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Sample records for conformational stability structural

  1. Conformational stability of calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, C.S.; Trandum, C.; Larsen, N.

    2005-01-01

    The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (T-m) increased from 31 degrees C at pH 5 to 51 degrees C at pH 9, but electrophoretic analysis revealed that calreticulin oligomerized instead of unfolding. Structural analyses showed that the single C......-terminal a-helix was of major importance to the conformational stability of calreticulin....

  2. Conformational Stability, Structural Parameters And Vibrational Assignments of Allantoin

    International Nuclear Information System (INIS)

    Haman, S.

    2008-01-01

    Allantoin 2,5-Dioxo-4-imidazolinyl) urea , the diureide of glyoxylic acid, is a crystallisable oxidation product of uric acid found in allantoic and amniotic fluids, in fetal urine and in many plants. It is a healing, moisturizing, soothing and anti-irritating, keratolytic and non-toxic agent useful in dermatological, cosmetic and veterinary preparation. The optimized geometries and energies of the low-energy conformers of allantoin have been calculated using density functional theory (Daft) method. The calculations were performed with Beck's nonlocal three-parameter hybrid functional in combination with the Lee, Yang, and Parr correlation functional (By-play) using the 6-311++G(d,p) basis set. We calculated the infrared frequencies and intensities of the most stable conformers in order to assist in the assignment of the vibrational bands in the experimental spectrum. The B3LYP/6-311+G(d,p) harmonic force constants were scaled by applying the scaled quantum mechanical force field (SQM) technique. The calculated vibrational spectra were interpreted and band assignments were reported

  3. Microwave, infrared and Raman spectra, adjusted r{sub 0} structural parameters, conformational stability, and vibrational assignment of cyclopropylfluorosilane

    Energy Technology Data Exchange (ETDEWEB)

    Panikar, Savitha S. [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Guirgis, Gamil A.; Eddens, Matthew T.; Dukes, Horace W. [Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC 29424 (United States); Conrad, Andrew R.; Tubergen, Michael J. [Department of Chemistry, Kent State University, Kent, OH 44242 (United States); Gounev, Todor K. [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Durig, James R., E-mail: durigj@umkc.edu [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110 (United States)

    2013-03-29

    Highlights: ► The most stable gauche conformer has been identified from microwave spectra. ► Enthalpy difference has been determined between the two forms. ► Adjusted r{sub 0} structures were obtained for the gauche form. ► Ab initio calculations were performed for the two conformers. - Abstract: FT-microwave, infrared spectra of gas and Raman spectra of liquid for cyclopropylfluorosilane, c-C{sub 3}H{sub 5}SiH{sub 2}F have been recorded. 51 transitions for the {sup 28}Si, {sup 29}Si, and {sup 30}Si isotopomers have been assigned for the gauche conformer. Enthalpy differences in xenon solution by variable temperature infrared spectra between the more stable gauche and lesser stable cis form gave 109 ± 9 cm{sup −1}. From the microwave rotational constants for the three isotopomers ({sup 28}Si, {sup 29}Si, {sup 30}Si) combined with structural parameters predicted from MP2(full)/6-311+G(d, p) calculations, adjusted r{sub 0} structural parameters were obtained for the gauche conformer. The heavy atom distances (Å): Si–C{sub 2} = 1.836(3); C{sub 2}–C{sub 4} = 1.525(3); C{sub 2}–C{sub 5} = 1.519(3); C{sub 4}–C{sub 5} = 1.494(3); Si–F = 1.594(3) and angles (°): ∠CSiF = 111.2(5); ∠SiC{sub 2}C{sub 4} = 117.5(5); ∠SiC{sub 2}C{sub 5} = 119.2(5). To support the vibrational assignments, MP2(full)/6-31G(d) calculations were carried out. Results are discussed and compared to the corresponding properties of some similar molecules.

  4. Heat, Acid and Chemically Induced Unfolding Pathways, Conformational Stability and Structure-Function Relationship in Wheat α-Amylase.

    Directory of Open Access Journals (Sweden)

    Kritika Singh

    Full Text Available Wheat α-amylase, a multi-domain protein with immense industrial applications, belongs to α+β class of proteins with native molecular mass of 32 kDa. In the present study, the pathways leading to denaturation and the relevant unfolded states of this multi-domain, robust enzyme from wheat were discerned under the influence of temperature, pH and chemical denaturants. The structural and functional aspects along with thermodynamic parameters for α-amylase unfolding were probed and analyzed using fluorescence, circular dichroism and enzyme assay methods. The enzyme exhibited remarkable stability up to 70°C with tendency to aggregate at higher temperature. Acid induced unfolding was also incomplete with respect to the structural content of the enzyme. Strong ANS binding at pH 2.0 suggested the existence of a partially unfolded intermediate state. The enzyme was structurally and functionally stable in the pH range 4.0-9.0 with 88% recovery of hydrolytic activity. Careful examination of biophysical properties of intermediate states populated in urea and GdHCl induced denaturation suggests that α-amylase unfolding undergoes irreversible and non-coincidental cooperative transitions, as opposed to previous reports of two-state unfolding. Our investigation highlights several structural features of the enzyme in relation to its catalytic activity. Since, α-amylase has been comprehensively exploited for use in a range of starch-based industries, in addition to its physiological significance in plants and animals, knowledge regarding its stability and folding aspects will promote its biotechnological applications.

  5. Islands of conformational stability for filopodia.

    Directory of Open Access Journals (Sweden)

    D Robert Daniels

    Full Text Available Filopodia are long, thin protrusions formed when bundles of fibers grow outwardly from a cell surface while remaining closed in a membrane tube. We study the subtle issue of the mechanical stability of such filopodia and how this depends on the deformation of the membrane that arises when the fiber bundle adopts a helical configuration. We calculate the ground state conformation of such filopodia, taking into account the steric interaction between the membrane and the enclosed semiflexible fiber bundle. For typical filopodia we find that a minimum number of fibers is required for filopodium stability. Our calculation elucidates how experimentally observed filopodia can obviate the classical Euler buckling condition and remain stable up to several tens of μm. We briefly discuss how experimental observation of the results obtained in this work for the helical-like deformations of enclosing membrane tubes in filopodia could possibly be observed in the acrosomal reactions of the sea cucumber Thyone, and the horseshoe crab Limulus. Any realistic future theories for filopodium stability are likely to rely on an accurate treatment of such steric effects, as analysed in this work.

  6. Spectroscopic properties and conformational stability of Concholepas concholepas hemocyanin.

    Science.gov (United States)

    Idakieva, Krassimira; Nikolov, Peter; Chakarska, Irena; Genov, Nicolay; Shnyrov, Valery L

    2008-01-01

    The structure in solution and conformational stability of the hemocyanin from the Chilean gastropod mollusk Concholepas concholepas (CCH) and its structural subunits, CCH-A and CCH-B, were studied using fluorescence spectroscopy and differential scanning calorimetry (DSC). The fluorescence properties of the oxygenated and apo-form (copper-deprived) of the didecamer and its subunits were characterized. Besides tryptophan residues buried in the hydrophobic interior of the protein molecule also exposed fluorophores determine the fluorescence emission of the oxy- and apo-forms of the investigated hemocyanins. The copper-dioxygen system at the binuclear active site quenches the tryptophan emission of the oxy-forms of CCH and its subunits. The removal of this system increases the fluorescence quantum yield and causes structural rearrangement of the microenvironment of the emitting tryptophan residues in the respective apo-forms. Time-resolved fluorescence measurements show that the oxygenated and copper-deprived forms of the CCH and its subunits exist in different conformations. The thermal denaturation of the hemocyanin is an irreversible process, under kinetic control. A successive annealing procedure was applied to obtain the experimental deconvolution of the irreversible thermal transitions. Arrhenius equation parameter for the two-state irreversible model of the thermal denaturation of oxy-CCH at pH 7.2 was estimated. Both factors, oligomerization and the copper-dioxygen system at the active site, are important for stabilizing the structure of the hemocyanin molecule.

  7. Multiresolution Computation of Conformal Structures of Surfaces

    Directory of Open Access Journals (Sweden)

    Xianfeng Gu

    2003-10-01

    Full Text Available An efficient multiresolution method to compute global conformal structures of nonzero genus triangle meshes is introduced. The homology, cohomology groups of meshes are computed explicitly, then a basis of harmonic one forms and a basis of holomorphic one forms are constructed. A progressive mesh is generated to represent the original surface at different resolutions. The conformal structure is computed for the coarse level first, then used as the estimation for that of the finer level, by using conjugate gradient method it can be refined to the conformal structure of the finer level.

  8. Conformational stability and self-association equilibrium in biologics.

    Science.gov (United States)

    Clarkson, Benjamin R; Schön, Arne; Freire, Ernesto

    2016-02-01

    Biologics exist in equilibrium between native, partially denatured, and denatured conformational states. The population of any of these states is dictated by their Gibbs energy and can be altered by changes in physical and solution conditions. Some conformations have a tendency to self-associate and aggregate, an undesirable phenomenon in protein therapeutics. Conformational equilibrium and self-association are linked thermodynamic functions. Given that any associative reaction is concentration dependent, conformational stability studies performed at different protein concentrations can provide early clues to future aggregation problems. This analysis can be applied to the selection of protein variants or the identification of better formulation solutions. In this review, we discuss three different aggregation situations and their manifestation in the observed conformational equilibrium of a protein. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Thermal-induced conformational changes in the product release area drive the enzymatic activity of xylanases 10B: Crystal structure, conformational stability and functional characterization of the xylanase 10B from Thermotoga petrophila RKU-1

    International Nuclear Information System (INIS)

    Santos, Camila Ramos; Meza, Andreia Navarro; Hoffmam, Zaira Bruna; Silva, Junio Cota; Alvarez, Thabata Maria; Ruller, Roberto; Giesel, Guilherme Menegon; Verli, Hugo; Squina, Fabio Marcio; Prade, Rolf Alexander; Murakami, Mario Tyago

    2010-01-01

    Research highlights: → The hyperthermostable xylanase 10B from Thermotoga petrophila RKU-1 produces exclusively xylobiose at the optimum temperature. → Circular dichroism spectroscopy suggests a coupling effect of temperature-induced structural changes with its enzymatic behavior. → Crystallographic and molecular dynamics studies indicate that conformational changes in the product release area modulate the enzyme action mode. -- Abstract: Endo-xylanases play a key role in the depolymerization of xylan and recently, they have attracted much attention owing to their potential applications on biofuels and paper industries. In this work, we have investigated the molecular basis for the action mode of xylanases 10B at high temperatures using biochemical, biophysical and crystallographic methods. The crystal structure of xylanase 10B from hyperthermophilic bacterium Thermotoga petrophila RKU-1 (TpXyl10B) has been solved in the native state and in complex with xylobiose. The complex crystal structure showed a classical binding mode shared among other xylanases, which encompasses the -1 and -2 subsites. Interestingly, TpXyl10B displayed a temperature-dependent action mode producing xylobiose and xylotriose at 20 o C, and exclusively xylobiose at 90 o C as assessed by capillary zone electrophoresis. Moreover, circular dichroism spectroscopy suggested a coupling effect of temperature-induced structural changes with this particular enzymatic behavior. Molecular dynamics simulations supported the CD analysis suggesting that an open conformational state adopted by the catalytic loop (Trp297-Lys326) provokes significant modifications in the product release area (+1,+2 and +3 subsites), which drives the enzymatic activity to the specific release of xylobiose at high temperatures.

