadooliat, Mehdi; Zhou, Lan; Najibi, Seyed Morteza; Gao, Xin; Huang, Jianhua Z.

2015-01-01

This paper develops a method for simultaneous estimation of density functions for a collection of populations of protein backbone angle pairs using a data-driven, shared basis that is constructed by bivariate spline functions defined on a triangulation of the bivariate domain. The circular nature of angular data is taken into account by imposing appropriate smoothness constraints across boundaries of the triangles. Maximum penalized likelihood is used to fit the model and an alternating blockwise Newton-type algorithm is developed for computation. A simulation study shows that the collective estimation approach is statistically more efficient than estimating the densities individually. The proposed method was used to estimate neighbor-dependent distributions of protein backbone dihedral angles (i.e., Ramachandran distributions). The estimated distributions were applied to protein loop modeling, one of the most challenging open problems in protein structure prediction, by feeding them into an angular-sampling-based loop structure prediction framework. Our estimated distributions compared favorably to the Ramachandran distributions estimated by fitting a hierarchical Dirichlet process model; and in particular, our distributions showed significant improvements on the hard cases where existing methods do not work well.

A Refined Model for the Structure of Acireductone Dioxygenase from Klebsiella ATCC 8724 Incorporating Residual Dipolar Couplings

Energy Technology Data Exchange (ETDEWEB)

Pochapsky, Thomas C., E-mail: pochapsk@brandeis.edu; Pochapsky, Susan S.; Ju Tingting [Brandeis University, Department of Chemistry (United States); Hoefler, Chris [Brandeis University, Department of Biochemistry (United States); Liang Jue [Brandeis University, Department of Chemistry (United States)

2006-02-15

Acireductone dioxygenase (ARD) from Klebsiella ATCC 8724 is a metalloenzyme that is capable of catalyzing different reactions with the same substrates (acireductone and O{sub 2}) depending upon the metal bound in the active site. A model for the solution structure of the paramagnetic Ni{sup 2+}-containing ARD has been refined using residual dipolar couplings (RDCs) measured in two media. Additional dihedral restraints based on chemical shift (TALOS) were included in the refinement, and backbone structure in the vicinity of the active site was modeled from a crystallographic structure of the mouse homolog of ARD. The incorporation of residual dipolar couplings into the structural refinement alters the relative orientations of several structural features significantly, and improves local secondary structure determination. Comparisons between the solution structures obtained with and without RDCs are made, and structural similarities and differences between mouse and bacterial enzymes are described. Finally, the biological significance of these differences is considered.

SCit: web tools for protein side chain conformation analysis

OpenAIRE

Gautier, R.; Camproux, A.-C.; Tufféry, P.

2004-01-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each...

Suppression of acyl migration in enzymatic production of structured lipids through temperature programming

DEFF Research Database (Denmark)

Yang, Tiankui; Fruekilde, Maj-Britt; Xu, Xuebing

2005-01-01

Acyl migration in the glycerol backbone often leads to the increase of by-products in the enzymatic production of specific structured lipids. Acyl migration is a thermodynamic process and is very difficult to stop fully in actual reactions. The objective of this study was to investigate...

pi-Turns: types, systematics and the context of their occurrence in protein structures.

Science.gov (United States)

Dasgupta, Bhaskar; Chakrabarti, Pinak

2008-09-22

For a proper understanding of protein structure and folding it is important to know if a polypeptide segment adopts a conformation inherent in the sequence or it depends on the context of its flanking secondary structures. Turns of various lengths have been studied and characterized starting from three-residue gamma-turn to six-residue pi-turn. The Schellman motif occurring at the C-terminal end of alpha-helices is a classical example of hydrogen bonded pi-turn involving residues at (i) and (i+5) positions. Hydrogen bonded and non-hydrogen bonded beta- and alpha-turns have been identified previously; likewise, a systematic characterization of pi-turns would provide valuable insight into turn structures. An analysis of protein structures indicates that at least 20% of pi-turns occur independent of the Schellman motif. The two categories of pi-turns, designated as pi-HB and SCH, have been further classified on the basis of backbone conformation and both have AAAa as the major class. They differ in the residue usage at position (i+1), the former having a large preference for Pro that is absent in the latter. As in the case of shorter length beta- and alpha-turns, pi-turns have also been identified not only on the basis of the existence of hydrogen bond, but also using the distance between terminal C alpha-atoms, and this resulted in a comparable number of non-hydrogen-bonded pi-turns (pi-NHB). The presence of shorter beta- and alpha-turns within all categories of pi-turns, the subtle variations in backbone torsion angles along the turn residues, the location of the turns in the context of tertiary structures have been studied. pi-turns have been characterized, first using hydrogen bond and the distance between C alpha atoms of the terminal residues, and then using backbone torsion angles. While the Schellman motif has a structural role in helix termination, many of the pi-HB turns, being located on surface cavities, have functional role and there is also sequence

J-UNIO protocol used for NMR structure determination of the 206-residue protein NP-346487.1 from Streptococcus pneumoniae TIGR4

Energy Technology Data Exchange (ETDEWEB)

Jaudzems, Kristaps [Latvian Institute of Organic Synthesis (Latvia); Pedrini, Bill [Paul Scherrer Institute (PSI), SwissFEL Project (Switzerland); Geralt, Michael; Serrano, Pedro; Wüthrich, Kurt, E-mail: wuthrich@scripps.edu [The Scripps Research Institute, Department of Integrative Structural and Computational Biology (United States)

2015-01-15

The NMR structure of the 206-residue protein NP-346487.1 was determined with the J-UNIO protocol, which includes extensive automation of the structure determination. With input from three APSY-NMR experiments, UNIO-MATCH automatically yielded 77 % of the backbone assignments, which were interactively validated and extended to 97 %. With an input of the near-complete backbone assignments and three 3D heteronuclear-resolved [{sup 1}H,{sup 1}H]-NOESY spectra, automated side chain assignment with UNIO-ATNOS/ASCAN resulted in 77 % of the expected assignments, which was extended interactively to about 90 %. Automated NOE assignment and structure calculation with UNIO-ATNOS/CANDID in combination with CYANA was used for the structure determination of this two-domain protein. The individual domains in the NMR structure coincide closely with the crystal structure, and the NMR studies further imply that the two domains undergo restricted hinge motions relative to each other in solution. NP-346487.1 is so far the largest polypeptide chain to which the J-UNIO structure determination protocol has successfully been applied.

Data Dissemination Based on Fuzzy Logic and Network Coding in Vehicular Networks

Directory of Open Access Journals (Sweden)

Xiaolan Tang

2017-01-01

Full Text Available Vehicular networks, as a significant technology in intelligent transportation systems, improve the convenience, efficiency, and safety of driving in smart cities. However, because of the high velocity, the frequent topology change, and the limited bandwidth, it is difficult to efficiently propagate data in vehicular networks. This paper proposes a data dissemination scheme based on fuzzy logic and network coding for vehicular networks, named SFN. It uses fuzzy logic to compute a transmission ability for each vehicle by comprehensively considering the effects of three factors: the velocity change rate, the velocity optimization degree, and the channel quality. Then, two nodes with high abilities are selected as primary backbone and slave backbone in every road segment, which propagate data to other vehicles in this segment and forward them to the backbones in the next segment. The backbone network helps to increase the delivery ratio and avoid invalid transmissions. Additionally, network coding is utilized to reduce transmission overhead and accelerate data retransmission in interbackbone forwarding and intrasegment broadcasting. Experiments show that, compared with existing schemes, SFN has a high delivery ratio and a short dissemination delay, while the backbone network keeps high reliability.

Protein structure validation and refinement using amide proton chemical shifts derived from quantum mechanics

DEFF Research Database (Denmark)

Christensen, Anders Steen; Linnet, Troels Emtekær; Borg, Mikael

2013-01-01

We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts - sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level...

Integral membrane protein structure determination using pseudocontact shifts

Energy Technology Data Exchange (ETDEWEB)

Crick, Duncan J.; Wang, Jue X. [University of Cambridge, Department of Biochemistry (United Kingdom); Graham, Bim; Swarbrick, James D. [Monash University, Monash Institute of Pharmaceutical Sciences (Australia); Mott, Helen R.; Nietlispach, Daniel, E-mail: dn206@cam.ac.uk [University of Cambridge, Department of Biochemistry (United Kingdom)

2015-04-15

Obtaining enough experimental restraints can be a limiting factor in the NMR structure determination of larger proteins. This is particularly the case for large assemblies such as membrane proteins that have been solubilized in a membrane-mimicking environment. Whilst in such cases extensive deuteration strategies are regularly utilised with the aim to improve the spectral quality, these schemes often limit the number of NOEs obtainable, making complementary strategies highly beneficial for successful structure elucidation. Recently, lanthanide-induced pseudocontact shifts (PCSs) have been established as a structural tool for globular proteins. Here, we demonstrate that a PCS-based approach can be successfully applied for the structure determination of integral membrane proteins. Using the 7TM α-helical microbial receptor pSRII, we show that PCS-derived restraints from lanthanide binding tags attached to four different positions of the protein facilitate the backbone structure determination when combined with a limited set of NOEs. In contrast, the same set of NOEs fails to determine the correct 3D fold. The latter situation is frequently encountered in polytopical α-helical membrane proteins and a PCS approach is thus suitable even for this particularly challenging class of membrane proteins. The ease of measuring PCSs makes this an attractive route for structure determination of large membrane proteins in general.

Probing structure-antifouling activity relationships of polyacrylamides and polyacrylates.

Science.gov (United States)

Zhao, Chao; Zhao, Jun; Li, Xiaosi; Wu, Jiang; Chen, Shenfu; Chen, Qiang; Wang, Qiuming; Gong, Xiong; Li, Lingyan; Zheng, Jie

2013-07-01

We have synthesized two different polyacrylamide polymers with amide groups (polySBAA and polyHEAA) and two corresponding polyacrylate polymers without amide groups (polySBMA and polyHEA), with particular attention to the evaluation of the effect of amide group on the hydration and antifouling ability of these systems using both computational and experimental approaches. The influence of polymer architectures of brushes, hydrogels, and nanogels, prepared by different polymerization methods, on antifouling performance is also studied. SPR and ELISA data reveal that all polymers exhibit excellent antifouling ability to repel proteins from undiluted human blood serum/plasma, and such antifouling ability can be further enhanced by presenting amide groups in polySBAA and polyHEAA as compared to polySBMA and polyHEA. The antifouling performance is positively correlated with the hydration properties. Simulations confirm that four polymers indeed have different hydration characteristics, while all presenting a strong hydration overall. Integration of amide group with pendant hydroxyl or sulfobetaine group in polymer backbones is found to increase their surface hydration of polymer chains and thus to improve their antifouling ability. Importantly, we present a proof-of-concept experiment to synthesize polySBAA nanogels, which show a switchable property between antifouling and pH-responsive functions driven by acid-base conditions, while still maintaining high stability in undiluted fetal bovine serum and minimal toxicity to cultured cells. This work provides important structural insights into how very subtle structural changes in polymers can yield great improvement in biological activity, specifically the inclusion of amide group in polymer backbone/sidechain enables to obtain antifouling materials with better performance for biomedical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Specific-structured lipids: nutritional perspectives and production potentials

DEFF Research Database (Denmark)

Xu, Xuebing; Høy, Carl-Erik; Balchen, Steen

1997-01-01

Structured lipids are referring to any triacylglycerols containing both long chain fatty acids (mostly essential fatty acids) and medium or short chain fatty acids. In case of specific-structured lipids (SSLs), each group of fatty acids locates specifically at sn-2 or -1.3 positions of the glycerol...... backbone. Recently the nutritional perspectives of this kind of lipids attract many interests. This causes an increasing interest in the production of them by lipase-catalyzed interesterification. One of the advantages of lipase method over chemical ones is that SSLs can be produced with particular fatty...