  10. Thermal-induced conformational changes in the product release area drive the enzymatic activity of xylanases 10B: Crystal structure, conformational stability and functional characterization of the xylanase 10B from Thermotoga petrophila RKU-1

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Camila Ramos; Meza, Andreia Navarro [Laboratorio Nacional de Biociencias (LNBio), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil); Hoffmam, Zaira Bruna; Silva, Junio Cota; Alvarez, Thabata Maria; Ruller, Roberto [Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil); Giesel, Guilherme Menegon; Verli, Hugo [Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Squina, Fabio Marcio [Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil); Prade, Rolf Alexander [Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, OK (United States); Murakami, Mario Tyago, E-mail: mario.murakami@lnbio.org.br [Laboratorio Nacional de Biociencias (LNBio), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil)

    2010-12-10

    Research highlights: {yields} The hyperthermostable xylanase 10B from Thermotoga petrophila RKU-1 produces exclusively xylobiose at the optimum temperature. {yields} Circular dichroism spectroscopy suggests a coupling effect of temperature-induced structural changes with its enzymatic behavior. {yields} Crystallographic and molecular dynamics studies indicate that conformational changes in the product release area modulate the enzyme action mode. -- Abstract: Endo-xylanases play a key role in the depolymerization of xylan and recently, they have attracted much attention owing to their potential applications on biofuels and paper industries. In this work, we have investigated the molecular basis for the action mode of xylanases 10B at high temperatures using biochemical, biophysical and crystallographic methods. The crystal structure of xylanase 10B from hyperthermophilic bacterium Thermotoga petrophila RKU-1 (TpXyl10B) has been solved in the native state and in complex with xylobiose. The complex crystal structure showed a classical binding mode shared among other xylanases, which encompasses the -1 and -2 subsites. Interestingly, TpXyl10B displayed a temperature-dependent action mode producing xylobiose and xylotriose at 20 {sup o}C, and exclusively xylobiose at 90 {sup o}C as assessed by capillary zone electrophoresis. Moreover, circular dichroism spectroscopy suggested a coupling effect of temperature-induced structural changes with this particular enzymatic behavior. Molecular dynamics simulations supported the CD analysis suggesting that an open conformational state adopted by the catalytic loop (Trp297-Lys326) provokes significant modifications in the product release area (+1,+2 and +3 subsites), which drives the enzymatic activity to the specific release of xylobiose at high temperatures.

  11. Sampling Realistic Protein Conformations Using Local Structural Bias

    DEFF Research Database (Denmark)

    Hamelryck, Thomas Wim; Kent, John T.; Krogh, A.

    2006-01-01

    The prediction of protein structure from sequence remains a major unsolved problem in biology. The most successful protein structure prediction methods make use of a divide-and-conquer strategy to attack the problem: a conformational sampling method generates plausible candidate structures, which...... are subsequently accepted or rejected using an energy function. Conceptually, this often corresponds to separating local structural bias from the long-range interactions that stabilize the compact, native state. However, sampling protein conformations that are compatible with the local structural bias encoded...... in a given protein sequence is a long-standing open problem, especially in continuous space. We describe an elegant and mathematically rigorous method to do this, and show that it readily generates native-like protein conformations simply by enforcing compactness. Our results have far-reaching implications...

  12. Insulin structure and stability.

    Science.gov (United States)

    Brange, J; Langkjoer, L

    1993-01-01

    Insulin is composed of 51 amino acids in two peptide chains (A and B) linked by two disulfide bonds. The three-dimensional structure of the insulin molecule (insulin monomer), essentially the same in solution and in solid phase, exists in two main conformations. These differ in the extent of helix in the B chain which is governed by the presence of phenol or its derivatives. In acid and neutral solutions, in concentrations relevant for pharmaceutical formulation, the insulin monomer assembles to dimers and at neutral pH, in the presence of zinc ions, further to hexamers. Many crystalline modifications of insulin have been identified but only those with the hexamer as the basic unit are utilized in preparations for therapy. The insulin hexamer forms a relatively stable unit but some flexibility remains within the individual molecules. The intrinsic flexibility at the ends of the B chain plays an important role in governing the physical and chemical stability of insulin. A variety of chemical changes of the primary structure (yielding insulin derivatives), and physical modifications of the secondary to quaternary structures (resulting in "denaturation," aggregation, and precipitation) are known to affect insulin and insulin preparations during storage and use (Fig. 8). The tendency of insulin to undergo structural transformation resulting in aggregation and formation of insoluble insulin fibrils has been one of the most intriguing and widely studied phenomena in relation to insulin stability. Although the exact mechanism of fibril formation is still obscure, it is now clear that the initial step is an exposure of certain hydrophobic residues, normally buried in the three-dimensional structure, to the surface of the insulin monomer. This requires displacement of the COOH-terminal B-chain residues from their normal position which can only be accomplished via monomerization of the insulin. Therefore, most methods stabilizing insulin against fibrillation share the

  13. Stability of generic thin shells in conformally flat spacetimes

    Energy Technology Data Exchange (ETDEWEB)

    Amirabi, Z. [Eastern Mediterranean Univ., Gazimagusa (Turkey). Dept. of Physics

    2017-07-15

    Some important spacetimes are conformally flat; examples are the Robertson-Walker cosmological metric, the Einstein-de Sitter spacetime, and the Levi-Civita-Bertotti-Robinson and Mannheim metrics. In this paper we construct generic thin shells in conformally flat spacetime supported by a perfect fluid with a linear equation of state, i.e., p = ωσ. It is shown that, for the physical domain of ω, i.e., 0 < ω ≤ 1, such thin shells are not dynamically stable. The stability of the timelike thin shells with the Mannheim spacetime as the outer region is also investigated. (orig.)

  14. Conformational impact of structural modifications in 2-fluorocyclohexanone

    Directory of Open Access Journals (Sweden)

    Francisco A. Martins

    2017-08-01

    Full Text Available 2-Haloketones are building blocks that combine physical, chemical and biological features of materials and bioactive compounds, while organic fluorine plays a fundamental role in the design of performance organic molecules. Since these features are dependent on the three-dimensional chemical structure of a molecule, simple structural modifications can affect its conformational stability and, consequently, the corresponding physicochemical/biological property of interest. In this work, structural changes in 2-fluorocyclohexanone were theoretically studied with the aim at finding intramolecular interactions that induce the conformational equilibrium towards the axial or equatorial conformer. The interactions evaluated were hydrogen bonding, hyperconjugation, electrostatic and steric effects. While the gauche effect, originated from hyperconjugative interactions, does not appear to cause some preferences for the axial conformation of organofluorine heterocycles, more classical effects indeed rule the conformational equilibrium of the compounds. Spectroscopic parameters (NMR chemical shifts and coupling constants, which can be useful to determine the stereochemistry and the interactions operating in the series of 2-fluorocyclohexanone derivatives, were also calculated.

  15. Conformation and stability of intramolecular telomeric G-quadruplexes: sequence effects in the loops.

    Directory of Open Access Journals (Sweden)

    Giovanna Sattin

    Full Text Available Telomeres are guanine-rich sequences that protect the ends of chromosomes. These regions can fold into G-quadruplex structures and their stabilization by G-quadruplex ligands has been employed as an anticancer strategy. Genetic analysis in human telomeres revealed extensive allelic variation restricted to loop bases, indicating that the variant telomeric sequences maintain the ability to fold into G-quadruplex. To assess the effect of mutations in loop bases on G-quadruplex folding and stability, we performed a comprehensive analysis of mutant telomeric sequences by spectroscopic techniques, molecular dynamics simulations and gel electrophoresis. We found that when the first position in the loop was mutated from T to C or A the resulting structure adopted a less stable antiparallel topology; when the second position was mutated to C or A, lower thermal stability and no evident conformational change were observed; in contrast, substitution of the third position from A to C induced a more stable and original hybrid conformation, while mutation to T did not significantly affect G-quadruplex topology and stability. Our results indicate that allelic variations generate G-quadruplex telomeric structures with variable conformation and stability. This aspect needs to be taken into account when designing new potential anticancer molecules.

  16. Importance of asparagine on the conformational stability and chemical reactivity of selected anti-inflammatory peptides

    Energy Technology Data Exchange (ETDEWEB)

    Soriano-Correa, Catalina, E-mail: csorico@comunidad.unam.mx [Química Computacional, Facultad de Estudios Superiores (FES)-Zaragoza, Universidad Nacional Autónoma de México (UNAM), Iztapalapa, C.P. 09230 México, D.F. (Mexico); Barrientos-Salcedo, Carolina [Laboratorio de Química Médica y Quimiogenómica, Facultad de Bioanálisis Campus Veracruz-Boca del Río, Universidad Veracruzana, C.P. 91700 Veracruz (Mexico); Campos-Fernández, Linda; Alvarado-Salazar, Andres [Química Computacional, Facultad de Estudios Superiores (FES)-Zaragoza, Universidad Nacional Autónoma de México (UNAM), Iztapalapa, C.P. 09230 México, D.F. (Mexico); Esquivel, Rodolfo O. [Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa (UAM-Iztapalapa), C.P. 09340 México, D.F. (Mexico)

    2015-08-18

    Highlights: • Asparagine plays an important role to anti-inflammatory effect of peptides. • The electron-donor substituent groups favor the formation of the hydrogen bonds, which contribute in the structural stability of peptides. • Chemical reactivity and the physicochemical features are crucial in the biological functions of peptides. - Abstract: Inflammatory response events are initiated by a complex series of molecular reactions that generate chemical intermediaries. The structure and properties of peptides and proteins are determined by the charge distribution of their side chains, which play an essential role in its electronic structure and physicochemical properties, hence on its biological functionality. The aim of this study was to analyze the effect of changing one central amino acid, such as substituting asparagine for aspartic acid, from Cys–Asn–Ser in aqueous solution, by assessing the conformational stability, physicochemical properties, chemical reactivity and their relationship with anti-inflammatory activity; employing quantum-chemical descriptors at the M06-2X/6-311+G(d,p) level. Our results suggest that asparagine plays a more critical role than aspartic acid in the structural stability, physicochemical features, and chemical reactivity of these tripeptides. Substituent groups in the side chain cause significant changes on the conformational stability and chemical reactivity, and consequently on their anti-inflammatory activity.

  17. Theoretical study on the adsorption and relative stability of conformers of L-ascorbic acid on γ - alumina (100) surface

    Science.gov (United States)

    Mozaffari Majd, M.; Dabbagh, H. A.; Farrokhpour, H.; Najafi Chermahini, A.

    2017-11-01

    The adsorption energies (Eads) and relative stabilities of selected conformers of the most stable tautomer of L-ascorbic acid (vitamin C) on the dehydroxylated γ-alumina (100) surface were calculated in both gas phase and solvent (water) using the density functional theory (DFT) method. The selected conformers were related to the different rotational angles of OH groups of L-ascorbic acid. The conformational analysis of bare tautomer in both gas and water showed that the conformer No.20 (conf. 20) and 13 (conf. 13) with the dihedral angles of H15sbnd O10sbnd C11sbnd C9 (-73°) and H20sbnd O19sbnd C9sbnd C11 (-135°) were the most stable and unstable conformers, respectively. The performed calculations in the presence of surface showed that the interaction of the conformers with the surface changes their relative stabilities and structures in both gas phase and water. The Ead of each conformer was calculated and it was determined that conf. 8 and conf. 16 have the highest value of Ead in the gas phase (-62.56 kcal/mol) and water (-54.44 kcal/mol), respectively. The optimized structure of each conformer on the surface and the number of hydrogen bonds between it and surface along with their bond lengths were determined.

  18. Influence of Tableting on the Conformation and Thermal Stability of Trypsin as a Model Protein

    DEFF Research Database (Denmark)

    Klukkert, Marten; Van De Weert, Marco; Fanø, Mathias

    2015-01-01

    was performed to determine the Tm as well as the folding reversibility after thermal denaturation of the reconstituted samples. It was found that compacted samples showed reduced activity accompanied by an altered secondary structure. Conformational changes that occur in the solid state were partially...... reversible upon tablet reconstitution. Aqueous-state IR spectroscopy combined with partial least squares was shown to be a powerful tool to follow irreversible structural changes and evaluate sample bioactivity. Besides its conformation, the thermal stability of trypsin was altered as a result of the applied...... compaction pressure, indicated by a reduced folding reversibility. In conclusion, this study reveals that tableting can have a negative impact on the biological quality of protein APIs....

  19. Conformal transformation and symplectic structure of self-dual fields

    International Nuclear Information System (INIS)

    Yang Kongqing; Luo Yan

    1996-01-01

    Considered two dimensional self-dual fields, the symplectic structure on the space of solutions is given. It is shown that this structure is Poincare invariant. The Lagrangian of two dimensional self-dual field is invariant under infinite one component conformal group, then this symplectic structure is also invariant under this conformal group. The conserved currents in geometrical formalism are also obtained

  20. Effects of modified β-cyclodextrin on thermal stability and conformation of lysozyme

    International Nuclear Information System (INIS)

    Kamiyama, Tadashi; Satoh, Megumi; Tateishi, Takahiro; Nojiri, Tomoaki; Takeuchi, Daisuke; Kimura, Takayoshi

    2012-01-01

    Highlights: ► Effects of cyclodextrin on stability and conformation of lysozyme were clarified. ► The CD influences the hydrophobic interaction of lysozyme by the inclusion. ► The CD relatively destabilized the folded state by stabilizing the unfolded state. ► The destabilization depends on the concentration and the substituent of CD. ► The conformation of lysozyme was more spread at unfolded state by inclusion of CD. - Abstract: Effects of cyclic oligosaccharide cyclodextrin (CD) on stability and conformation of lysozyme were clarified thermodynamically and rheologically by DSC, viscosity, and circular dichroism measurements. The modified β-CD relatively destabilized the folded state of lysozyme by stabilizing the unfolded state due to inclusion of hydrophobic part into the hydrophobic interior of CD. The order of higher destabilization effect was acetyl-β-CD > methyl-β-CD > hydroxypropyl-β-CD. Apparent number of bound CD to unfolded state for methyl-, hydroxypropyl-, and acetyl-β-CD is 6.7 ± 0.7, 4.2 ± 1.1, and 18.6 ± 4.3 and the binding constant is 5.5 ± 0.8, 6.7 ± 2.4, and 4.4 ± 1.2 L mol −1 , respectively. The viscosity for unfolded state was increased with an increase in the each modified β-CD concentration, suggesting that the inclusion of CD on a part of hydrophobic core at unfolded state leads to break the hydrophobic core, then lysozyme would be more spread structure. The substituent of CD can accelerate instability by directly breaking hydrogen bond and/or can restrain instability by increase in hydrophobic interaction. The fact that the each modified CDs has different destabilization effect shows a possibility to control the stability of protein by the substitution of CD.

  1. Conformational Structure of Tyrosine, Tyrosyl-Glycine, and Tyrosyl-Glycyl-Glycine by Double Resonance Spectroscopy

    Science.gov (United States)

    Abo-Riziq, Ali; Grace, Louis; Crews, Bridgit; Callahan, Michael P,; van Mourik, Tanja; de Vries, Mattanjah S,

    2011-01-01

    We investigated the variation in conformation for the amino acid tyrosine (Y), alone and in the small peptides tyrosine-glycine (YC) and tyrosine-glycine-glycine (YGG), in the gas phase by using UV-UV and IR-UV double resonance spectroscopy and density functional theory calculations. For tyrosine we found seven different conformations, for YG we found four different conformations, and for YGG we found three different conformations. As the peptides get larger, we observe fewer stable conformers, despite the increasing complexity and number of degrees of freedom. We find structural trends similar to those in phenylalanine-glycine glycine (FGG) and tryptophan-glycine-glycine (WGG)j however) the effect of dispersive forces in FGG for stabilizing a folded structure is replaced by that of hydrogen bonding in YGG.

  2. Spectra and structure of silicon containing compounds. XXXII. Raman and infrared spectra, conformational stability, vibrational assignment and ab initio calculations of n-propylsilane-d0 and Si-d3.

    Science.gov (United States)

    Durig, James R; Pan, Chunhua; Guirgis, Gamil A

    2003-03-15

    The infrared (3100-40 cm(-1)) and Raman (3100-20 cm(-1)) spectra of gaseous and solid n-propylsilane, CH(3)CH(2)CH(2)SiH(3) and the Si-d(3) isotopomer, CH(3)CH(2)CH(2)SiD(3), have been recorded. Additionally, the Raman spectra of the liquids have been recorded and qualitative depolarization values obtained. Both the anti and gauche conformers have been identified in the fluid phases but only the anti conformer remains in the solid. Variable temperature (-105 to -150 degrees C) studies of the infrared spectra of n-propylsilane dissolved in liquid krypton have been recorded and the enthalpy difference has been determined to be 220+/-22 cm(-1) (2.63+/-0.26 kJ mol(-1)) with the anti conformer the more stable form. A similar value of 234+/-23 cm(-1) (2.80+/-0.28 kJ mol(-1)) was obtained for deltaH for the Si-d(3) isotopomer. At ambient temperature it is estimated that there is 30+/-2% of the gauche conformer present. The potential function governing the conformation interchange has been estimated from the far infrared spectral data, the enthalpy difference, and the dihedral angle of the gauche conformer, which is compared to the one predicted from ab initio MP2/6-31G(d) calculations. The barriers to conformational interchange are: 942, 970 and 716 cm(-1) for the anti to gauche, gauche to gauche, and gauche to anti conformers, respectively. Relatively complete vibrational assignments are proposed for both the n-propylsilane-d(0) and Si-d(3) molecules based on the relative infrared and Raman spectral intensities, infrared band contours, depolarization ratios, and normal coordinate calculations. The geometrical parameters, harmonic force constants, vibrational frequencies, infrared intensities, Raman activities and depolarization ratios, and energy differences have been obtained for the anti and gauche conformers from ab initio MP2/6-31G(d) calculations. Structural parameters and energy differences have also been obtained utilizing the larger 6-311 + G(d,p) and 6-311 + G(2

  3. Spectra and structure of silicon containing compounds. XXXII. Raman and infrared spectra, conformational stability, vibrational assignment and ab initio calculations of n-propylsilane-d 0 and Si-d 3

    Science.gov (United States)

    Durig, James R.; Pan, Chunhua; Guirgis, Gamil A.