New insights into structure and function of the different types of fatty acid-binding protein

NARCIS (Netherlands)

Zimmerman, Augusta Wilhelmina

2002-01-01

Fatty acid binding proteins (FABPs) are small cytosolic proteins with virtually identical backbone structures that facilitate the solubility and intracellular transport of fatty acids. They may also modulate the effect of fatty acids on various metabolic enzymes and receptors and on cellular

Synthesis of Polystyrene-Based Random Copolymers with Balanced Number of Basic or Acidic Functional Groups

DEFF Research Database (Denmark)

Dimitrov, Ivaylo; Jankova Atanasova, Katja; Hvilsted, Søren

2010-01-01

for the functionalization were applied. The first one involved direct functionalization of the template backbone through alkylation of the phenolic groups with suitable reagents. The second modification approach was based on "click" chemistry, where the introduction of alkyne groups onto the template backbone was followed......Pairs of polystyrene-based random copolymers with balanced number of pendant basic or acidic groups were synthesized utilizing the template strategy. The same poly[(4-hydroxystyrene)-ran-styrene] was used as a template backbone for modification. Two different synthetic approaches...... by copper-catalyzed 1,3 cycloaddition of aliphatic sulfonate- or amine-contaning azides. Both synthetic approaches proved to be highly efficient as evidenced by H-1-NMR analyses. The thermal properties were evaluated by differential scanning calorimetry and thermal gravimetric analyses and were influenced...

Structural characterisation of galactoglucomannan secreted by suspension-cultured cells of Nicotiana plumbaginifolia.

Science.gov (United States)

Sims, I M; Craik, D J; Bacic, A

1997-08-25

Galactoglucomannan (GGM) from cultures of Nicotiana plumbaginifolia has Man:Glc:Gal:Ara:Xyl in 1.0:1.1:1.0:0.1:0.04 ratio. Linkage analysis contained 4- and 4,6-Manp, 4-Glcp, terminal Galp and 2-Galp, small amounts and terminal Arap and terminal Xylp, and approximately 0.03 mol acetyl per mol of glucosyl residue. Treatment with alpha- and beta-D-galactosidases showed that the majority of the side-chains were either single Galp-alpha-(1-->residues or the disaccharide Galp-beta-(1-->2)-Galp-alpha-(1-->linked to O-6 of the 4-Manp residues of the glucomannan backbone. Analysis of the oligosaccharides generated by endo-(1-->4)-beta-mannanase digestion confirmed that the GGM comprises a backbone of predominantly alternating-->4)-D-Manp-beta-(1-->and-->4)-D-Glcp-beta-(1-->branch ed at O-6 of 65% of the 4-Manp residues. The major oligosaccharide identified was D-Glcp-beta-(1-->4)-[D-Galp-beta-(1-->2)-D-Galp-alpha-(1-->6)]-D-Man p-beta-(1-->4)-D-Glcp-beta-(1-->4)-[D-Galp-alpha-(1-->6)]-D-Manp -beta-(1-->(27%), and most of the other oligosaccharides produced in significant quantities were based on this structure.

Quantitative comparison of structure and dynamics of elastin following three isolation schemes by 13C solid state NMR and MALDI mass spectrometry.

Science.gov (United States)

Papaioannou, A; Louis, M; Dhital, B; Ho, H P; Chang, E J; Boutis, G S

2015-05-01

Methods for isolating elastin from fat, collagen, and muscle, commonly used in the design of artificial elastin based biomaterials, rely on exposing tissue to harsh pH levels and temperatures that usually denature many proteins. At present, a quantitative measurement of the modifications to elastin following isolation from other extracellular matrix constituents has not been reported. Using magic angle spinning (13)C NMR spectroscopy and relaxation methodologies, we have measured the modification in structure and dynamics following three known purification protocols. Our experimental data reveal that the (13)C spectra of the hydrated samples appear remarkably similar across the various purification methods. Subtle differences in the half maximum widths were observed in the backbone carbonyl suggesting possible structural heterogeneity across the different methods of purification. Additionally, small differences in the relative signal intensities were observed between purified samples. Lyophilizing the samples results in a reduction of backbone motion and reveals additional differences across the purification methods studied. These differences were most notable in the alanine motifs indicating possible changes in cross-linking or structural rigidity. The measured correlation times of glycine and proline moieties are observed to also vary considerably across the different purification methods, which may be related to peptide bond cleavage. Lastly, the relative concentration of desmosine cross-links in the samples quantified by MALDI mass spectrometry is reported. Copyright © 2015 Elsevier B.V. All rights reserved.

Real-time prediction of atmospheric Lagrangian coherent structures based on forecast data: An application and error analysis

Science.gov (United States)

BozorgMagham, Amir E.; Ross, Shane D.; Schmale, David G.

2013-09-01

The language of Lagrangian coherent structures (LCSs) provides a new means for studying transport and mixing of passive particles advected by an atmospheric flow field. Recent observations suggest that LCSs govern the large-scale atmospheric motion of airborne microorganisms, paving the way for more efficient models and management strategies for the spread of infectious diseases affecting plants, domestic animals, and humans. In addition, having reliable predictions of the timing of hyperbolic LCSs may contribute to improved aerobiological sampling of microorganisms with unmanned aerial vehicles and LCS-based early warning systems. Chaotic atmospheric dynamics lead to unavoidable forecasting errors in the wind velocity field, which compounds errors in LCS forecasting. In this study, we reveal the cumulative effects of errors of (short-term) wind field forecasts on the finite-time Lyapunov exponent (FTLE) fields and the associated LCSs when realistic forecast plans impose certain limits on the forecasting parameters. Objectives of this paper are to (a) quantify the accuracy of prediction of FTLE-LCS features and (b) determine the sensitivity of such predictions to forecasting parameters. Results indicate that forecasts of attracting LCSs exhibit less divergence from the archive-based LCSs than the repelling features. This result is important since attracting LCSs are the backbone of long-lived features in moving fluids. We also show under what circumstances one can trust the forecast results if one merely wants to know if an LCS passed over a region and does not need to precisely know the passage time.

Live Virus Vaccines Based on a Yellow Fever Vaccine Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment*

Science.gov (United States)

Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called “chimeric virus vaccines”). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were replaced by the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

Science.gov (United States)

Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

Probing the structural dependence of carbon space lengths of poly(N-hydroxyalkyl acrylamide)-based brushes on antifouling performance.

Science.gov (United States)

Yang, Jintao; Zhang, Mingzhen; Chen, Hong; Chang, Yung; Chen, Zhan; Zheng, Jie

2014-08-11

Numerous biocompatible antifouling polymers have been developed for a wide variety of fundamental and practical applications in drug delivery, biosensors, marine coatings, and many other areas. Several antifouling mechanisms have been proposed, but the exact relationship among molecular structure, surface hydration property, and antifouling performance of antifouling polymers still remains elusive. Here this work strives to provide a better understanding of the structure-property relationship of poly(N-hydroxyalkyl acrylamide)-based materials. We have designed, synthesized, and characterized a series of polyHAAA brushes of various carbon spacer lengths (CSLs), that is, poly(N-hydroxymethyl acrylamide) (polyHMAA), poly(N-(2-hydroxyethyl)acrylamide) (polyHEAA), poly(N-(3-hydroxypropyl)acrylamide) (polyHPAA), and poly(N-(5-hydroxypentyl)acrylamide) (polyHPenAA), to study the structural dependence of CSLs on their antifouling performance. HMAA, HEAA, HPAA, and HPenAA monomers contained one, two, three, and five methylene groups between hydroxyl and amide groups, while the other groups in polymer backbones were the same as each other. The relation of such small structural differences of polymer brushes to their surface hydration and antifouling performance was studied by combined experimental and computational methods including surface plasmon resonance sensors, sum frequency generation (SFG) vibrational spectroscopy, cell adhesion assay, and molecular simulations. Antifouling results showed that all polyHAAA-based brushes were highly surface resistant to protein adsorption from single protein solutions, undiluted blood serum and plasma, as well as cell adhesion up to 7 days. In particular, polyHMAA and polyHEAA with the shorter CSLs exhibited higher surface hydration and better antifouling ability than polyHPMA and polyHPenAA. SFG and molecular simulations further revealed that the variation of CSLs changed the ratio of hydrophobicity/hydrophilicity of polymers

Automated assignment and 3D structure calculations using combinations of 2D homonuclear and 3D heteronuclear NOESY spectra

International Nuclear Information System (INIS)

Oezguen, Numan; Adamian, Larisa; Xu Yuan; Rajarathnam, Krishna; Braun, Werner

2002-01-01

The NOAH/DIAMOD suite uses feedback filtering and self-correcting distance geometry to generate 3D structures from unassigned NOESY spectra. In this study we determined the minimum set of experiments needed to generate a high quality structure bundle. Different combinations of 3D 15 N-edited, 13 C-edited HSQC-NOESY and 2D homonuclear 1 H- 1 H NOESY spectra of the 77 amino acid protein, myeloid progenitor inhibitory factor-1 (MPIF-1) were used as input for NOAH/DIAMOD calculations. The quality of the assignments of NOESY cross peaks and the accuracy of the automatically generated 3D structures were compared to those obtained with a conventional manual procedure. Combining data from two types of experiments synergistically increased the number of peaks assigned unambiguously in both individual spectra. As a general trend for the accuracy of the structures we observed structural variations in the backbone fold of the final structures of about 2 A for single spectral data, of 1 A to 1.5 A for double spectral data, and of 0.6 A for triple spectral data sets. The quality of the assignments and 3D structures from the optimal data using all three spectra were similar to those obtained from traditional assignment methods with structural variations within the bundle of 0.6 A and 1.3 A for backbone and heavy atoms, respectively. Almost all constraints (97%) of the automatic NOESY cross peak assignments were cross compatible with the structures from the conventional manual assignment procedure, and an even larger proportion (99%) of the manually derived constraints were compatible with the automatically determined 3D structures. The two mean structures determined by both methods differed only by 1.3 A rmsd for the backbone atoms in the well-defined regions of the protein. Thus NOAD/DIAMOD analysis of spectra from labeled proteins provides a reliable method for high throughput analysis of genomic targets

Crystal Structures of SlyA Protein, a Master Virulence Regulator of Salmonella, in Free and DNA-bound States

Energy Technology Data Exchange (ETDEWEB)

Dolan, Kyle T.; Duguid, Erica M.; He, Chuan (UC)

2011-11-17

SlyA is a master virulence regulator that controls the transcription of numerous genes in Salmonella enterica. We present here crystal structures of SlyA by itself and bound to a high-affinity DNA operator sequence in the slyA gene. SlyA interacts with DNA through direct recognition of a guanine base by Arg-65, as well as interactions between conserved Arg-86 and the minor groove and a large network of non-base-specific contacts with the sugar phosphate backbone. Our structures, together with an unpublished structure of SlyA bound to the small molecule effector salicylate (Protein Data Bank code 3DEU), reveal that, unlike many other MarR family proteins, SlyA dissociates from DNA without large conformational changes when bound to this effector. We propose that SlyA and other MarR global regulators rely more on indirect readout of DNA sequence to exert control over many genes, in contrast to proteins (such as OhrR) that recognize a single operator.

Structural and dynamic characterization of eukaryotic gene regulatory protein domains in solution

Energy Technology Data Exchange (ETDEWEB)

Lee, Andrew Loyd [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

1996-05-01

Solution NMR was primarily used to characterize structure and dynamics in two different eukaryotic protein systems: the δ-Al-ε activation domain from c-jun and the Drosophila RNA-binding protein Sex-lethal. The second system is the Drosophila Sex-lethal (Sxl) protein, an RNA-binding protein which is the ``master switch`` in sex determination. Sxl contains two adjacent RNA-binding domains (RBDs) of the RNP consensus-type. The NMR spectrum of the second RBD (Sxl-RBD2) was assigned using multidimensional heteronuclear NMR, and an intermediate-resolution family of structures was calculated from primarily NOE distance restraints. The overall fold was determined to be similar to other RBDs: a βαβ-βαβ pattern of secondary structure, with the two helices packed against a 4-stranded anti-parallel β-sheet. In addition ¹⁵N T₁, T₂, and ¹⁵N/¹H NOE relaxation measurements were carried out to characterize the backbone dynamics of Sxl-RBD2 in solution. RNA corresponding to the polypyrimidine tract of transformer pre-mRNA was generated and titrated into 3 different Sxl-RBD protein constructs. Combining Sxl-RBD1+2 (bht RBDs) with this RNA formed a specific, high affinity protein/RNA complex that is amenable to further NMR characterization. The backbone ¹H, ¹³C, and ¹⁵N resonances of Sxl-RBD1+2 were assigned using a triple-resonance approach, and ¹⁵N relaxation experiments were carried out to characterize the backbone dynamics of this complex. The changes in chemical shift in Sxl-RBD1+2 upon binding RNA are observed using Sxl-RBD2 as a substitute for unbound Sxl-RBD1+2. This allowed the binding interface to be qualitatively mapped for the second domain.