    2003-03-01

    The infrared (3100-40 cm -1) and Raman (3100-20 cm -1) spectra of gaseous and solid n-propylsilane, CH 3CH 2CH 2SiH 3 and the Si-d 3 isotopomer, CH 3CH 2CH 2SiD 3, have been recorded. Additionally, the Raman spectra of the liquids have been recorded and qualitative depolarization values obtained. Both the anti and gauche conformers have been identified in the fluid phases but only the anti conformer remains in the solid. Variable temperature (-105 to -150 °C) studies of the infrared spectra of n-propylsilane dissolved in liquid krypton have been recorded and the enthalpy difference has been determined to be 220±22 cm -1 (2.63±0.26 kJ mol -1) with the anti conformer the more stable form. A similar value of 234±23 cm -1 (2.80±0.28 kJ mol -1) was obtained for Δ H for the Si-d 3 isotopomer. At ambient temperature it is estimated that there is 30±2% of the gauche conformer present. The potential function governing the conformation interchange has been estimated from the far infrared spectral data, the enthalpy difference, and the dihedral angle of the gauche conformer, which is compared to the one predicted from ab initio MP2/6-31G(d) calculations. The barriers to conformational interchange are: 942, 970 and 716 cm -1 for the anti to gauche, gauche to gauche, and gauche to anti conformers, respectively. Relatively complete vibrational assignments are proposed for both the n-propylsilane-d 0 and Si-d 3 molecules based on the relative infrared and Raman spectral intensities, infrared band contours, depolarization ratios, and normal coordinate calculations. The geometrical parameters, harmonic force constants, vibrational frequencies, infrared intensities, Raman activities and depolarization ratios, and energy differences have been obtained for the anti and gauche conformers from ab initio MP2/6-31G(d) calculations. Structural parameters and energy differences have also been obtained utilizing the larger 6-311+G(d,p) and 6-311+G(2d,2p) basis sets. From the isolated

  4. Reactions driving conformational movements (molecular motors) in gels: conformational and structural chemical kinetics.

    Science.gov (United States)

    Otero, Toribio F

    2017-01-18

    In this perspective the empirical kinetics of conducting polymers exchanging anions and solvent during electrochemical reactions to get dense reactive gels is reviewed. The reaction drives conformational movements of the chains (molecular motors), exchange of ions and solvent with the electrolyte and structural (relaxation, swelling, shrinking and compaction) gel changes. Reaction-driven structural changes are identified and quantified from electrochemical responses. The empirical reaction activation energy (E a ), the reaction coefficient (k) and the reaction orders (α and β) change as a function of the conformational energy variation during the reaction. This conformational energy becomes an empirical magnitude. E a , k, α and β include and provide quantitative conformational and structural information. The chemical kinetics becomes structural chemical kinetics (SCK) for reactions driving conformational movements of the reactants. The electrochemically stimulated conformational relaxation model describes empirical results and some results from the literature for biochemical reactions. In parallel the development of an emerging technological world of soft, wet, multifunctional and biomimetic tools and anthropomorphic robots driven by reactions of the constitutive material, as in biological organs, can be now envisaged being theoretically supported by the kinetic model.

  5. Conformable Pressurized Structures : Design and Analysis

    NARCIS (Netherlands)

    Geuskens, F.J.J.M.M.

    2012-01-01

    There are many applications where volume needs to be pressurised within a geometrical space for which conventional pressure vessels do not provide suitable solutions. Applications are for example found in pressure cabins for Blended Wing Body Aircraft and conformable pressure vessels for an

  6. Structural alphabets derived from attractors in conformational space

    Directory of Open Access Journals (Sweden)

    Kleinjung Jens

    2010-02-01

    Full Text Available Abstract Background The hierarchical and partially redundant nature of protein structures justifies the definition of frequently occurring conformations of short fragments as 'states'. Collections of selected representatives for these states define Structural Alphabets, describing the most typical local conformations within protein structures. These alphabets form a bridge between the string-oriented methods of sequence analysis and the coordinate-oriented methods of protein structure analysis. Results A Structural Alphabet has been derived by clustering all four-residue fragments of a high-resolution subset of the protein data bank and extracting the high-density states as representative conformational states. Each fragment is uniquely defined by a set of three independent angles corresponding to its degrees of freedom, capturing in simple and intuitive terms the properties of the conformational space. The fragments of the Structural Alphabet are equivalent to the conformational attractors and therefore yield a most informative encoding of proteins. Proteins can be reconstructed within the experimental uncertainty in structure determination and ensembles of structures can be encoded with accuracy and robustness. Conclusions The density-based Structural Alphabet provides a novel tool to describe local conformations and it is specifically suitable for application in studies of protein dynamics.

  7. Structural Stability and Vibration

    DEFF Research Database (Denmark)

    Wiggers, Sine Leergaard; Pedersen, Pauli

    This book offers an integrated introduction to the topic of stability and vibration. Strikingly, it describes stability as a function of boundary conditions and eigenfrequency as a function of both boundary conditions and column force. Based on a post graduate course held by the author at the Uni...... and their derivation, thus stimulating them to write interactive and dynamic programs to analyze instability and vibrational modes....

  8. The conformational stability and flexibility of insulin with an additional intramolecular cross-link

    International Nuclear Information System (INIS)

    Brems, D.N.; Brown, P.L.; Nakagawa, S.H.; Tager, H.S.

    1991-01-01

    The conformational stability and flexibility of insulin containing a cross-link between the alpha-amino group of the A-chain to the epsilon-amino group of Lys29 of the B-chain was examined. The cross-link varied in length from 2 to 12 carbon atoms. The conformational stability was determined by guanidine hydrochloride-induced equilibrium denaturation and flexibility was assessed by H2O/D2O amide exchange. The cross-link has substantial effects on both conformational stability and flexibility which depend on its length. In general, the addition of a cross-link enhances conformational stability and decreases flexibility. The optimal length for enhanced stability and decreased flexibility was the 6-carbon link. For the 6-carbon link the Gibbs free energy of unfolding was 8.0 kcal/mol compared to 4.5 kcal/mol for insulin, and the amide exchange rate decreased by at least 3-fold. A very short cross-link (i.e. the 2-carbon link) caused conformational strain that was detectable by a lack of stabilization in the Gibbs free energy of unfolding and enhancement in the amide exchange rate compared to insulin. The effect of the cross-link length on insulin hydrodynamic properties is discussed relative to previously obtained receptor binding results

  9. BOMB STABILIZING STRUCTURE

    Science.gov (United States)

    Kelley, J.L.; Runyan, C.E.

    1963-12-10

    A stabilizinig structure capable of minimizing deviations of a falling body such as a bomb from desired trajectory is described. The structure comprises a fin or shroud arrangement of double-wedge configuration, the feeding portion being of narrow wedge shape and the after portion being of a wider wedge shape. The structure provides a force component for keeping the body on essentially desired trajectory throughout its fall. (AEC)

  10. Conformational stability of the epidermal growth factor (EGF) receptor as influenced by glycosylation, dimerization and EGF hormone binding.

    Science.gov (United States)

    Taylor, Eric S; Pol-Fachin, Laercio; Lins, Roberto D; Lower, Steven K

    2017-04-01

    The epidermal growth factor receptor (EGFR) is an important transmembrane glycoprotein kinase involved the initiation or perpetuation of signal transduction cascades within cells. These processes occur after EGFR binds to a ligand [epidermal growth factor (EGF)], thus inducing its dimerization and tyrosine autophosphorylation. Previous publications have highlighted the importance of glycosylation and dimerization for promoting proper function of the receptor and conformation in membranes; however, the effects of these associations on the protein conformational stability have not yet been described. Molecular dynamics simulations were performed to characterize the conformational preferences of the monomeric and dimeric forms of the EGFR extracellular domain upon binding to EGF in the presence and absence of N-glycan moieties. Structural stability analyses revealed that EGF provides the most conformational stability to EGFR, followed by glycosylation and dimerization, respectively. The findings also support that EGF-EGFR binding takes place through a large-scale induced-fitting mechanism. Proteins 2017; 85:561-570. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Crystal structures and conformers of CyMe4-BTBP

    Directory of Open Access Journals (Sweden)

    Lyczko Krzysztof

    2015-12-01

    Full Text Available The crystal structure of new conformation of the CyMe4-BTBP ligand (ttc has been presented. The ttt conformer of this compound in a form of THF solvate has been also crystallized. The geometries of six possible conformations (ttt, ttc, tct, tcc, ctc and ccc of the CyMe4-BTBP ligand have been modeled in the gas phase and in solutions (MeOH and H2O by DFT calculations using B3LYP/6-31G(d,p method. According to the calculations, in the three different media the conformers with trans orientation of the N atoms in the bipyridyl moiety are the most stable.

  12. Conformational stability analyses of alpha subunit I domain of LFA-1 and Mac-1.

    Directory of Open Access Journals (Sweden)

    Debin Mao

    Full Text Available β₂ integrin of lymphocyte function-associated antigen-1 (LFA-1 or macrophage-1 antigen (Mac-1 binds to their common ligand of intercellular adhesion molecule-1 (ICAM-1 and mediates leukocyte-endothelial cell (EC adhesions in inflammation cascade. Although the two integrins are known to have distinct functions, the corresponding micro-structural bases remain unclear. Here (steered-molecular dynamics simulations were employed to elucidate the conformational stability of α subunit I domains of LFA-1 and Mac-1 in different affinity states and relevant I domain-ICAM-1 interaction features. Compared with low affinity (LA Mac-1, the LA LFA-1 I domain was unstable in the presence or absence of ICAM-1 ligand, stemming from diverse orientations of its α₇-helix with different motifs of zipper-like hydrophobic junction between α₁- and α₇-helices. Meanwhile, spontaneous transition of LFA-1 I domain from LA state to intermediate affinity (IA state was first visualized. All the LA, IA, and high affinity (HA states of LFA-1 I domain and HA Mac-1 I domain were able to bind to ICAM-1 ligand effectively, while LA Mac-1 I domain was unfavorable for binding ligand presumably due to the specific orientation of S144 side-chain that capped the MIDAS ion. These results furthered our understanding in correlating the structural bases with their functions of LFA-1 and Mac-1 integrins from the viewpoint of I domain conformational stability and of the characteristics of I domain-ICAM-1 interactions.