Reliability-based optimization of engineering structures

DEFF Research Database (Denmark)

Sørensen, John Dalsgaard

2008-01-01

The theoretical basis for reliability-based structural optimization within the framework of Bayesian statistical decision theory is briefly described. Reliability-based cost benefit problems are formulated and exemplitied with structural optimization. The basic reliability-based optimization...... problems are generalized to the following extensions: interactive optimization, inspection and repair costs, systematic reconstruction, re-assessment of existing structures. Illustrative examples are presented including a simple introductory example, a decision problem related to bridge re...

Hierarchical Conformational Analysis of Native Lysozyme Based on Sub-Millisecond Molecular Dynamics Simulations.

Directory of Open Access Journals (Sweden)

Kai Wang

Full Text Available Hierarchical organization of free energy landscape (FEL for native globular proteins has been widely accepted by the biophysics community. However, FEL of native proteins is usually projected onto one or a few dimensions. Here we generated collectively 0.2 milli-second molecular dynamics simulation trajectories in explicit solvent for hen egg white lysozyme (HEWL, and carried out detailed conformational analysis based on backbone torsional degrees of freedom (DOF. Our results demonstrated that at micro-second and coarser temporal resolutions, FEL of HEWL exhibits hub-like topology with crystal structures occupying the dominant structural ensemble that serves as the hub of conformational transitions. However, at 100 ns and finer temporal resolutions, conformational substates of HEWL exhibit network-like topology, crystal structures are associated with kinetic traps that are important but not dominant ensembles. Backbone torsional state transitions on time scales ranging from nanoseconds to beyond microseconds were found to be associated with various types of molecular interactions. Even at nanoseconds temporal resolution, the number of conformational substates that are of statistical significance is quite limited. These observations suggest that detailed analysis of conformational substates at multiple temporal resolutions is both important and feasible. Transition state ensembles among various conformational substates at microsecond temporal resolution were observed to be considerably disordered. Life times of these transition state ensembles are found to be nearly independent of the time scales of the participating torsional DOFs.

Three-Dimensional Printed PCL-Based Implantable Prototypes of Medical Devices for Controlled Drug Delivery

DEFF Research Database (Denmark)

Hollander, Jenny; Genina, Natalja; Jukarainen, Harri

2016-01-01

The goal of the present study was to fabricate drug-containing T-shaped prototypes of intrauterine system (IUS) with the drug incorporated within the entire backbone of the medical device using 3-dimensional (3D) printing technique, based on fused deposition modeling (FDM™). Indomethacin was used...... prototypes were dependent on the amount of drug loading. The drug release profiles from the printed devices were faster than from the corresponding filaments due to a lower degree of the drug crystallinity in IUS in addition to the differences in the external/internal structure and geometry between...

Structural effects on the electronic characteristics of intramolecularly intercalated alkali-rubrene complexes

International Nuclear Information System (INIS)

Li, Tsung-Lung; Lu, Wen-Cai

2016-01-01

The geometric and electronic structures of neutral monolithium- and monosodium-rubrene (Li 1 Rub and Na 1 Rub) isomers are investigated and compared with monopotassium-rubrene (K 1 Rub). Based on the alkali binding site, all isomers of these alkali-rubrene complexes can be subdivided into two types: intramolecularly intercalated and extramolecularly adsorbed. The minimum-energy Li 1 Rub and Na 1 Rub are intercalated structures, whereas the minimum-energy K 1 Rub is adsorbed. The fact that the intercalated Li 1 Rub and Na 1 Rub structures are energetically favorable over the adsorbed ones can be explained by two energy rules. First, “double” proximity of the intercalating alkali element to a pair of phenyl side groups enormously reduces the total energy. Second, accommodation of a minuscule intercalant does not significantly deform the carbon frame and, thus, increases the energy only by a small amount. Additionally, the peculiar effects of intramolecular intercalation on the electronic structures of molecules are also studied in this simulation of monoalkali intercalation. In the monoalkali-intercalated rubrene complex, only one of the two pairs of phenyl groups of rubrene is intercalated, intentionally leaving another pair pristine, which facilitates the comparison of electronic structures between the intercalated and pristine pairs of phenyl side groups in a single molecule. The uniformity of chemical environments of the phenyl groups of the intercalated Li 1 Rub/Na 1 Rub is deteriorated by the incorporation of the intercalant, and leads to their spectral characteristics in contrast to K 1 Rub. In particular, the introduction of the intercalant promotes the carbon 2p orbitals of the intercalated phenyl pair to take part in the electronic structures of the HOMO and LUMO peaks of Li 1 Rub/Na 1 Rub. The unpaired electron in the HOMO is delocalized over the backbone with higher probability of distributing over the central two fused rings than over the outer two

Integrating ICT in Agriculture for Knowledge-Based Economy

African Journals Online (AJOL)

agriculture –based livelihoods, demands the integration of ICT knowledge with agriculture. .... (CGIAR) shows the vital role of Agricultural development in Rwanda's ... Network, Rwanda National Backbone Project, Regional Communication.

Side-chain tunability of furan-containing low-band-gap polymers provides control of structural order in efficient solar cells

KAUST Repository

Yiu, Alan T.; Beaujuge, Pierre; Lee, Olivia P.; Woo, Claire; Toney, Michael F.; Frechet, Jean

2012-01-01

The solution-processability of conjugated polymers in organic solvents has classically been achieved by modulating the size and branching of alkyl substituents appended to the backbone. However, these substituents impact structural order and charge transport properties in thin-film devices. As a result, a trade-off must be found between material solubility and insulating alkyl content. It was recently shown that the substitution of furan for thiophene in the backbone of the polymer PDPP2FT significantly improves polymer solubility, allowing for the use of shorter branched side chains while maintaining high device efficiency. In this report, we use PDPP2FT to demonstrate that linear alkyl side chains can be used to promote thin-film nanostructural order. In particular, linear side chains are shown to shorten π-π stacking distances between backbones and increase the correlation lengths of both π-π stacking and lamellar spacing, leading to a substantial increase in the efficiency of bulk heterojunction solar cells. © 2011 American Chemical Society.

Side-chain tunability of furan-containing low-band-gap polymers provides control of structural order in efficient solar cells

KAUST Repository

Yiu, Alan T.

2012-02-01

The solution-processability of conjugated polymers in organic solvents has classically been achieved by modulating the size and branching of alkyl substituents appended to the backbone. However, these substituents impact structural order and charge transport properties in thin-film devices. As a result, a trade-off must be found between material solubility and insulating alkyl content. It was recently shown that the substitution of furan for thiophene in the backbone of the polymer PDPP2FT significantly improves polymer solubility, allowing for the use of shorter branched side chains while maintaining high device efficiency. In this report, we use PDPP2FT to demonstrate that linear alkyl side chains can be used to promote thin-film nanostructural order. In particular, linear side chains are shown to shorten π-π stacking distances between backbones and increase the correlation lengths of both π-π stacking and lamellar spacing, leading to a substantial increase in the efficiency of bulk heterojunction solar cells. © 2011 American Chemical Society.

Synthesis and molecular characterization of chitosan based polyurethane elastomers using aromatic diisocyanate.

Science.gov (United States)

Zia, Khalid Mahmood; Anjum, Sohail; Zuber, Mohammad; Mujahid, Muhammad; Jamil, Tahir

2014-05-01

The present research work was performed to synthesize a new series of chitosan based polyurethane elastomers (PUEs) using poly(ɛ-caprolactone) (PCL). The chitosan based PUEs were prepared by step-growth polymerization technique using poly(ɛ-caprolactone) (PCL) and 2,4-toluene diisocyanate (TDI). In the second step the PU prepolymer was extended with different mole ratios of chitosan and 1,4-butane diol (BDO). Molecular engineering was carried out during the synthesis. The conventional spectroscopic characterization of the synthesized samples using FT-IR confirms the existence of the proposed chitosan based PUEs structure. Internal morphology of the prepared PUEs was studied using SEM analysis. The SEM images confirmed the incorporation of chitosan molecules into the PU backbone. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of NMR and crystal structures for the proteins TM1112 and TM1367

International Nuclear Information System (INIS)

Mohanty, Biswaranjan; Serrano, Pedro; Pedrini, Bill; Jaudzems, Kristaps; Geralt, Michael; Horst, Reto; Herrmann, Torsten; Elsliger, Marc-André; Wilson, Ian A.; Wüthrich, Kurt

2010-01-01

NMR structures of the proteins TM1112 and TM1367 solved by the JCSG in solution at 298 K could be superimposed with the corresponding crystal structures at 100 K with r.m.s.d. values of <1.0 Å for the backbone heavy atoms. For both proteins the structural differences between multiple molecules in the asymmetric unit of the crystals correlated with structural variations within the bundles of conformers used to represent the NMR solution structures. A recently introduced JCSG NMR structure-determination protocol, which makes use of the software package UNIO for extensive automation, was further evaluated by comparison of the TM1112 structure obtained using these automated methods with another NMR structure that was independently solved in another PSI center, where a largely interactive approach was applied. The NMR structures of the TM1112 and TM1367 proteins from Thermotoga maritima in solution at 298 K were determined following a new protocol which uses the software package UNIO for extensive automation. The results obtained with this novel procedure were evaluated by comparison with the crystal structures solved by the JCSG at 100 K to 1.83 and 1.90 Å resolution, respectively. In addition, the TM1112 solution structure was compared with an NMR structure solved by the NESG using a conventional largely interactive methodology. For both proteins, the newly determined NMR structure could be superimposed with the crystal structure with r.m.s.d. values of <1.0 Å for the backbone heavy atoms, which provided a starting platform to investigate local structure variations, which may arise from either the methods used or from the different chemical environments in solution and in the crystal. Thereby, these comparative studies were further explored with the use of reference NMR and crystal structures, which were computed using the NMR software with input of upper-limit distance constraints derived from the molecular models that represent the results of structure

Toward structural dynamics: protein motions viewed by chemical shift modulations and direct detection of C'N multiple-quantum relaxation.

Science.gov (United States)

Mori, Mirko; Kateb, Fatiha; Bodenhausen, Geoffrey; Piccioli, Mario; Abergel, Daniel

2010-03-17

Multiple quantum relaxation in proteins reveals unexpected relationships between correlated or anti-correlated conformational backbone dynamics in alpha-helices or beta-sheets. The contributions of conformational exchange to the relaxation rates of C'N coherences (i.e., double- and zero-quantum coherences involving backbone carbonyl (13)C' and neighboring amide (15)N nuclei) depend on the kinetics of slow exchange processes, as well as on the populations of the conformations and chemical shift differences of (13)C' and (15)N nuclei. The relaxation rates of C'N coherences, which reflect concerted fluctuations due to slow chemical shift modulations (CSMs), were determined by direct (13)C detection in diamagnetic and paramagnetic proteins. In well-folded proteins such as lanthanide-substituted calbindin (CaLnCb), copper,zinc superoxide dismutase (Cu,Zn SOD), and matrix metalloproteinase (MMP12), slow conformational exchange occurs along the entire backbone. Our observations demonstrate that relaxation rates of C'N coherences arising from slow backbone dynamics have positive signs (characteristic of correlated fluctuations) in beta-sheets and negative signs (characteristic of anti-correlated fluctuations) in alpha-helices. This extends the prospects of structure-dynamics relationships to slow time scales that are relevant for protein function and enzymatic activity.

IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico

Directory of Open Access Journals (Sweden)

Hong Jun-Jie

2009-05-01

Full Text Available Abstract Background Internal ribosomal entry sites (IRESs provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. Results We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. Conclusion IRSS is freely available at this website http://140.135.61.9/ires/. In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.

Band structure of comb-like photonic crystals containing meta-materials

Science.gov (United States)

Weng, Yi; Wang, Zhi-Guo; Chen, Hong

2007-09-01

We study the transmission properties and band structure of comb-like photonic crystals (PC) with backbones constructed of meta-materials (negative-index materials) within the frame of the interface response theory. The result shows the existence of a special band gap at low frequency. This gap differs from the Bragg gaps in that it is insensitive to the geometrical scaling and disorder. In comparison with the zero-average-index gap in one-dimensional PC made of alternating positive- and negative-index materials, the gap is obviously deeper and broader, given the same system parameters. In addition, the behavior of its gap-edges is also different. One gap-edge is decided by the average permittivity whereas the other is only subject to the changing of the permeability of the backbone. Due to this asymmetry of the two gap-edges, the broadening of the gap could be realized with much freedom and facility.

Mapping population-based structural connectomes.

Science.gov (United States)

Zhang, Zhengwu; Descoteaux, Maxime; Zhang, Jingwen; Girard, Gabriel; Chamberland, Maxime; Dunson, David; Srivastava, Anuj; Zhu, Hongtu

2018-05-15

Advances in understanding the structural connectomes of human brain require improved approaches for the construction, comparison and integration of high-dimensional whole-brain tractography data from a large number of individuals. This article develops a population-based structural connectome (PSC) mapping framework to address these challenges. PSC simultaneously characterizes a large number of white matter bundles within and across different subjects by registering different subjects' brains based on coarse cortical parcellations, compressing the bundles of each connection, and extracting novel connection weights. A robust tractography algorithm and streamline post-processing techniques, including dilation of gray matter regions, streamline cutting, and outlier streamline removal are applied to improve the robustness of the extracted structural connectomes. The developed PSC framework can be used to reproducibly extract binary networks, weighted networks and streamline-based brain connectomes. We apply the PSC to Human Connectome Project data to illustrate its application in characterizing normal variations and heritability of structural connectomes in healthy subjects. Copyright © 2018 Elsevier Inc. All rights reserved.

Thermoresponsive Poly(2-oxazoline) Molecular Brushes by Living Ionic Polymerization: Kinetic Investigations of Pendant Chain Grafting and Cloud Point Modulation by Backbone and Side Chain Length Variation

KAUST Repository

Zhang, Ning; Luxenhofer, Robert; Jordan, Rainer

2012-01-01

and the stretched conformation of the backbone, which is caused by the electrostatic repulsion of the oxazolinium moieties along the macroinitiator. The resulting molecular brushes showed thermoresponsive properties, that is, having a defined cloud point (CP

Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses

Science.gov (United States)

Wang, Jimin; Li, Yue; Modis, Yorgo

2014-01-01

The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1–E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain. PMID:24725935

Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain.

Science.gov (United States)

Nomura, Yusuke; Tanaka, Yoichiro; Fukunaga, Jun-ichi; Fujiwara, Kazuya; Chiba, Manabu; Iibuchi, Hiroaki; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Kozu, Tomoko; Sakamoto, Taiichi

2013-12-01

AML1/RUNX1 is an essential transcription factor involved in the differentiation of hematopoietic cells. AML1 binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. In a previous study, we obtained RNA aptamers against the AML1 Runt domain by systematic evolution of ligands by exponential enrichment and revealed that RNA aptamers exhibit higher affinity for the Runt domain than that for RDE and possess the 5'-GCGMGNN-3' and 5'-N'N'CCAC-3' conserved motif (M: A or C; N and N' form Watson-Crick base pairs) that is important for Runt domain binding. In this study, to understand the structural basis of recognition of the Runt domain by the aptamer motif, the solution structure of a 22-mer RNA was determined using nuclear magnetic resonance. The motif contains the AH(+)-C mismatch and base triple and adopts an unusual backbone structure. Structural analysis of the aptamer motif indicated that the aptamer binds to the Runt domain by mimicking the RDE sequence and structure. Our data should enhance the understanding of the structural basis of DNA mimicry by RNA molecules.

Modeling an in-register, parallel "iowa" aβ fibril structure using solid-state NMR data from labeled samples with rosetta.

Science.gov (United States)

Sgourakis, Nikolaos G; Yau, Wai-Ming; Qiang, Wei

2015-01-06

Determining the structures of amyloid fibrils is an important first step toward understanding the molecular basis of neurodegenerative diseases. For β-amyloid (Aβ) fibrils, conventional solid-state NMR structure determination using uniform labeling is limited by extensive peak overlap. We describe the characterization of a distinct structural polymorph of Aβ using solid-state NMR, transmission electron microscopy (TEM), and Rosetta model building. First, the overall fibril arrangement is established using mass-per-length measurements from TEM. Then, the fibril backbone arrangement, stacking registry, and "steric zipper" core interactions are determined using a number of solid-state NMR techniques on sparsely (13)C-labeled samples. Finally, we perform Rosetta structure calculations with an explicitly symmetric representation of the system. We demonstrate the power of the hybrid Rosetta/NMR approach by modeling the in-register, parallel "Iowa" mutant (D23N) at high resolution (1.2Å backbone rmsd). The final models are validated using an independent set of NMR experiments that confirm key features. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bending continuous structures with SMAs: a novel robotic fish design

International Nuclear Information System (INIS)

Rossi, C; Colorado, J; Coral, W; Barrientos, A

2011-01-01

In this paper, we describe our research on bio-inspired locomotion systems using deformable structures and smart materials, concretely shape memory alloys (SMAs). These types of materials allow us to explore the possibility of building motor-less and gear-less robots. A swimming underwater fish-like robot has been developed whose movements are generated using SMAs. These actuators are suitable for bending the continuous backbone of the fish, which in turn causes a change in the curvature of the body. This type of structural arrangement is inspired by fish red muscles, which are mainly recruited during steady swimming for the bending of a flexible but nearly incompressible structure such as the fishbone. This paper reviews the design process of these bio-inspired structures, from the motivations and physiological inspiration to the mechatronics design, control and simulations, leading to actual experimental trials and results. The focus of this work is to present the mechanisms by which standard swimming patterns can be reproduced with the proposed design. Moreover, the performance of the SMA-based actuators' control in terms of actuation speed and position accuracy is also addressed.

Bending continuous structures with SMAs: a novel robotic fish design.

Science.gov (United States)

Rossi, C; Colorado, J; Coral, W; Barrientos, A

2011-12-01

In this paper, we describe our research on bio-inspired locomotion systems using deformable structures and smart materials, concretely shape memory alloys (SMAs). These types of materials allow us to explore the possibility of building motor-less and gear-less robots. A swimming underwater fish-like robot has been developed whose movements are generated using SMAs. These actuators are suitable for bending the continuous backbone of the fish, which in turn causes a change in the curvature of the body. This type of structural arrangement is inspired by fish red muscles, which are mainly recruited during steady swimming for the bending of a flexible but nearly incompressible structure such as the fishbone. This paper reviews the design process of these bio-inspired structures, from the motivations and physiological inspiration to the mechatronics design, control and simulations, leading to actual experimental trials and results. The focus of this work is to present the mechanisms by which standard swimming patterns can be reproduced with the proposed design. Moreover, the performance of the SMA-based actuators' control in terms of actuation speed and position accuracy is also addressed.

Reliability-Based Optimization in Structural Engineering

DEFF Research Database (Denmark)

Enevoldsen, I.; Sørensen, John Dalsgaard

1994-01-01

In this paper reliability-based optimization problems in structural engineering are formulated on the basis of the classical decision theory. Several formulations are presented: Reliability-based optimal design of structural systems with component or systems reliability constraints, reliability...

Temperature-dependent spectral density analysis applied to monitoring backbone dynamics of major urinary protein-I complexed with the pheromone 2-sec-butyl-4,5-dihydrothiazole

International Nuclear Information System (INIS)

Krizova, Hana; Zidek, Lukas; Stone, Martin J.; Novotny, Milos V.; Sklenar, Vladimir

2004-01-01

Backbone dynamics of mouse major urinary protein I (MUP-I) was studied by 15 N NMR relaxation. Data were collected at multiple temperatures for a complex of MUP-I with its natural pheromonal ligand, 2-sec-4,5-dihydrothiazole, and for the free protein. The measured relaxation rates were analyzed using the reduced spectral density mapping. Graphical analysis of the spectral density values provided an unbiased qualitative picture of the internal motions. Varying temperature greatly increased the range of analyzed spectral density values and therefore improved reliability of the analysis. Quantitative parameters describing the dynamics on picosecond to nanosecond time scale were obtained using a novel method of simultaneous data fitting at multiple temperatures. Both methods showed that the backbone flexibility on the fast time scale is slightly increased upon pheromone binding, in accordance with the previously reported results. Zero-frequency spectral density values revealed conformational changes on the microsecond to millisecond time scale. Measurements at different temperatures allowed to monitor temperature depencence of the motional parameters

CASD-NMR 2: robust and accurate unsupervised analysis of raw NOESY spectra and protein structure determination with UNIO

International Nuclear Information System (INIS)

Guerry, Paul; Duong, Viet Dung; Herrmann, Torsten

2015-01-01

UNIO is a comprehensive software suite for protein NMR structure determination that enables full automation of all NMR data analysis steps involved—including signal identification in NMR spectra, sequence-specific backbone and side-chain resonance assignment, NOE assignment and structure calculation. Within the framework of the second round of the community-wide stringent blind NMR structure determination challenge (CASD-NMR 2), we participated in two categories of CASD-NMR 2, namely using either raw NMR spectra or unrefined NOE peak lists as input. A total of 15 resulting NMR structure bundles were submitted for 9 out of 10 blind protein targets. All submitted UNIO structures accurately coincided with the corresponding blind targets as documented by an average backbone root mean-square deviation to the reference proteins of only 1.2 Å. Also, the precision of the UNIO structure bundles was virtually identical to the ensemble of reference structures. By assessing the quality of all UNIO structures submitted to the two categories, we find throughout that only the UNIO–ATNOS/CANDID approach using raw NMR spectra consistently yielded structure bundles of high quality for direct deposition in the Protein Data Bank. In conclusion, the results obtained in CASD-NMR 2 are another vital proof for robust, accurate and unsupervised NMR data analysis by UNIO for real-world applications

Tunable Thermosetting Epoxies Based on Fractionated and Well-Characterized Lignins.

Science.gov (United States)

Gioia, Claudio; Lo Re, Giada; Lawoko, Martin; Berglund, Lars

2018-03-21

Here we report the synthesis of thermosetting resins from low molar mass Kraft lignin fractions of high functionality, refined by solvent extraction. Such fractions were fully characterized by 31 P NMR, 2D-HSQC NMR, SEC, and DSC in order to obtain a detailed description of the structures. Reactive oxirane moieties were introduced on the lignin backbone under mild reaction conditions and quantified by simple 1 H NMR analysis. The modified fractions were chemically cross-linked with a flexible polyether diamine ( M n ≈ 2000), in order to obtain epoxy thermosets. Epoxies from different lignin fractions, studied by DSC, DMA, tensile tests, and SEM, demonstrated substantial differences in terms of thermo-mechanical properties. For the first time, strong relationships between lignin structures and epoxy properties could be demonstrated. The suggested approach provides unprecedented possibilities to tune network structure and properties of thermosets based on real lignin fractions, rather than model compounds.

Structural deformation upon protein-protein interaction: a structural alphabet approach.

Science.gov (United States)

Martin, Juliette; Regad, Leslie; Lecornet, Hélène; Camproux, Anne-Claude

2008-02-28

In a number of protein-protein complexes, the 3D structures of bound and unbound partners significantly differ, supporting the induced fit hypothesis for protein-protein binding. In this study, we explore the induced fit modifications on a set of 124 proteins available in both bound and unbound forms, in terms of local structure. The local structure is described thanks to a structural alphabet of 27 structural letters that allows a detailed description of the backbone. Using a control set to distinguish induced fit from experimental error and natural protein flexibility, we show that the fraction of structural letters modified upon binding is significantly greater than in the control set (36% versus 28%). This proportion is even greater in the interface regions (41%). Interface regions preferentially involve coils. Our analysis further reveals that some structural letters in coil are not favored in the interface. We show that certain structural letters in coil are particularly subject to modifications at the interface, and that the severity of structural change also varies. These information are used to derive a structural letter substitution matrix that summarizes the local structural changes observed in our data set. We also illustrate the usefulness of our approach to identify common binding motifs in unrelated proteins. Our study provides qualitative information about induced fit. These results could be of help for flexible docking.

Structural deformation upon protein-protein interaction: A structural alphabet approach

Directory of Open Access Journals (Sweden)

Lecornet Hélène

2008-02-01

Full Text Available Abstract Background In a number of protein-protein complexes, the 3D structures of bound and unbound partners significantly differ, supporting the induced fit hypothesis for protein-protein binding. Results In this study, we explore the induced fit modifications on a set of 124 proteins available in both bound and unbound forms, in terms of local structure. The local structure is described thanks to a structural alphabet of 27 structural letters that allows a detailed description of the backbone. Using a control set to distinguish induced fit from experimental error and natural protein flexibility, we show that the fraction of structural letters modified upon binding is significantly greater than in the control set (36% versus 28%. This proportion is even greater in the interface regions (41%. Interface regions preferentially involve coils. Our analysis further reveals that some structural letters in coil are not favored in the interface. We show that certain structural letters in coil are particularly subject to modifications at the interface, and that the severity of structural change also varies. These information are used to derive a structural letter substitution matrix that summarizes the local structural changes observed in our data set. We also illustrate the usefulness of our approach to identify common binding motifs in unrelated proteins. Conclusion Our study provides qualitative information about induced fit. These results could be of help for flexible docking.