  13. The impact of N-glycosylation on conformation and stability of immunoglobulin Y from egg yolk.

    Science.gov (United States)

    Sheng, Long; He, Zhenjiao; Chen, Jiahui; Liu, Yaofa; Ma, Meihu; Cai, Zhaoxia

    2017-03-01

    Immunoglobulin Y (IgY) is a new therapeutic antibody, and its applications in industry are very broad. To provide insight into the effects of N-glycosylation on IgY, its conformation and stability were studied. In this research, IgY was extracted from egg yolk and then digested by peptide-N4-(N-acetyl-beta-glucosaminyl) asparagine-amidase. SDS-PAGE and infrared absorption spectrum showed that carbohydrates were distinctly reduced after enzymolysis. The circular dichroism spectrum indicated that the IgY molecule became more flexible and disordered after removal of N-glycan. The fluorescence intensity revealed that Trp residues were buried in a more hydrophobic environment after disposal of N-glycan. Storage stability decreased with the removal of oligosaccharide chains based on size-exclusion chromatography analysis. Deglycosylated IgY exhibited less resistance to guanidine hydrochloride-induced unfolding. After deglycosylation, IgY was more sensitive to pepsin. Therefore, N-glycosylation played an important role in the maintenance of the structure and stability of IgY. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. An Improved Methodology for Multidimensional High-Throughput Preformulation Characterization of Protein Conformational Stability

    Science.gov (United States)

    Maddux, Nathaniel R.; Rosen, Ilan T.; Hu, Lei; Olsen, Christopher M.; Volkin, David B.; Middaugh, C. Russell

    2013-01-01

    The Empirical Phase Diagram (EPD) technique is a vector-based multidimensional analysis method for summarizing large data sets from a variety of biophysical techniques. It can be used to provide comprehensive preformulation characterization of a macromolecule’s higher-order structural integrity and conformational stability. In its most common mode, it represents a type of stimulus-response diagram using environmental variables such as temperature, pH, and ionic strength as the stimulus, with alterations in macromolecular structure being the response. Until now EPD analysis has not been available in a high throughput mode because of the large number of experimental techniques and environmental stressor/stabilizer variables typically employed. A new instrument has been developed that combines circular dichroism, UV-absorbance, fluorescence spectroscopy and light scattering in a single unit with a 6-position temperature controlled cuvette turret. Using this multifunctional instrument and a new software system we have generated EPDs for four model proteins. Results confirm the reproducibility of the apparent phase boundaries and protein behavior within the boundaries. This new approach permits two EPDs to be generated per day using only 0.5 mg of protein per EPD. Thus, the new methodology generates reproducible EPDs in high-throughput mode, and represents the next step in making such determinations more routine. PMID:22447621

  15. Investigating the conformational stability of prion strains through a kinetic replication model.

    Directory of Open Access Journals (Sweden)

    Mattia Zampieri

    2009-07-01

    Full Text Available Prion proteins are known to misfold into a range of different aggregated forms, showing different phenotypic and pathological states. Understanding strain specificities is an important problem in the field of prion disease. Little is known about which PrP(Sc structural properties and molecular mechanisms determine prion replication, disease progression and strain phenotype. The aim of this work is to investigate, through a mathematical model, how the structural stability of different aggregated forms can influence the kinetics of prion replication. The model-based results suggest that prion strains with different conformational stability undergoing in vivo replication are characterizable in primis by means of different rates of breakage. A further role seems to be played by the aggregation rate (i.e. the rate at which a prion fibril grows. The kinetic variability introduced in the model by these two parameters allows us to reproduce the different characteristic features of the various strains (e.g., fibrils' mean length and is coherent with all experimental observations concerning strain-specific behavior.

  16. Vibrational spectrum, ab initio calculations, conformational stabilities and assignment of fundamentals of 1,2-dibromopropane

    Science.gov (United States)

    LaPlante, Arthur J.; Stidham, Howard D.

    2009-10-01

    The mid and far infrared and the Raman spectrum of 1,2-dibromopropane is reported in solid, liquid and gas. Several bands reported by earlier workers are not present in the spectrum of the purified material. Ab initio calculations of optimized geometry, energy, dipole moment, molar volume, vibrational spectrum and normal coordinate calculation were performed using the density functional B3LYP/6-311++g(3df,2pd), and the results used to assist a complete assignment of the 81 fundamental modes of vibrations of the three conformers of 1,2-dibromopropane. Relative energies found conformer A the lowest with G and G' at 815.6 and 871.4 cm -1 higher. The temperature dependence of the Raman spectrum of the liquid was investigated in the CCC bending region and the relative energies determined. It was found that the G' and G conformers lie 236 ± 11 and 327 ±11 cm -1, respectively above the A conformer, leading to the room temperature composition of the liquid as A, 65 ± 1; G', 21 ± 1; G, 14 ± 1%. It is apparent that the calculated highest energy conformer G' is stabilized more than the G conformer in the liquid. The G' conformer has the lowest molar volume effectively changing the interaction distance between conformers in the liquid, and enhancing the effect of its dipole moment.

  17. New "sandwich" structures conformed from three dimensional

    Directory of Open Access Journals (Sweden)

    Alba, Juan J.

    1996-03-01

    Full Text Available Poor interlaminar properties as well as poor-skin-to-core adhesion properties are very often the common existing problems we find when designing with "sandwich" structures. A new type of 3D-fabric "sandwich" structure is being developed in order to avoid these problems. Although the manufacturing process is very simple, a very complex "sandwich" structure is obtained as a result of the complexity of the 3D-fabric used. This 3D-fabric is a 3D woven glass fabric produced on velvet weaving machines with glass yarns. It is an integrally woven "sandwich" laminate for all kinds of composite products. The strength of the vertical fibers makes, that also after impregnation with a resin matrix, the "sandwich" structure is maintained. The result is a laminate with high strength and stiffness and low weight. On each side of this "sandwich" laminate additional reinforcement materials can be laminated and a synthetic foam can be injected in the hollow structure. This will allow to establish the mechanical properties of a finished product.

    Las pobres propiedades, tanto interlaminares como de adhesión entre piel y núcleo, constituyen uno de los grandes problemas cuando se diseñan estructuras utilizando paneles tipo "sandwich". Un nuevo tipo de panel "sandwich", configurado a partir de tejidos tridimensionales, está siendo desarrollado en la actualidad con el objetivo de eliminar esos problemas. Aunque el proceso de fabricación es muy simple, el panel "sandwich" obtenido es de estructura compleja, como resultado de la complejidad del tejido tridimensional utilizado. Este tejido tridimensional (3D es un tejido de fibra de vidrio producido en máquinas de tejer especializadas. La resistencia de las fibras verticales hace que, después de la impregnación con una resina, se mantenga la configuración tipo "sandwich". El resultado es un laminado de alta resistencia, gran rigidez y bajo peso. Sobre cada uno de los lados del panel "sandwich" se pueden

  18. Monomeric banana lectin at acidic pH overrules conformational stability of its native dimeric form.

    Directory of Open Access Journals (Sweden)

    Javed M Khan

    Full Text Available Banana lectin (BL is a homodimeric protein categorized among jacalin-related family of lectins. The effect of acidic pH was examined on conformational stability of BL by using circular dichroism, intrinsic fluorescence, 1-anilino-8-napthalene sulfonate (ANS binding, size exclusion chromatography (SEC and dynamic light scattering (DLS. During acid denaturation of BL, the monomerization of native dimeric protein was found at pH 2.0. The elution profile from SEC showed two different peaks (59.65 ml & 87.98 ml at pH 2.0 while single peak (61.45 ml at pH 7.4. The hydrodynamic radii (R h of native BL was 2.9 nm while at pH 2.0 two species were found with R h of 1.7 and 3.7 nm. Furthermore at, pH 2.0 the secondary structures of BL remained unaltered while tertiary structure was significantly disrupted with the exposure of hydrophobic clusters confirming the existence of molten globule like state. The unfolding of BL with different subunit status was further evaluated by urea and temperature mediated denaturation to check their stability. As inferred from high Cm and ΔG values, the monomeric form of BL offers more resistance towards chemical denaturation than the native dimeric form. Besides, dimeric BL exhibited a Tm of 77°C while no loss in secondary structures was observed in monomers even up to 95°C. To the best of our knowledge, this is the first report on monomeric subunit of lectins showing more stability against denaturants than its native dimeric state.

  19. PAK4 crystal structures suggest unusual kinase conformational movements.

    Science.gov (United States)

    Zhang, Eric Y; Ha, Byung Hak; Boggon, Titus J

    2018-02-01

    In order for protein kinases to exchange nucleotide they must open and close their catalytic cleft. These motions are associated with rotations of the N-lobe, predominantly around the 'hinge region'. We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077). We find an unusual motion between the N-lobe and C-lobe of PAK4 that manifests as a partial unwinding of helix αC. Principal component analysis of the crystal structures rationalizes these movements into three major states, and analysis of the kinase hydrophobic spines indicates concerted movements that create an accessible back pocket cavity. The conformational changes that we observe for PAK4 differ from previous descriptions of kinase motions, and although we observe these differences in crystal structures there is the possibility that the movements observed may suggest a diversity of kinase conformational changes associated with regulation. Protein kinases are key signaling proteins, and are important drug targets, therefore understanding their regulation is important for both basic research and clinical points of view. In this study, we observe unusual conformational 'hinging' for protein kinases. Hinging, the opening and closing of the kinase sub-domains to allow nucleotide binding and release, is critical for proper kinase regulation and for targeted drug discovery. We determine new crystal structures of PAK4, an important Rho-effector kinase, and conduct analyses of these and previously determined structures. We find that PAK4 crystal structures can be classified into specific conformational groups, and that these groups are associated with previously unobserved hinging motions and an unusual conformation for the kinase hydrophobic core. Our findings therefore indicate that there may be a diversity of kinase hinging motions, and that these may

  20. Structure and conformational changes of crotamine

    International Nuclear Information System (INIS)

    Beltran, J.R.; Mascarenhas, Y.P.; Cid, H.; Craievich, A.F.; Laure, C.J.