Structure based alignment and clustering of proteins (STRALCP)

Science.gov (United States)

Zemla, Adam T.; Zhou, Carol E.; Smith, Jason R.; Lam, Marisa W.

2013-06-18

Disclosed are computational methods of clustering a set of protein structures based on local and pair-wise global similarity values. Pair-wise local and global similarity values are generated based on pair-wise structural alignments for each protein in the set of protein structures. Initially, the protein structures are clustered based on pair-wise local similarity values. The protein structures are then clustered based on pair-wise global similarity values. For each given cluster both a representative structure and spans of conserved residues are identified. The representative protein structure is used to assign newly-solved protein structures to a group. The spans are used to characterize conservation and assign a "structural footprint" to the cluster.

Characterization of hydrogen bonding motifs in proteins: hydrogen elimination monitoring by ultraviolet photodissociation mass spectrometry.

Science.gov (United States)

Morrison, Lindsay J; Chai, Wenrui; Rosenberg, Jake A; Henkelman, Graeme; Brodbelt, Jennifer S

2017-08-02

Determination of structure and folding of certain classes of proteins remains intractable by conventional structural characterization strategies and has spurred the development of alternative methodologies. Mass spectrometry-based approaches have a unique capacity to differentiate protein heterogeneity due to the ability to discriminate populations, whether minor or major, featuring modifications or complexation with non-covalent ligands on the basis of m/z. Cleavage of the peptide backbone can be further utilized to obtain residue-specific structural information. Here, hydrogen elimination monitoring (HEM) upon ultraviolet photodissociation (UVPD) of proteins transferred to the gas phase via nativespray ionization is introduced as an innovative approach to deduce backbone hydrogen bonding patterns. Using well-characterized peptides and a series of proteins, prediction of the engagement of the amide carbonyl oxygen of the protein backbone in hydrogen bonding using UVPD-HEM is demonstrated to show significant agreement with the hydrogen-bonding motifs derived from molecular dynamics simulations and X-ray crystal structures.

Predicting beta-turns and their types using predicted backbone dihedral angles and secondary structures.

Science.gov (United States)

Kountouris, Petros; Hirst, Jonathan D

2010-07-31

Beta-turns are secondary structure elements usually classified as coil. Their prediction is important, because of their role in protein folding and their frequent occurrence in protein chains. We have developed a novel method that predicts beta-turns and their types using information from multiple sequence alignments, predicted secondary structures and, for the first time, predicted dihedral angles. Our method uses support vector machines, a supervised classification technique, and is trained and tested on three established datasets of 426, 547 and 823 protein chains. We achieve a Matthews correlation coefficient of up to 0.49, when predicting the location of beta-turns, the highest reported value to date. Moreover, the additional dihedral information improves the prediction of beta-turn types I, II, IV, VIII and "non-specific", achieving correlation coefficients up to 0.39, 0.33, 0.27, 0.14 and 0.38, respectively. Our results are more accurate than other methods. We have created an accurate predictor of beta-turns and their types. Our method, called DEBT, is available online at http://comp.chem.nottingham.ac.uk/debt/.

Credit networks and systemic risk of Chinese local financing platforms: Too central or too big to fail?. -based on different credit correlations using hierarchical methods

Science.gov (United States)

He, Fang; Chen, Xi

2016-11-01

The accelerating accumulation and risk concentration of Chinese local financing platforms debts have attracted wide attention throughout the world. Due to the network of financial exposures among institutions, the failure of several platforms or regions of systemic importance will probably trigger systemic risk and destabilize the financial system. However, the complex network of credit relationships in Chinese local financing platforms at the state level remains unknown. To fill this gap, we presented the first complex networks and hierarchical cluster analysis of the credit market of Chinese local financing platforms using the ;bottom up; method from firm-level data. Based on balance-sheet channel, we analyzed the topology and taxonomy by applying the analysis paradigm of subdominant ultra-metric space to an empirical data in 2013. It is remarked that we chose to extract the network of co-financed financing platforms in order to evaluate the effect of risk contagion from platforms to bank system. We used the new credit similarity measure by combining the factor of connectivity and size, to extract minimal spanning trees (MSTs) and hierarchical trees (HTs). We found that: (1) the degree distributions of credit correlation backbone structure of Chinese local financing platforms are fat tailed, and the structure is unstable with respect to targeted failures; (2) the backbone is highly hierarchical, and largely explained by the geographic region; (3) the credit correlation backbone structure based on connectivity and size is significantly heterogeneous; (4) key platforms and regions of systemic importance, and contagion path of systemic risk are obtained, which are contributed to preventing systemic risk and regional risk of Chinese local financing platforms and preserving financial stability under the framework of macro prudential supervision. Our approach of credit similarity measure provides a means of recognizing ;systemically important; institutions and regions

Chemical synthesis of membrane proteins by the removable backbone modification method.

Science.gov (United States)

Tang, Shan; Zuo, Chao; Huang, Dong-Liang; Cai, Xiao-Ying; Zhang, Long-Hua; Tian, Chang-Lin; Zheng, Ji-Shen; Liu, Lei

2017-12-01

Chemical synthesis can produce membrane proteins bearing specifically designed modifications (e.g., phosphorylation, isotope labeling) that are difficult to obtain through recombinant protein expression approaches. The resulting homogeneously modified synthetic membrane proteins are valuable tools for many advanced biochemical and biophysical studies. This protocol describes the chemical synthesis of membrane proteins by condensation of transmembrane peptide segments through native chemical ligation. To avoid common problems encountered due to the poor solubility of transmembrane peptides in almost any solvent, we describe an effective procedure for the chemical synthesis of membrane proteins through the removable-backbone modification (RBM) strategy. Two key steps of this protocol are: (i) installation of solubilizing Arg4-tagged RBM groups into the transmembrane peptides at any primary amino acid through Fmoc (9-fluorenylmethyloxycarbonyl) solid-phase peptide synthesis and (ii) native ligation of the full-length sequence, followed by removal of the RBM tags by TFA (trifluoroacetic acid) cocktails to afford the native protein. The installation of RBM groups is achieved by using 4-methoxy-5-nitrosalicyladehyde by reduction amination to incorporate an activated O-to-N acyl transfer auxiliary. The Arg4-tag-modified membrane-spanning peptide segments behave like water-soluble peptides to facilitate their purification, ligation and mass characterization.

Strontium Titanate-based Composite Anodes for Solid Oxide Fuel Cells

DEFF Research Database (Denmark)

Blennow Tullmar, Peter; Kammer Hansen, Kent; Wallenberg, L.R.

2008-01-01

Surfactant-assisted infiltration of Gd-doped ceria (CGO) in Nb-doped SrTiO3 (STN) was investigated as a potential fuel electrode for solid oxide fuel cells (SOFC). An electronically conductive backbone structure of STN was first fabricated at high temperatures and then combined with the mixed con...

Bulk Heterojunction Solar Cells: Impact of Minor Structural Modifications to the Polymer Backbone on the Polymer-Fullerene Mixing and Packing and on the Fullerene-Fullerene Connecting Network

KAUST Repository

Wang, Tonghui

2018-01-25

The morphology of the active layer of a bulk heterojunction solar cell, made of a blend of an electron-donating polymer and an electron-accepting fullerene derivative, is known to play a determining role in device performance. Here, a combination of molecular dynamics simulations and long-range corrected density functional theory calculations is used to elucidate the molecular-scale effects that even minor structural changes to the polymer backbone can have on the “local” morphology; this study focuses on the extent of polymer–fullerene mixing, on their packing, and on the characteristics of the fullerene–fullerene connecting network in the mixed regions, aspects that are difficult to access experimentally. Three representative polymer donors are investigated: (i) poly[(5,6-difluoro-2,1,3-benzothiadiazol-4,7-diyl)-alt-(3,3′″-di(2-octyldodecyl)-2,2′;5′,2″;5″,2′″-quaterthiophen-5,5′″-diyl)] (PffBT4T-2OD); (ii) poly[(2,1,3-benzothiadiazol-4,7-diyl)-alt-(3,3′″-di(2-octyldodecyl)-2,2′;5′,2″;5″,2′″-quaterthiophen-5,5′″-diyl)] (PBT4T-2OD), where the fluorine atoms in the benzothiadiazole moieties of PffBT4T-2OD are replaced with hydrogen atoms; and (iii) poly[(2,2′-bithiophene)-alt-(4,7-bis((2-decyltetradecyl)thiophen-2-yl)-5,6-difluoro-2-propyl-2H-benzo[d][1,2,3]triazole)] (PT2-FTAZ), where the sulfur atoms in the benzothiadiazole moieties of PffBT4T-2OD are replaced with nitrogen atoms carrying a linear C3H7 side-chain; these polymers are mixed with the phenyl-C71-butyric acid methyl ester (PC71BM) acceptor. This study also discusses the nature of the charge-transfer electronic states appearing at the donor–acceptor interfaces, the electronic couplings relevant for the charge-recombination process, and the electron-transfer features between neighboring PC71BM molecules.

Bulk Heterojunction Solar Cells: Impact of Minor Structural Modifications to the Polymer Backbone on the Polymer-Fullerene Mixing and Packing and on the Fullerene-Fullerene Connecting Network

KAUST Repository

Wang, Tonghui; Chen, Xiankai; Ashokan, Ajith; Zheng, Zilong; Ravva, Mahesh Kumar; Bré das, Jean-Luc

2018-01-01

The morphology of the active layer of a bulk heterojunction solar cell, made of a blend of an electron-donating polymer and an electron-accepting fullerene derivative, is known to play a determining role in device performance. Here, a combination of molecular dynamics simulations and long-range corrected density functional theory calculations is used to elucidate the molecular-scale effects that even minor structural changes to the polymer backbone can have on the “local” morphology; this study focuses on the extent of polymer–fullerene mixing, on their packing, and on the characteristics of the fullerene–fullerene connecting network in the mixed regions, aspects that are difficult to access experimentally. Three representative polymer donors are investigated: (i) poly[(5,6-difluoro-2,1,3-benzothiadiazol-4,7-diyl)-alt-(3,3′″-di(2-octyldodecyl)-2,2′;5′,2″;5″,2′″-quaterthiophen-5,5′″-diyl)] (PffBT4T-2OD); (ii) poly[(2,1,3-benzothiadiazol-4,7-diyl)-alt-(3,3′″-di(2-octyldodecyl)-2,2′;5′,2″;5″,2′″-quaterthiophen-5,5′″-diyl)] (PBT4T-2OD), where the fluorine atoms in the benzothiadiazole moieties of PffBT4T-2OD are replaced with hydrogen atoms; and (iii) poly[(2,2′-bithiophene)-alt-(4,7-bis((2-decyltetradecyl)thiophen-2-yl)-5,6-difluoro-2-propyl-2H-benzo[d][1,2,3]triazole)] (PT2-FTAZ), where the sulfur atoms in the benzothiadiazole moieties of PffBT4T-2OD are replaced with nitrogen atoms carrying a linear C3H7 side-chain; these polymers are mixed with the phenyl-C71-butyric acid methyl ester (PC71BM) acceptor. This study also discusses the nature of the charge-transfer electronic states appearing at the donor–acceptor interfaces, the electronic couplings relevant for the charge-recombination process, and the electron-transfer features between neighboring PC71BM molecules.

A Path Based Model for a Green Liner Shipping Network Design

DEFF Research Database (Denmark)

Brouer, Berit Dangaard; Jepsen, Mads Kehlet; Plum, Christian Edinger Munk

Liner shipping networks are the backbone of international trade providing low transportation cost, which is a major driver of globalization. These networks are under constant pressure to deliver capacity, cost eectiveness and environmentally conscious transport solutions. This article proposes...... a new path based MIP model for the Liner shipping Network Design Problem minimizing the cost of vessels and their fuel consumption facilitating a green network. The proposed model reduces problem size using a novel aggregation of demands. A decomposition method enabling delayed column generation...... is presented. The subproblems have similar structure to Vehicle Routing Problems, which can be solved using dynamic programming. An algorithm has been implemented for this model, unfortunately with discouraging results due to the structure of the subproblem and the lack of proper dominance criteria...