    1983-01-01

    The secondary structure of crotamine is predicted by the simultaneous use of the statistical method of Chou and Fasman and the method of hydrofobicity profiles resulting in 19% of helix- and 45% of β-structures, in agreement both with previous results obtained from ORD and laser spectroscopy. It allows for the three disulphide bridges and is consistent with a long ellipsoidal shape for the molecule. From SAXS curves measured at several concentrations the radius of gyration, volume and surface of the molecule are obtained. The knowledge of these parameters enables one to conclude that the overall shape of the crotamine molecule can be described by a prolate (long) ellipsoide of semi-axis a, a and νa with ν = 2.3, in agreement with the above prediction. The radius of gyration of crotamine is also determined as a function of pH. An important change found for pH values from 9.5 to 12.5 is atributed to a dominant effect of molecular aggregation. (Author) [pt

  1. 18 CFR 415.51 - Prior non-conforming structures.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Prior non-conforming structures. 415.51 Section 415.51 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION... damaged by any means, including a flood, to the extent of 50 percent or more of its market value at that...

  2. Braided structure in 4-dimensional conformal quantum field theory

    International Nuclear Information System (INIS)

    Schroer, Bert

    2001-03-01

    Higher dimensional conformal QFT possesses an intersting braided structure which different from the d=1+1 models, is restricted to the timelike region and therefore easily escapes euclidean action methods. It lies behind the spectrum of anamalous which may be viewed as a kind of substitute for a missing particle interpretation in the presence of interactions. (author)

  3. Non-relativistic conformal symmetries and Newton-Cartan structures

    International Nuclear Information System (INIS)

    Duval, C; Horvathy, P A

    2009-01-01

    This paper provides us with a unifying classification of the conformal infinitesimal symmetries of non-relativistic Newton-Cartan spacetime. The Lie algebras of non-relativistic conformal transformations are introduced via the Galilei structure. They form a family of infinite-dimensional Lie algebras labeled by a rational 'dynamical exponent', z. The Schroedinger-Virasoro algebra of Henkel et al corresponds to z = 2. Viewed as projective Newton-Cartan symmetries, they yield, for timelike geodesics, the usual Schroedinger Lie algebra, for which z = 2. For lightlike geodesics, they yield, in turn, the Conformal Galilean Algebra (CGA) of Lukierski, Stichel and Zakrzewski (alias 'alt' of Henkel), with z = 1. Physical systems realizing these symmetries include, e.g. classical systems of massive and massless non-relativistic particles, and also hydrodynamics, as well as Galilean electromagnetism.

  4. Probing Conformational Stability and Dynamics of Erythroid and Nonerythroid Spectrin: Effects of Urea and Guanidine Hydrochloride

    Science.gov (United States)

    Patra, Malay; Mukhopadhyay, Chaitali; Chakrabarti, Abhijit

    2015-01-01

    We have studied the conformational stability of the two homologous membrane skeletal proteins, the erythroid and non-erythroid spectrins, in their dimeric and tetrameric forms respectively during unfolding in the presence of urea and guanidine hydrochloride (GuHCl). Fluorescence and circular dichroism (CD) spectroscopy have been used to study the changes of intrinsic tryptophan fluorescence, anisotropy, far UV-CD and extrinsic fluorescence of bound 1-anilinonapthalene-8-sulfonic acid (ANS). Chemical unfolding of both proteins were reversible and could be described as a two state transition. The folded erythroid spectrin and non-erythroid spectrin were directly converted to unfolded monomer without formation of any intermediate. Fluorescence quenching, anisotropy, ANS binding and dynamic light scattering data suggest that in presence of low concentrations of the denaturants (up-to 1M) hydrogen bonding network and van der Waals interaction play a role inducing changes in quaternary as well as tertiary structures without complete dissociation of the subunits. This is the first report of two large worm like, multi-domain proteins obeying twofold rule which is commonly found in small globular proteins. The free energy of stabilization (ΔGu H 2 0) for the dimeric spectrin has been 20 kcal/mol lesser than the tetrameric from. PMID:25617632

  5. Conformational analysis of cellobiose by electronic structure theories.

    Science.gov (United States)

    French, Alfred D; Johnson, Glenn P; Cramer, Christopher J; Csonka, Gábor I

    2012-03-01

    Adiabatic Φ/ψ maps for cellobiose were prepared with B3LYP density functional theory. A mixed basis set was used for minimization, followed with 6-31+G(d) single-point calculations, with and without SMD continuum solvation. Different arrangements of the exocyclic groups (38 starting geometries) were considered for each Φ/ψ point. The vacuum calculations agreed with earlier computational and experimental results on the preferred gas phase conformation (anti-Φ(H), syn-ψ(H)), and the results from the solvated calculations were consistent with the (syn Φ(H)/ψ(H) conformations from condensed phases (crystals or solutions). Results from related studies were compared, and there is substantial dependence on the solvation model as well as arrangements of exocyclic groups. New stabilizing interactions were revealed by Atoms-In-Molecules theory. Published by Elsevier Ltd.

  6. Ca and Mg binding induce conformational stability of Calfumirin-1 ...

    Indian Academy of Sciences (India)

    The thermal unfolding curves of wtCAF-1 monitored at neutral pH by CD spectroscopy are reversible and show ... These domains have either structurally dependent or independent Ca2+- ... that behave as a Ca2+ sensor protein, CaBP1 and.

  7. Structures of closed and open conformations of dimeric human ATM

    Science.gov (United States)

    Baretić, Domagoj; Pollard, Hannah K.; Fisher, David I.; Johnson, Christopher M.; Santhanam, Balaji; Truman, Caroline M.; Kouba, Tomas; Fersht, Alan R.; Phillips, Christopher; Williams, Roger L.

    2017-01-01

    ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase–related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, insulin signaling, and neurogenesis. Our electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic equilibrium between closed and open dimers. In the closed state, the PIKK regulatory domain blocks the peptide substrate–binding site, suggesting that this conformation may represent an inactive or basally active enzyme. The active site is held in this closed conformation by interaction with a long helical hairpin in the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related molecule. The open dimer has two protomers with only a limited contact interface, and it lacks the intermolecular interactions that block the peptide-binding site in the closed dimer. This suggests that the open conformation may be more active. The ATM structure shows the detailed topology of the regulator-interacting N-terminal helical solenoid. The ATM conformational dynamics shown by the structures represent an important step in understanding the enzyme regulation. PMID:28508083

  8. A theoretical and spectroscopic study of conformational structures of piroxicam

    Science.gov (United States)

    Souza, Kely Ferreira de; Martins, José A.; Pessine, Francisco B. T.; Custodio, Rogério

    2010-02-01

    Piroxicam (PRX) has been widely studied in an attempt to elucidate the causes and mechanisms of its side effects, mainly the photo-toxicity. In this paper fluorescence spectra in non-protic solvents and different polarities were carried out along with theoretical calculations. Preliminary potential surfaces of the keto and enol forms were obtained at AM1 level of theory providing the most stable conformers, which had their structure re-optimized through the B3LYP/CEP-31G(d,p) method. From the optimized structures, the electronic spectra were calculated using the TD-DFT method in vacuum and including the solvent effect through the PCM method and a single water molecule near PRX. A new potential surface was constructed to the enol tautomer at DFT level and the most stable conformers were submitted to the QST2 calculations. The experimental data showed that in apolar media, the solution fluorescence is raised. Based on conformational analysis for the two tautomers, keto and enol, the results indicated that the PRX-enol is the main tautomer related to the drug fluorescence, which is reinforced by the spectra results, as well as the interconvertion barrier obtained from the QST2 calculations. The results suggest that the PRX one of the enol conformers presents great possibility of involvement in the photo-toxicity mechanisms.

  9. Effects of sorbitol and glycerol on the structure, dynamics, and stability of Mycobacterium tuberculosis pyrazinamidase

    Directory of Open Access Journals (Sweden)

    Mehrnoosh Khajehzadeh

    2016-01-01

    Conclusion: It can be concluded that the native conformation of the enzyme was stabilized in the sorbitol and glycerol and tend to exclude from the PZase surface, forcing the enzyme to keep it in the compactly folded conformation. The glycerol molecules stabilized PZase by decreasing the loops flexibility and then compacting the enzyme structure. It appears that more stability of PZase in glycerol solution correlates with its amphiphilic orientation, which decreases the unfavorable interactions of hydrophobic regions.