Phosphorus Binding Sites in Proteins: Structural Preorganization and Coordination

DEFF Research Database (Denmark)

Gruber, Mathias Felix; Greisen, Per Junior; Junker, Märta Caroline

2014-01-01

to individual structures that bind to phosphate groups; here, we investigate a total of 8307 structures obtained from the RCSB Protein Data Bank (PDB). An analysis of the binding site amino acid propensities reveals very characteristic first shell residue distributions, which are found to be influenced...... by the characteristics of the phosphorus compound and by the presence of cobound cations. The second shell, which supports the coordinating residues in the first shell, is found to consist mainly of protein backbone groups. Our results show how the second shell residue distribution is dictated mainly by the first shell...

MBE System for Antimonide Based Semiconductor Lasers

National Research Council Canada - National Science Library

Lester, Luke

1999-01-01

.... SLR-770 inductively coupled plasma (ICP) processing system. The SLR-770 has been invaluable in the study of plasma etching of AlGaAsSb and GaSb-materials that form the backbone of antimonide-based semiconductor lasers...

Thermodynamics and local structure of vinyl polymer melts

International Nuclear Information System (INIS)

Yethiraj, A.; Curro, J.G.; Rajasekaran, J.J.

1995-01-01

Monte Carlo simulation results are reported for the site-site pair correlations and equation of state of model vinyl polymer melts. The molecules are freely jointed hard chains with a hard sphere side-group attached to every other backbone bead. The local structure and pressure are investigated as a function of the diameter of the side group for melt-like densities. The intramolecular correlation functions are well represented by a single chain model where excluded volume interactions are included for beads separated by four bonds or less and neglected otherwise. The intermolecular correlation functions show interesting packing effects. The side group shields the backbone beads from approaching each other, to a degree that increases with increasing diameter of the side group. The polymer reference interaction site model integral equation theory is in good agreement with the simulation results for the pair correlation functions. At fixed volume fraction, the pressure is found to be a non-monotonic function of the size of the side group. copyright 1995 American Institute of Physics

Performance-based shape optimization of continuum structures

International Nuclear Information System (INIS)

Liang Qingquan

2010-01-01

This paper presents a performance-based optimization (PBO) method for optimal shape design of continuum structures with stiffness constraints. Performance-based design concepts are incorporated in the shape optimization theory to achieve optimal designs. In the PBO method, the traditional shape optimization problem of minimizing the weight of a continuum structure with displacement or mean compliance constraints is transformed to the problem of maximizing the performance of the structure. The optimal shape of a continuum structure is obtained by gradually eliminating inefficient finite elements from the structure until its performance is maximized. Performance indices are employed to monitor the performance of optimized shapes in an optimization process. Performance-based optimality criteria are incorporated in the PBO method to identify the optimum from the optimization process. The PBO method is used to produce optimal shapes of plane stress continuum structures and plates in bending. Benchmark numerical results are provided to demonstrate the effectiveness of the PBO method for generating the maximum stiffness shape design of continuum structures. It is shown that the PBO method developed overcomes the limitations of traditional shape optimization methods in optimal design of continuum structures. Performance-based optimality criteria presented can be incorporated in any shape and topology optimization methods to obtain optimal designs of continuum structures.

Plasma-based accelerator structures

International Nuclear Information System (INIS)

Schroeder, Carl B.

1999-01-01

Plasma-based accelerators have the ability to sustain extremely large accelerating gradients, with possible high-energy physics applications. This dissertation further develops the theory of plasma-based accelerators by addressing three topics: the performance of a hollow plasma channel as an accelerating structure, the generation of ultrashort electron bunches, and the propagation of laser pulses is underdense plasmas

Georesistivity structure in the central part of North-Eastern Japan Arc; Tohoku chiho chubu chiiki no denki dendodo kozo

Energy Technology Data Exchange (ETDEWEB)

Fujinawa, Y. [National Research Institute for Disaster Prevention, Tsukuba (Japan); Kawakami, N. [GERD Geothermal Energy Research and Development Co. Ltd., Tokyo (Japan); Ueshima, M. [The University of Tokyo, Tokyo (Japan). Earthquake Research Institute; Honkura, Y. [Tokyo Institute of Technology, Tokyo (Japan)

1998-03-13

MT measurement of transects was made in the central part of North-Eastern Japan Arc to clarify tectonics of subduction zones. 1-D, 2-D and 3-D resistivity structures are observed in surface layers, and zones shallower and deeper than a Conrad surface, respectively. A main structure direction is S-N or NNE-SSW. Ishinomaki-Chokai tectonic line and low- resistivity zones due to Quaternary volcanos (Naruko, Onikobe) exist in a backbone range region. Resistivity is 100{Omega}{center_dot}m or less by Bostick Inversion except Mesozoic and Palaeozoic layers in the southern Kitakami mountainous region, resulting in a good agreement with previous results in a north transect. Resistivity is several {Omega}{center_dot}m and depth is several km around Shinjo basin and in surface layers of Kitakami River region. The backbone range region shows complex resistivity structures because of volcanic activity and wide-area hot water activity. High-resistivity layers correspond to stable Mesozoic and Palaeozoic land layers. Seismic velocity increases in the low-resistivity zone. Earthquake generally occurs at the boundary between resistivity structures. 68 refs., 9 figs., 2 tabs.

Influence of the strength of the smectic order on the backbone anisotropy of side-chain liquid crystal polymers as revealed by SANS

Science.gov (United States)

Noirez, L.; Keller, P.; Cotton, J. P.

1992-06-01

It is proposed that the strength of the smectic order determines the backbone anisotropy of side-chain liquid crystal polymers. Here this strength increases with the length of the alkyl terminal group of the mesogens. Two liquid crystal polymethacrylates differing only by the mesogenic tails —OCH3 and —OC4H9 are considered. The backbone anisotropy of these polymers is measured by small angle neutron scattering (SANS) whereas the smectic order is evaluated from the intensity of the 001 Bragg peak. Il est proposé que la qualité de l'ordre smectique détermine l'anisotropie du squelette de polymères mésomorphes en peigne confinés dans les lamelles. Ici l'ordre smectique est augmenté en allongeant le groupe alkyl terminal des mésogènes. Nous étudions deux polyméthacrylates cristal liquide qui ne différent que par leurs groupes terminaux : —OCH3 et —OC4H9. L'anisotropie du squellete est mesurée par diffusion de neutrons aux petits angles tandis que l'ordre smectique est évalué à l'aide de l'intensité du pic de Bragg 001.

Lactobacillus rhamnosus accelerates zebrafish backbone calcification and gonadal differentiation through effects on the GnRH and IGF systems.

Directory of Open Access Journals (Sweden)

Matteo A Avella

Full Text Available Endogenous microbiota play essential roles in the host's immune system, physiology, reproduction and nutrient metabolism. We hypothesized that a continuous administration of an exogenous probiotic might also influence the host's development. Thus, we treated zebrafish from birth to sexual maturation (2-months treatment with Lactobacillus rhamnosus, a probiotic species intended for human use. We monitored for the presence of L. rhamnosus during the entire treatment. Zebrafish at 6 days post fertilization (dpf exhibited elevated gene expression levels for Insulin-like growth factors -I and -II, Peroxisome proliferator activated receptors -α and -β, VDR-α and RAR-γ when compared to untreated-10 days old zebrafish. Using a gonadotropin-releasing hormone 3 GFP transgenic zebrafish (GnRH3-GFP, higher GnRH3 expression was found at 6, 8 and 10 dpf upon L. rhamnosus treatment. The same larvae exhibited earlier backbone calcification and gonad maturation. Noteworthy in the gonad development was the presence of first testes differentiation at 3 weeks post fertilization in the treated zebrafish population -which normally occurs at 8 weeks- and a dramatic sex ratio modulation (93% females, 7% males in control vs. 55% females, 45% males in the treated group. We infer that administration of L. rhamnosus stimulated the IGF system, leading to a faster backbone calcification. Moreover we hypothesize a role for administration of L. rhamnosus on GnRH3 modulation during early larval development, which in turn affects gonadal development and sex differentiation. These findings suggest a significant role of the microbiota composition on the host organism development profile and open new perspectives in the study of probiotics usage and application.

Compare local pocket and global protein structure models by small structure patterns

KAUST Repository

Cui, Xuefeng

2015-09-09

Researchers proposed several criteria to assess the quality of predicted protein structures because it is one of the essential tasks in the Critical Assessment of Techniques for Protein Structure Prediction (CASP) competitions. Popular criteria include root mean squared deviation (RMSD), MaxSub score, TM-score, GDT-TS and GDT-HA scores. All these criteria require calculation of rigid transformations to superimpose the the predicted protein structure to the native protein structure. Yet, how to obtain the rigid transformations is unknown or with high time complexity, and, hence, heuristic algorithms were proposed. In this work, we carefully design various small structure patterns, including the ones specifically tuned for local pockets. Such structure patterns are biologically meaningful, and address the issue of relying on a sufficient number of backbone residue fragments for existing methods. We sample the rigid transformations from these small structure patterns; and the optimal superpositions yield by these small structures are refined and reported. As a result, among 11; 669 pairs of predicted and native local protein pocket models from the CASP10 dataset, the GDT-TS scores calculated by our method are significantly higher than those calculated by LGA. Moreover, our program is computationally much more efficient. Source codes and executables are publicly available at http://www.cbrc.kaust.edu.sa/prosta/

Solid State Structure of Poly(9,9-dinonylfluorene)

DEFF Research Database (Denmark)

Torkkeli, Mika; Galbrecht, Frank; Scherf, Ullrich

2015-01-01

We report on X-ray diffraction and grazing-incidence X-ray diffraction data of poly(9,9-dinonylfluorene) (PF9) in bulk, thin films and in the 1% methylcyclohexane gel. We denote the main crystalline phase as alpha phase and propose that the unit cell is monoclinic (a = 29.31 angstrom, b = 23.......1 angstrom, and c = 16.7 angstrom). Structural analogues to other 9,9-di-n-alkyl-substituted polyfluorenes are discussed in terms of unit cell parameters and backbone geometry....

Combined quantum-mechanics/molecular-mechanics dynamics simulation of A-DNA double strands irradiated by ultra-low-energy carbon ions

Energy Technology Data Exchange (ETDEWEB)

Ngaojampa, C.; Nimmanpipug, P. [Computer Simulation and Modeling Laboratory (CSML), Department of Chemistry and Center for Innovation Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Yu, L.D., E-mail: yuld@fnrf.science.cmu.ac.t [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Anuntalabhochai, S. [Molecular Biology Laboratory, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Lee, V.S., E-mail: vannajan@gmail.co [Computer Simulation and Modeling Laboratory (CSML), Department of Chemistry and Center for Innovation Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand)

2011-02-15

In order to promote understanding of the fundamentals of ultra-low-energy ion interaction with DNA, molecular dynamics simulations using combined quantum-mechanics/molecular-mechanics of poly-AT and poly-GC A-DNA double strands irradiated by <200 eV carbon ions were performed to investigate the molecular implications of mutation bias. The simulations were focused on the responses of the DNA backbones and nitrogenous bases to irradiation. Analyses of the root mean square displacements of the backbones and non-hydrogen atoms of base rings of the simulated DNA structure after irradiation revealed a potential preference of DNA double strand separation, dependent on the irradiating energy. The results show that for the backbones, the large difference in the displacement between poly-GC and poly-AT in the initial time period could be the reason for the backbone breakage; for the nitrogenous base pairs, A-T is 30% more sensitive or vulnerable to ion irradiation than G-C, demonstrating a preferential, instead of random, effect of irradiation-induced mutation.

Combined quantum-mechanics/molecular-mechanics dynamics simulation of A-DNA double strands irradiated by ultra-low-energy carbon ions

International Nuclear Information System (INIS)

Ngaojampa, C.; Nimmanpipug, P.; Yu, L.D.; Anuntalabhochai, S.; Lee, V.S.

2011-01-01

In order to promote understanding of the fundamentals of ultra-low-energy ion interaction with DNA, molecular dynamics simulations using combined quantum-mechanics/molecular-mechanics of poly-AT and poly-GC A-DNA double strands irradiated by <200 eV carbon ions were performed to investigate the molecular implications of mutation bias. The simulations were focused on the responses of the DNA backbones and nitrogenous bases to irradiation. Analyses of the root mean square displacements of the backbones and non-hydrogen atoms of base rings of the simulated DNA structure after irradiation revealed a potential preference of DNA double strand separation, dependent on the irradiating energy. The results show that for the backbones, the large difference in the displacement between poly-GC and poly-AT in the initial time period could be the reason for the backbone breakage; for the nitrogenous base pairs, A-T is 30% more sensitive or vulnerable to ion irradiation than G-C, demonstrating a preferential, instead of random, effect of irradiation-induced mutation.