  10. Ensemble refinement shows conformational flexibility in crystal structures of human complement factor D

    International Nuclear Information System (INIS)

    Forneris, Federico; Burnley, B. Tom; Gros, Piet

    2014-01-01

    Ensemble-refinement analysis of native and mutant factor D (FD) crystal structures indicates a dynamical transition in FD from a self-inhibited inactive conformation to a substrate-bound active conformation that is reminiscent of the allostery in thrombin. Comparison with previously observed dynamics in thrombin using NMR data supports the crystallographic ensembles. Human factor D (FD) is a self-inhibited thrombin-like serine proteinase that is critical for amplification of the complement immune response. FD is activated by its substrate through interactions outside the active site. The substrate-binding, or ‘exosite’, region displays a well defined and rigid conformation in FD. In contrast, remarkable flexibility is observed in thrombin and related proteinases, in which Na + and ligand binding is implied in allosteric regulation of enzymatic activity through protein dynamics. Here, ensemble refinement (ER) of FD and thrombin crystal structures is used to evaluate structure and dynamics simultaneously. A comparison with previously published NMR data for thrombin supports the ER analysis. The R202A FD variant has enhanced activity towards artificial peptides and simultaneously displays active and inactive conformations of the active site. ER revealed pronounced disorder in the exosite loops for this FD variant, reminiscent of thrombin in the absence of the stabilizing Na + ion. These data indicate that FD exhibits conformational dynamics like thrombin, but unlike in thrombin a mechanism has evolved in FD that locks the unbound native state into an ordered inactive conformation via the self-inhibitory loop. Thus, ensemble refinement of X-ray crystal structures may represent an approach alternative to spectroscopy to explore protein dynamics in atomic detail

  11. Saturating representation of loop conformational fragments in structure databanks

    Directory of Open Access Journals (Sweden)

    Fiser András

    2006-07-01

    Full Text Available Abstract Background Short fragments of proteins are fundamental starting points in various structure prediction applications, such as in fragment based loop modeling methods but also in various full structure build-up procedures. The applicability and performance of these approaches depend on the availability of short fragments in structure databanks. Results We studied the representation of protein loop fragments up to 14 residues in length. All possible query fragments found in sequence databases (Sequence Space were clustered and cross referenced with available structural fragments in Protein Data Bank (Structure Space. We found that the expansion of PDB in the last few years resulted in a dense coverage of loop conformational fragments. For each loops of length 8 in the current Sequence Space there is at least one loop in Structure Space with 50% or higher sequence identity. By correlating sequence and structure clusters of loops we found that a 50% sequence identity generally guarantees structural similarity. These percentages of coverage at 50% sequence cutoff drop to 96, 94, 68, 53, 33 and 13% for loops of length 9, 10, 11, 12, 13, and 14, respectively. There is not a single loop in the current Sequence Space at any length up to 14 residues that is not matched with a conformational segment that shares at least 20% sequence identity. This minimum observed identity is 40% for loops of 12 residues or shorter and is as high as 50% for 10 residue or shorter loops. We also assessed the impact of rapidly growing sequence databanks on the estimated number of new loop conformations and found that while the number of sequentially unique sequence segments increased about six folds during the last five years there are almost no unique conformational segments among these up to 12 residues long fragments. Conclusion The results suggest that fragment based prediction approaches are not limited any more by the completeness of fragments in databanks but

  12. The conformational stability and biophysical properties of the eukaryotic thioredoxins of Pisum sativum are not family-conserved.

    Directory of Open Access Journals (Sweden)

    David Aguado-Llera

    2011-02-01

    Full Text Available Thioredoxins (TRXs are ubiquitous proteins involved in redox processes. About forty genes encode TRX or TRX-related proteins in plants, grouped in different families according to their subcellular localization. For instance, the h-type TRXs are located in cytoplasm or mitochondria, whereas f-type TRXs have a plastidial origin, although both types of proteins have an eukaryotic origin as opposed to other TRXs. Herein, we study the conformational and the biophysical features of TRXh1, TRXh2 and TRXf from Pisum sativum. The modelled structures of the three proteins show the well-known TRX fold. While sharing similar pH-denaturations features, the chemical and thermal stabilities are different, being PsTRXh1 (Pisum sativum thioredoxin h1 the most stable isoform; moreover, the three proteins follow a three-state denaturation model, during the chemical-denaturations. These differences in the thermal- and chemical-denaturations result from changes, in a broad sense, of the several ASAs (accessible surface areas of the proteins. Thus, although a strong relationship can be found between the primary amino acid sequence and the structure among TRXs, that between the residue sequence and the conformational stability and biophysical properties is not. We discuss how these differences in the biophysical properties of TRXs determine their unique functions in pea, and we show how residues involved in the biophysical features described (pH-titrations, dimerizations and chemical-denaturations belong to regions involved in interaction with other proteins. Our results suggest that the sequence demands of protein-protein function are relatively rigid, with different protein-binding pockets (some in common for each of the three proteins, but the demands of structure and conformational stability per se (as long as there is a maintained core, are less so.

  13. The integrable structure of nonrational conformal field theory

    Energy Technology Data Exchange (ETDEWEB)

    Bytsko, A. [Steklov Mathematics Institute, St. Petersburg (Russian Federation); Teschner, J. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2009-02-15

    Using the example of Liouville theory, we show how the separation into left- and rightmoving degrees of freedom of a nonrational conformal field theory can be made explicit in terms of its integrable structure. The key observation is that there exist separate Baxter Q-operators for left- and right-moving degrees of freedom. Combining a study of the analytic properties of the Q-operators with Sklyanin's Separation of Variables Method leads to a complete characterization of the spectrum. Taking the continuum limit allows us in particular to rederive the Liouville reflection amplitude using only the integrable structure. (orig.)

  14. Particle versus field structure in conformal quantum field theories

    International Nuclear Information System (INIS)

    Schroer, Bert

    2000-06-01

    I show that a particle structure in conformal field theory is incompatible with interactions. As a substitute one has particle-like excitations whose interpolating fields have in addition to their canonical dimension an anomalous contribution. The spectra of anomalous dimension is given in terms of the Lorentz invariant quadratic invariant (compact mass operator) of a conformal generator R μ with pure discrete spectrum. The perturbative reading of R o as a Hamiltonian in its own right, associated with an action in a functional integral setting naturally leads to the Ad S formulation. The formal service role of Ad S in order to access C QFT by a standard perturbative formalism (without being forced to understand first massive theories and then taking their scale-invariant limit) vastly increases the realm of conventionally accessible 4-dim. C QFT beyond those for which one had to use Lagrangians with supersymmetry in order to have a vanishing Beta-function. (author)

  15. On the effect of hydrostatic pressure on the conformational stability of globular proteins.

    Science.gov (United States)

    Graziano, Giuseppe

    2015-12-01

    The model developed for cold denaturation (Graziano, PCCP 2010, 12, 14245-14252) is extended to rationalize the dependence of protein conformational stability upon hydrostatic pressure, at room temperature. A pressure- volume work is associated with the process of cavity creation for the need to enlarge the liquid volume against hydrostatic pressure. This contribution destabilizes the native state that has a molecular volume slightly larger than the denatured state due to voids existing in the protein core. Therefore, there is a hydrostatic pressure value at which the pressure-volume contribution plus the conformational entropy loss of the polypeptide chain are able to overwhelm the stabilizing gain in translational entropy of water molecules, due to the decrease in water accessible surface area upon folding, causing denaturation. © 2015 Wiley Periodicals, Inc.

  16. Protein Loop Structure Prediction Using Conformational Space Annealing.

    Science.gov (United States)

    Heo, Seungryong; Lee, Juyong; Joo, Keehyoung; Shin, Hang-Cheol; Lee, Jooyoung

    2017-05-22

    We have developed a protein loop structure prediction method by combining a new energy function, which we call E PLM (energy for protein loop modeling), with the conformational space annealing (CSA) global optimization algorithm. The energy function includes stereochemistry, dynamic fragment assembly, distance-scaled finite ideal gas reference (DFIRE), and generalized orientation- and distance-dependent terms. For the conformational search of loop structures, we used the CSA algorithm, which has been quite successful in dealing with various hard global optimization problems. We assessed the performance of E PLM with two widely used loop-decoy sets, Jacobson and RAPPER, and compared the results against the DFIRE potential. The accuracy of model selection from a pool of loop decoys as well as de novo loop modeling starting from randomly generated structures was examined separately. For the selection of a nativelike structure from a decoy set, E PLM was more accurate than DFIRE in the case of the Jacobson set and had similar accuracy in the case of the RAPPER set. In terms of sampling more nativelike loop structures, E PLM outperformed E DFIRE for both decoy sets. This new approach equipped with E PLM and CSA can serve as the state-of-the-art de novo loop modeling method.

  17. Lid opening and conformational stability of T1 Lipase is mediated by increasing chain length polar solvents

    Directory of Open Access Journals (Sweden)

    Jonathan Maiangwa

    2017-05-01

    Full Text Available The dynamics and conformational landscape of proteins in organic solvents are events of potential interest in nonaqueous process catalysis. Conformational changes, folding transitions, and stability often correspond to structural rearrangements that alter contacts between solvent molecules and amino acid residues. However, in nonaqueous enzymology, organic solvents limit stability and further application of proteins. In the present study, molecular dynamics (MD of a thermostable Geobacillus zalihae T1 lipase was performed in different chain length polar organic solvents (methanol, ethanol, propanol, butanol, and pentanol and water mixture systems to a concentration of 50%. On the basis of the MD results, the structural deviations of the backbone atoms elucidated the dynamic effects of water/organic solvent mixtures on the equilibrium state of the protein simulations in decreasing solvent polarity. The results show that the solvent mixture gives rise to deviations in enzyme structure from the native one simulated in water. The drop in the flexibility in H2O, MtOH, EtOH and PrOH simulation mixtures shows that greater motions of residues were influenced in BtOH and PtOH simulation mixtures. Comparing the root mean square fluctuations value with the accessible solvent area (SASA for every residue showed an almost correspondingly high SASA value of residues to high flexibility and low SASA value to low flexibility. The study further revealed that the organic solvents influenced the formation of more hydrogen bonds in MtOH, EtOH and PrOH and thus, it is assumed that increased intraprotein hydrogen bonding is ultimately correlated to the stability of the protein. However, the solvent accessibility analysis showed that in all solvent systems, hydrophobic residues were exposed and polar residues tended to be buried away from the solvent. Distance variation of the tetrahedral intermediate packing of the active pocket was not conserved in organic solvent

  18. MOLECULAR STRUCTURE AND STABILITY E. Vessally* Payame ...

    African Journals Online (AJOL)

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    planar conformers are also found for NO, CO, SiO, GeO, O, C, Si, Ge. Isodesmic reactions to determine the stabilities of XO and X are considered. Nuclear independent chemical shifts, NICS, are calculated for the investigation of the homo-aromatic character of XO and X. The optimised geometries show the bonding in the.

  19. Concurrent Increases and Decreases in Local Stability and Conformational Heterogeneity in Cu, Zn Superoxide Dismutase Variants Revealed by Temperature-Dependence of Amide Chemical Shifts.