Structure-based classification and ontology in chemistry

Directory of Open Access Journals (Sweden)

Hastings Janna

2012-04-01

Full Text Available Abstract Background Recent years have seen an explosion in the availability of data in the chemistry domain. With this information explosion, however, retrieving relevant results from the available information, and organising those results, become even harder problems. Computational processing is essential to filter and organise the available resources so as to better facilitate the work of scientists. Ontologies encode expert domain knowledge in a hierarchically organised machine-processable format. One such ontology for the chemical domain is ChEBI. ChEBI provides a classification of chemicals based on their structural features and a role or activity-based classification. An example of a structure-based class is 'pentacyclic compound' (compounds containing five-ring structures, while an example of a role-based class is 'analgesic', since many different chemicals can act as analgesics without sharing structural features. Structure-based classification in chemistry exploits elegant regularities and symmetries in the underlying chemical domain. As yet, there has been neither a systematic analysis of the types of structural classification in use in chemistry nor a comparison to the capabilities of available technologies. Results We analyze the different categories of structural classes in chemistry, presenting a list of patterns for features found in class definitions. We compare these patterns of class definition to tools which allow for automation of hierarchy construction within cheminformatics and within logic-based ontology technology, going into detail in the latter case with respect to the expressive capabilities of the Web Ontology Language and recent extensions for modelling structured objects. Finally we discuss the relationships and interactions between cheminformatics approaches and logic-based approaches. Conclusion Systems that perform intelligent reasoning tasks on chemistry data require a diverse set of underlying computational

Resolution of deep nodes yields an improved backbone phylogeny and a new basal lineage to study early evolution of Asteraceae.

Science.gov (United States)

Panero, Jose L; Freire, Susana E; Ariza Espinar, Luis; Crozier, Bonnie S; Barboza, Gloria E; Cantero, Juan J

2014-11-01

A backbone phylogeny that fully resolves all subfamily and deeper nodes of Asteraceae was constructed using 14 chloroplast DNA loci. The recently named genus Famatinanthus was found to be sister to the Mutisioideae-Asteroideae clade that represents more than 99% of Asteraceae and was found to have the two chloroplast inversions present in all Asteraceae except the nine genera of Barnadesioideae. A monotypic subfamily Famatinanthoideae and tribe Famatinantheae are named herein as new. Relationships among the basal lineages of the family were resolved with strong support in the Bayesian analysis as (Barnadesioideae (Famatinanthoideae (Mutisioideae (Stifftioideae (Wunderlichioideae-Asteroideae))))). Ancestral state reconstruction of ten morphological characters at the root node of the Asteraceae showed that the ancestral sunflower would have had a woody habit, alternate leaves, solitary capitulescences, epaleate receptacles, smooth styles, smooth to microechinate pollen surface sculpturing, white to yellow corollas, and insect-mediated pollination. Herbaceous habit, echinate pollen surface, pubescent styles, and cymose capitulescences were reconstructed for backbone nodes of the phylogeny corresponding to clades that evolved shortly after Asteraceae dispersed out of South America. No support was found for discoid capitula, multiseriate involucres or bird pollination as the ancestral character condition for any node. Using this more resolved phylogenetic tree, the recently described Raiguenrayun cura+Mutisiapollis telleriae fossil should be associated to a more derived node than previously suggested when time calibrating phylogenies of Asteraceae. Copyright © 2014 Elsevier Inc. All rights reserved.

Flexibility-based damage detection for in-service highway bridge

Science.gov (United States)

Dahal, Sushil; Jang, Shinae; Mensah-Bonsu, Priscilla

2012-04-01

Highway bridges are the backbones of a country's road network infrastructure. In order to efficiently maintain these important structures, structural health monitoring (SHM) can be implemented to impart a more deterministic management procedure. To date, many damage detection strategies have been developed and implemented on lab-scale or simple bridge structures however, damage detection research has rarely been conducted taking full scale in-service structures into account with ambient vibration. Among the different approaches modal flexibility method is one of the sensitive tools for damage detection which has been widely used over the last two decades. This paper presents a damage detection based on the stochastic damage locating vector (SDLV) method for an in-service highway bridge using ambient vibration data from long-term SHM. The target bridge was equipped with a long-term SHM system as a part of a research project of the University of Connecticut. The ambient vibration data during 2001 and 2005 are used to identify the damage on the highway bridge. Finally, the potential damage locations are determined using the SDLV method with the limited number of sensors.

Uncovering the essential links in online commercial networks

Science.gov (United States)

Zeng, Wei; Fang, Meiling; Shao, Junming; Shang, Mingsheng

2016-09-01

Recommender systems are designed to effectively support individuals' decision-making process on various web sites. It can be naturally represented by a user-object bipartite network, where a link indicates that a user has collected an object. Recently, research on the information backbone has attracted researchers' interests, which is a sub-network with fewer nodes and links but carrying most of the relevant information. With the backbone, a system can generate satisfactory recommenda- tions while saving much computing resource. In this paper, we propose an enhanced topology-aware method to extract the information backbone in the bipartite network mainly based on the information of neighboring users and objects. Our backbone extraction method enables the recommender systems achieve more than 90% of the accuracy of the top-L recommendation, however, consuming only 20% links. The experimental results show that our method outperforms the alternative backbone extraction methods. Moreover, the structure of the information backbone is studied in detail. Finally, we highlight that the information backbone is one of the most important properties of the bipartite network, with which one can significantly improve the efficiency of the recommender system.

A data base for aging of structural materials

International Nuclear Information System (INIS)

Oland, C.B.; Naus, D.J.; Jerath, S.

1993-01-01

USNRC initiated a Structural Aging (SAG) Program ORNL. The objective of the program is to provide assistance in identifying potential structural safety issues and to establish acceptance criteria for use in nuclear power plant evaluations for continued service. One main part focuses on the development of a Structural Materials Information Center where long-term and environment-dependent material properties are being collected and assembled into a data base. This data base is presented in two complementary formats. The Structural Materials Handbook is an expandable, hard-copy reference document that contains the complete data base for each material. The Structural Materials Electronic Data Base is accessible using an IBM-compatible personal computer. This paper presents an overview of the Structural Materials Information Center and briefly describes the features of the handbook and the electronic data base. In addition, a proposed method for using the data base to establish current property values for materials in existing concrete structures and to estimate the future performance of these materials is also presented

On the relationship between residue structural environment and sequence conservation in proteins.

Science.gov (United States)

Liu, Jen-Wei; Lin, Jau-Ji; Cheng, Chih-Wen; Lin, Yu-Feng; Hwang, Jenn-Kang; Huang, Tsun-Tsao

2017-09-01

Residues that are crucial to protein function or structure are usually evolutionarily conserved. To identify the important residues in protein, sequence conservation is estimated, and current methods rely upon the unbiased collection of homologous sequences. Surprisingly, our previous studies have shown that the sequence conservation is closely correlated with the weighted contact number (WCN), a measure of packing density for residue's structural environment, calculated only based on the C α positions of a protein structure. Moreover, studies have shown that sequence conservation is correlated with environment-related structural properties calculated based on different protein substructures, such as a protein's all atoms, backbone atoms, side-chain atoms, or side-chain centroid. To know whether the C α atomic positions are adequate to show the relationship between residue environment and sequence conservation or not, here we compared C α atoms with other substructures in their contributions to the sequence conservation. Our results show that C α positions are substantially equivalent to the other substructures in calculations of various measures of residue environment. As a result, the overlapping contributions between C α atoms and the other substructures are high, yielding similar structure-conservation relationship. Take the WCN as an example, the average overlapping contribution to sequence conservation is 87% between C α and all-atom substructures. These results indicate that only C α atoms of a protein structure could reflect sequence conservation at the residue level. © 2017 Wiley Periodicals, Inc.

Structural Ordering of Semiconducting Polymers and Small-Molecules for Organic Electronics

Science.gov (United States)

O'Hara, Kathryn Allison

Semiconducting polymers and small-molecules can be readily incorporated into electronic devices such as organic photovoltaics (OPVs), thermoelectrics (OTEs), organic light emitting diodes (OLEDs), and organic thin film transistors (OTFTs). Organic materials offer the advantage of being processable from solution to form flexible and lightweight thin films. The molecular design, processing, and resulting thin film morphology of semiconducting polymers drastically affect the optical and electronic properties. Charge transport within films of semiconducting polymers relies on the nanoscale organization to ensure electronic coupling through overlap of molecular orbitals and to provide continuous transport pathways. While the angstrom-scale packing details can be studied using X-ray scattering methods, an understanding of the mesoscale, or the length scale over which smaller ordered regions connect, is much harder to achieve. Grain boundaries play an important role in semiconducting polymer thin films where the average grain size is much smaller than the total distance which charges must traverse in order to reach the electrodes in a device. The majority of semiconducting polymers adopt a lamellar packing structure in which the conjugated backbones align in parallel pi-stacks separated by the alkyl side-chains. Only two directions of transport are possible--along the conjugated backbone and in the pi-stacking direction. Currently, the discussion of transport between crystallites is centered around the idea of tie-chains, or "bridging" polymer chains connecting two ordered regions. However, as molecular structures become increasingly complex with the development of new donor-acceptor copolymers, additional forms of connectivity between ordered domains should be considered. High resolution transmission electron microscopy (HRTEM) is a powerful tool for directly imaging the crystalline grain boundaries in polymer and small-molecule thin films. Recently, structures

Structural basis for Marburg virus VP35-mediated immune evasion mechanisms

Energy Technology Data Exchange (ETDEWEB)

Ramanan, Parameshwaran; Edwards, Megan R.; Shabman, Reed S.; Leung, Daisy W.; Endlich-Frazier, Ariel C.; Borek, Dominika M.; Otwinowski, Zbyszek; Liu, Gai; Huh, Juyoung; Basler, Christopher F.; Amarasinghe, Gaya K. [Sinai; (WU-MED); (UTSMC)

2013-07-22

Filoviruses, marburgvirus (MARV) and ebolavirus (EBOV), are causative agents of highly lethal hemorrhagic fever in humans. MARV and EBOV share a common genome organization but show important differences in replication complex formation, cell entry, host tropism, transcriptional regulation, and immune evasion. Multifunctional filoviral viral protein (VP) 35 proteins inhibit innate immune responses. Recent studies suggest double-stranded (ds)RNA sequestration is a potential mechanism that allows EBOV VP35 to antagonize retinoic-acid inducible gene-I (RIG-I) like receptors (RLRs) that are activated by viral pathogen–associated molecular patterns (PAMPs), such as double-strandedness and dsRNA blunt ends. Here, we show that MARV VP35 can inhibit IFN production at multiple steps in the signaling pathways downstream of RLRs. The crystal structure of MARV VP35 IID in complex with 18-bp dsRNA reveals that despite the similar protein fold as EBOV VP35 IID, MARV VP35 IID interacts with the dsRNA backbone and not with blunt ends. Functional studies show that MARV VP35 can inhibit dsRNA-dependent RLR activation and interferon (IFN) regulatory factor 3 (IRF3) phosphorylation by IFN kinases TRAF family member-associated NFkb activator (TANK) binding kinase-1 (TBK-1) and IFN kB kinase e (IKKe) in cell-based studies. We also show that MARV VP35 can only inhibit RIG-I and melanoma differentiation associated gene 5 (MDA5) activation by double strandedness of RNA PAMPs (coating backbone) but is unable to inhibit activation of RLRs by dsRNA blunt ends (end capping). In contrast, EBOV VP35 can inhibit activation by both PAMPs. Insights on differential PAMP recognition and inhibition of IFN induction by a similar filoviral VP35 fold, as shown here, reveal the structural and functional plasticity of a highly conserved virulence factor.

Backbone modified TBA analogues endowed with antiproliferative activity.

Science.gov (United States)

Esposito, Veronica; Russo, Annapina; Amato, Teresa; Varra, Michela; Vellecco, Valentina; Bucci, Mariarosaria; Russo, Giulia; Virgilio, Antonella; Galeone, Aldo

2017-05-01

The thrombin binding aptamer (TBA) is endowed with antiproliferative properties but its potential development is counteracted by the concomitant anticoagulant activity. Five oligonucleotides (ODNs) based on TBA sequence (GGTTGGTGTGGTTGG) and containing l-residues or both l-residues and inversion of polarity sites have been investigated by NMR and CD techniques for their ability to form G-quadruplex structures. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay), and their resistance in fetal bovine serum have been tested. CD and NMR data suggest that the investigated ODNs are able to form right- and left-handed G-quadruplex structures. All ODNs do not retain the anticoagulant activity characteristic of TBA but are endowed with a significant antiproliferative activity against two cancerous cell lines. Their resistance in biological environment after six days is variable, depending on the ODN. A comparison between results and literature data suggests that the antiproliferative activity of the TBA analogues investigated could depends on two factors: a) biological pathways and targets different from those already identified or proposed for other antiproliferative G-quadruplex aptamers, and b) the contribution of the guanine-based degradation products. Modified TBA analogues containing l-residues and inversion of polarity sites lose the anticoagulant activity but gain antiproliferative properties against two cancer cell lines. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016 Elsevier B.V. All rights reserved.

An Algebro-Topological Description of Protein Domain Structure

Science.gov (United States)

Penner, Robert Clark; Knudsen, Michael; Wiuf, Carsten; Andersen, Jørgen Ellegaard

2011-01-01

The space of possible protein structures appears vast and continuous, and the relationship between primary, secondary and tertiary structure levels is complex. Protein structure comparison and classification is therefore a difficult but important task since structure is a determinant for molecular interaction and function. We introduce a novel mathematical abstraction based on geometric topology to describe protein domain structure. Using the locations of the backbone atoms and the hydrogen bonds, we build a combinatorial object – a so-called fatgraph. The description is discrete yet gives rise to a 2-dimensional mathematical surface. Thus, each protein domain corresponds to a particular mathematical surface with characteristic topological invariants, such as the genus (number of holes) and the number of boundary components. Both invariants are global fatgraph features reflecting the interconnectivity of the domain by hydrogen bonds. We introduce the notion of robust variables, that is variables that are robust towards minor changes in the structure/fatgraph, and show that the genus and the number of boundary components are robust. Further, we invesigate the distribution of different fatgraph variables and show how only four variables are capable of distinguishing different folds. We use local (secondary) and global (tertiary) fatgraph features to describe domain structures and illustrate that they are useful for classification of domains in CATH. In addition, we combine our method with two other methods thereby using primary, secondary, and tertiary structure information, and show that we can identify a large percentage of new and unclassified structures in CATH. PMID:21629687

Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein.

Science.gov (United States)

Massiah, M A; Starich, M R; Paschall, C; Summers, M F; Christensen, A M; Sundquist, W I

1994-11-25

The HIV-1 matrix protein forms an icosahedral shell associated with the inner membrane of the mature virus. Genetic analyses have indicated that the protein performs important functions throughout the viral life-cycle, including anchoring the transmembrane envelope protein on the surface of the virus, assisting in viral penetration, transporting the proviral integration complex across the nuclear envelope, and localizing the assembling virion to the cell membrane. We now report the three-dimensional structure of recombinant HIV-1 matrix protein, determined at high resolution by nuclear magnetic resonance (NMR) methods. The HIV-1 matrix protein is the first retroviral matrix protein to be characterized structurally and only the fourth HIV-1 protein of known structure. NMR signal assignments required recently developed triple-resonance (1H, 13C, 15N) NMR methodologies because signals for 91% of 132 assigned H alpha protons and 74% of the 129 assignable backbone amide protons resonate within chemical shift ranges of 0.8 p.p.m. and 1 p.p.m., respectively. A total of 636 nuclear Overhauser effect-derived distance restraints were employed for distance geometry-based structure calculations, affording an average of 13.0 NMR-derived distance restraints per residue for the experimentally constrained amino acids. An ensemble of 25 refined distance geometry structures with penalties (sum of the squares of the distance violations) of 0.32 A2 or less and individual distance violations under 0.06 A was generated; best-fit superposition of ordered backbone heavy atoms relative to mean atom positions afforded root-mean-square deviations of 0.50 (+/- 0.08) A. The folded HIV-1 matrix protein structure is composed of five alpha-helices, a short 3(10) helical stretch, and a three-strand mixed beta-sheet. Helices I to III and the 3(10) helix pack about a central helix (IV) to form a compact globular domain that is capped by the beta-sheet. The C-terminal helix (helix V) projects away

Structural effects on the electronic characteristics of intramolecularly intercalated alkali-rubrene complexes

Energy Technology Data Exchange (ETDEWEB)

Li, Tsung-Lung, E-mail: quantum@mail.ncyu.edu.tw [Department of Electrophysics, National Chia-Yi University, 300 Hsueh-Fu Road, Chiayi, 60004, Taiwan, ROC (China); Lu, Wen-Cai, E-mail: wencailu@jlu.edu.cn [Laboratory of Fiber Materials and Modern Textile, Growing Base for State Key Laboratory, College of Physics, Qingdao University, Qingdao, Shandong 266071 (China); State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun, Jilin 130021 (China)

2016-11-01

The geometric and electronic structures of neutral monolithium- and monosodium-rubrene (Li{sub 1} Rub and Na{sub 1} Rub) isomers are investigated and compared with monopotassium-rubrene (K{sub 1} Rub). Based on the alkali binding site, all isomers of these alkali-rubrene complexes can be subdivided into two types: intramolecularly intercalated and extramolecularly adsorbed. The minimum-energy Li{sub 1} Rub and Na{sub 1} Rub are intercalated structures, whereas the minimum-energy K{sub 1} Rub is adsorbed. The fact that the intercalated Li{sub 1} Rub and Na{sub 1} Rub structures are energetically favorable over the adsorbed ones can be explained by two energy rules. First, “double” proximity of the intercalating alkali element to a pair of phenyl side groups enormously reduces the total energy. Second, accommodation of a minuscule intercalant does not significantly deform the carbon frame and, thus, increases the energy only by a small amount. Additionally, the peculiar effects of intramolecular intercalation on the electronic structures of molecules are also studied in this simulation of monoalkali intercalation. In the monoalkali-intercalated rubrene complex, only one of the two pairs of phenyl groups of rubrene is intercalated, intentionally leaving another pair pristine, which facilitates the comparison of electronic structures between the intercalated and pristine pairs of phenyl side groups in a single molecule. The uniformity of chemical environments of the phenyl groups of the intercalated Li{sub 1} Rub/Na{sub 1} Rub is deteriorated by the incorporation of the intercalant, and leads to their spectral characteristics in contrast to K{sub 1} Rub. In particular, the introduction of the intercalant promotes the carbon 2p orbitals of the intercalated phenyl pair to take part in the electronic structures of the HOMO and LUMO peaks of Li{sub 1} Rub/Na{sub 1} Rub. The unpaired electron in the HOMO is delocalized over the backbone with higher probability of

Energies and 2 '-Hydroxyl Group Orientations of RNA Backbone Conformations. Benchmark CCSD(T)/CBS Database, Electronic Analysis, and Assessment of DFT Methods and MD Simulations

Czech Academy of Sciences Publication Activity Database

Mládek, Arnošt; Banáš, P.; Jurečka, P.; Otyepka, M.; Zgarbová, M.; Šponer, Jiří

2014-01-01

Roč. 10, č. 1 (2014), s. 463-480 ISSN 1549-9618 R&D Projects: GA ČR(CZ) GAP208/12/1878; GA MŠk(CZ) ED1.1.00/02.0068 Institutional support: RVO:68081707 Keywords : DENSITY-FUNCTIONAL THEORY * SUGAR-PHOSPHATE BACKBONE * QUANTUM-CHEMICAL CALCULATIONS Subject RIV: BO - Biophysics Impact factor: 5.498, year: 2014

Production of structured lipids: acyl migration during enzymatic interesterification and downstream processing

DEFF Research Database (Denmark)

Xu, Xuebing

1997-01-01

Production of structured lipids by lipase-catalyzed interesterification attracts great interests recently. Structured lipids are defined, in this article, as triacylglycerols which contain both medium or short chain fatty acids and long chain fatty acids, each groups locating specifically in the sn......-2 position or sn-1,3 positions of glycerol backbone. These kinds of lipids are reported to be promising for both enteral and parenteral nutrition. However, acyl migration occurs in the reaction stage and downstream purification process. This side-reaction causes by-products which are harmful...

CtBP1/BARS Gly172 → Glu mutant structure: Impairing NAD(H)-binding and dimerization

International Nuclear Information System (INIS)

Nardini, Marco; Valente, Carmen; Ricagno, Stefano; Luini, Alberto; Corda, Daniela; Bolognesi, Martino

2009-01-01

C-terminal binding proteins (CtBPs) are multi-functional proteins involved in nuclear transcriptional co-repression, Golgi membrane fission, and synaptic ribbon formation. Binding of NAD(H) to CtBPs promotes dimerization. CtBP dimers act as a scaffold for multimeric protein complex formation, thus bridging transcriptional repressors and their targets in the nucleus. Based on size-exclusion chromatography experiments and on the crystal structure of the NAD(H)-free G172E CtBP mutant, we show here that absence of NAD(H) induces flexibility/backbone conformational changes at the dimerization interface and at the CtBP interdomain region. The results presented shed first light on the correlation between NAD(H)-binding and functional CtBP dimerization.

[Structure of crambin in solution, crystal and in the trajectories of molecular dynamics simulations].

Science.gov (United States)

Abaturov, L V; Nosova, N G

2013-01-01

The mechanisms of the three-dimensional crambin structure alterations in the crystalline environments and in the trajectories of the molecular dynamics simulations in the vacuum and crystal surroundings have been analyzed. In the crystalline state and in the solution the partial regrouping of remote intramolecular packing contacts, involved in the formation and stabilization of the tertiary structure of the crambin molecule, occurs in NMR structures. In the crystalline state it is initiated by the formation of the intermolecular contacts, the conformational influence of its appearance is distributed over the structure. The changes of the conformations and positions of the residues of the loop segments, where the intermolecular contacts of the crystal surroundings are preferably concentrated, are most observable. Under the influence of these contacts the principal change of the regular secondary structure of crambin is taking place: extension of the two-strand beta structure to the three-strand structure with the participation of the single last residue N46 of the C-terminal loop. In comparison with the C-terminal loop the more profound changes are observed in the conformation and the atomic positions of the backbone atoms and in the solvent accessibility of the residues of the interhelical loop. In the solution of the ensemble of the 8 NMR structures relative accessibility to the solvent differs more noticeably also in the region of the loop segments and rather markedly in the interhelical loop. In the crambin cryogenic crystal structures the positions of the atoms of the backbone and/or side chain of 14-18 of 46 residues are discretely disordered. The disorganizations of at least 8 of 14 residues occur directly in the regions of the intermolecular contacts and another 5 residues are disordered indirectly through the intramolecular contacts with the residues of the intermolecular contacts. Upon the molecular dynamics simulation in the vacuum surrounding as in the

Ensemble-based prediction of RNA secondary structures.

Science.gov (United States)

Aghaeepour, Nima; Hoos, Holger H

2013-04-24

Accurate structure prediction methods play an important role for the understanding of RNA function. Energy-based, pseudoknot-free secondary structure prediction is one of the most widely used and versatile approaches, and improved methods for this task have received much attention over the past five years. Despite the impressive progress that as been achieved in this area, existing evaluations of the prediction accuracy achieved by various algorithms do not provide a comprehensive, statistically sound assessment. Furthermore, while there is increasing evidence that no prediction algorithm consistently outperforms all others, no work has been done to exploit the complementary strengths of multiple approaches. In this work, we present two contributions to the area of RNA secondary structure prediction. Firstly, we use state-of-the-art, resampling-based statistical methods together with a previously published and increasingly widely used dataset of high-quality RNA structures to conduct a comprehensive evaluation of existing RNA secondary structure prediction procedures. The results from this evaluation clarify the performance relationship between ten well-known existing energy-based pseudoknot-free RNA secondary structure prediction methods and clearly demonstrate the progress that has been achieved in recent years. Secondly, we introduce AveRNA, a generic and powerful method for combining a set of existing secondary structure prediction procedures into an ensemble-based method that achieves significantly higher prediction accuracies than obtained from any of its component procedures. Our new, ensemble-based method, AveRNA, improves the state of the art for energy-based, pseudoknot-free RNA secondary structure prediction by exploiting the complementary strengths of multiple existing prediction procedures, as demonstrated using a state-of-the-art statistical resampling approach. In addition, AveRNA allows an intuitive and effective control of the trade-off between

Protein structure modeling for CASP10 by multiple layers of global optimization.