    Science.gov (United States)

    Doyle, Colleen M; Rumfeldt, Jessica A; Broom, Helen R; Sekhar, Ashok; Kay, Lewis E; Meiering, Elizabeth M

    2016-03-08

    The chemical shifts of backbone amide protons in proteins are sensitive reporters of local structural stability and conformational heterogeneity, which can be determined from their readily measured linear and nonlinear temperature-dependences, respectively. Here we report analyses of amide proton temperature-dependences for native dimeric Cu, Zn superoxide dismutase (holo pWT SOD1) and structurally diverse mutant SOD1s associated with amyotrophic lateral sclerosis (ALS). Holo pWT SOD1 loses structure with temperature first at its periphery and, while having extremely high global stability, nevertheless exhibits extensive conformational heterogeneity, with ∼1 in 5 residues showing evidence for population of low energy alternative states. The holo G93A and E100G ALS mutants have moderately decreased global stability, whereas V148I is slightly stabilized. Comparison of the holo mutants as well as the marginally stable immature monomeric unmetalated and disulfide-reduced (apo(2SH)) pWT with holo pWT shows that changes in the local structural stability of individual amides vary greatly, with average changes corresponding to differences in global protein stability measured by differential scanning calorimetry. Mutants also exhibit altered conformational heterogeneity compared to pWT. Strikingly, substantial increases as well as decreases in local stability and conformational heterogeneity occur, in particular upon maturation and for G93A. Thus, the temperature-dependence of amide shifts for SOD1 variants is a rich source of information on the location and extent of perturbation of structure upon covalent changes and ligand binding. The implications for potential mechanisms of toxic misfolding of SOD1 in disease and for general aspects of protein energetics, including entropy-enthalpy compensation, are discussed.

  20. Switch region for pathogenic structural change in conformational disease and its prediction.

    Directory of Open Access Journals (Sweden)

    Xin Liu

    2010-01-01

    Full Text Available Many diseases are believed to be related to abnormal protein folding. In the first step of such pathogenic structural changes, misfolding occurs in regions important for the stability of the native structure. This destabilizes the normal protein conformation, while exposing the previously hidden aggregation-prone regions, leading to subsequent errors in the folding pathway. Sites involved in this first stage can be deemed switch regions of the protein, and can represent perfect binding targets for drugs to block the abnormal folding pathway and prevent pathogenic conformational changes. In this study, a prediction algorithm for the switch regions responsible for the start of pathogenic structural changes is introduced. With an accuracy of 94%, this algorithm can successfully find short segments covering sites significant in triggering conformational diseases (CDs and is the first that can predict switch regions for various CDs. To illustrate its effectiveness in dealing with urgent public health problems, the reason of the increased pathogenicity of H5N1 influenza virus is analyzed; the mechanisms of the pandemic swine-origin 2009 A(H1N1 influenza virus in overcoming species barriers and in infecting large number of potential patients are also suggested. It is shown that the algorithm is a potential tool useful in the study of the pathology of CDs because: (1 it can identify the origin of pathogenic structural conversion with high sensitivity and specificity, and (2 it provides an ideal target for clinical treatment.

  1. Distribution, transition and thermodynamic stability of protein conformations in the denaturant-induced unfolding of proteins.

    Science.gov (United States)

    Bian, Liujiao; Ji, Xu

    2014-01-01

    Extensive and intensive studies on the unfolding of proteins require appropriate theoretical model and parameter to clearly illustrate the feature and characteristic of the unfolding system. Over the past several decades, four approaches have been proposed to describe the interaction between proteins and denaturants, but some ambiguity and deviations usually occur in the explanation of the experimental data. In this work, a theoretical model was presented to show the dependency of the residual activity ratio of the proteins on the molar denaturant concentration. Through the characteristic unfolding parameters ki and Δmi in this model, the distribution, transition and thermodynamic stability of protein conformations during the unfolding process can be quantitatively described. This model was tested with the two-state unfolding of bovine heart cytochrome c and the three-state unfolding of hen egg white lysozyme induced by both guanidine hydrochloride and urea, the four-state unfolding of bovine carbonic anhydrase b induced by guanidine hydrochloride and the unfolding of some other proteins induced by denaturants. The results illustrated that this model could be used accurately to reveal the distribution and transition of protein conformations in the presence of different concentrations of denaturants and to evaluate the unfolding tendency and thermodynamic stability of different conformations. In most denaturant-induced unfolding of proteins, the unfolding became increasingly hard in next transition step and the proteins became more unstable as they attained next successive stable conformation. This work presents a useful method for people to study the unfolding of proteins and may be used to describe the unfolding and refolding of other biopolymers induced by denaturants, inducers, etc.

  2. Structural and conformational study of polysaccharides by nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Bossennec, Veronique

    1989-01-01

    As some natural polysaccharides are involved in important biological processes, the use of nuclear magnetic resonance appears to be an adapted mean to determine their structure-activity relationship and is therefore the object of this research thesis. By using bi-dimensional proton-based NMR techniques, it is possible to identify minority saccharide units, to determine their conformation, and to identify units which they are bound to. The author reports the application of these methods to swine mucosa heparin, and to heparins displaying a high and low anticoagulant activity. The dermatan sulphate has also been studied, and the NMR analysis allowed some polymer structure irregularities to be identified. A molecular modelling of dermatan sulphate has been performed [fr

  3. Characterization of molecular determinants of the conformational stability of macrophage migration inhibitory factor: leucine 46 hydrophobic pocket.

    Directory of Open Access Journals (Sweden)

    Farah El-Turk

    Full Text Available Macrophage Migration Inhibitory Factor (MIF is a key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer formation, is essential for its keto-enol tautomerase activity and probably mediates several of its interactions and biological activities, including its binding to its receptor CD74 and activation of certain signaling pathways. Therefore, understanding the molecular factors governing the oligomerization of MIF and the role of quaternary structure in modulating its structural stability and multifunctional properties is crucial for understanding the function of MIF in health and disease. Herein, we describe highly conserved intersubunit interactions involving the hydrophobic packing of the side chain of Leu46 onto the β-strand β3 of one monomer within a hydrophobic pocket from the adjacent monomer constituted by residues Arg11, Val14, Phe18, Leu19, Val39, His40, Val41, Val42, and Pro43. To elucidate the structural significance of these intersubunit interactions and their relative contribution to MIF's trimerization, structural stability and catalytic activity, we generated three point mutations where Leu46 was replaced by glycine (L46G, alanine (L46A and phenylalanine (L46F, and their structural properties, stability, oligomerization state, and catalytic activity were characterized using a battery of biophysical methods and X-ray crystallography. Our findings provide new insights into the role of the Leu46 hydrophobic pocket in stabilizing the conformational state of MIF in solution. Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state.

  4. Intramolecular interactions stabilizing compact conformations of the intrinsically disordered kinase-inhibitor domain of Sic1: a molecular dynamics investigation.

    Directory of Open Access Journals (Sweden)

    Matteo eLambrughi

    2012-11-01

    Full Text Available Cyclin-dependent kinase inhibitors (CKIs are key regulatory proteins of the eukaryotic cell cycle, which modulate cyclin-dependent kinase (Cdk activity. CKIs perform their inhibitory effect by the formation of ternary complexes with a target kinase and its cognate cyclin. These regulators generally belong to the class of intrinsically disordered proteins (IDPs, which lack a well-defined and organized three-dimensional structure in their free state, undergoing folding upon binding to specific partners. Unbound IDPs are not merely random-coil structures, but can present intrinsically folded structural units (IFSUs and collapsed conformations. These structural features can be relevant to protein function in vivo.The yeast CKI Sic1 is a 284-amino acid IDP that binds to Cdk1 in complex with the Clb5,6 cyclins, preventing phosphorylation of G1 substrates and, therefore, entrance to the S phase. Sic1 degradation, triggered by multiple phosphorylation events, promotes cell-cycle progression. Previous experimental studies pointed out a propensity of Sic1 and its isolated domains to populate both extended and compact conformations. The present contribution provides models of the compact conformations of the Sic1 kinase-inhibitory domain (KID by all-atom molecular-dynamics simulations in explicit solvent and in the absence of interactors. The results are integrated by spectroscopic and spectrometric data. Helical IFSUs are identified, along with networks of intramolecular interactions. The results identify a group of hub residues and electrostatic interactions which are likely to be involved in the stabilization of globular states.

  5. Conformational energy calculations on polypeptides and proteins: use of a statistical mechanical procedure for evaluating structure and properties.

    Science.gov (United States)

    Scheraga, H A; Paine, G H

    1986-01-01

    We are using a variety of theoretical and computational techniques to study protein structure, protein folding, and higher-order structures. Our earlier work involved treatments of liquid water and aqueous solutions of nonpolar and polar solutes, computations of the stabilities of the fundamental structures of proteins and their packing arrangements, conformations of small cyclic and open-chain peptides, structures of fibrous proteins (collagen), structures of homologous globular proteins, introduction of special procedures as constraints during energy minimization of globular proteins, and structures of enzyme-substrate complexes. Recently, we presented a new methodology for predicting polypeptide structure (described here); the method is based on the calculation of the probable and average conformation of a polypeptide chain by the application of equilibrium statistical mechanics in conjunction with an adaptive, importance sampling Monte Carlo algorithm. As a test, it was applied to Met-enkephalin.

  6. A quantum group structure in integrable conformal field theories

    International Nuclear Information System (INIS)

    Smit, D.J.

    1990-01-01

    We discuss a quantization prescription of the conformal algebras of a class of d=2 conformal field theories which are integrable. We first give a geometrical construction of certain extensions of the classical Virasoro algebra, known as classical W algebras, in which these algebras arise as the Lie algebra of the second Hamiltonian structure of a generalized Korteweg-de Vries hierarchy. This fact implies that the W algebras, obtained as a reduction with respect to the nilpotent subalgebras of the Kac-Moody algebra, describe the intergrability of a Toda field theory. Subsequently we determine the coadjoint operators of the W algebras, and relate these to classical Yang-Baxter matrices. The quantization of these algebras can be carried out using the concept of a so-called quantum group. We derive the condition under which the representations of these quantum groups admit a Hilbert space completion by exploring the relation with the braid group. Then we consider a modification of the Miura transformation which we use to define a quantum W algebra. This leads to an alternative interpretation of the coset construction for Kac-Moody algebras in terms of nonlinear integrable hierarchies. Subsequently we use the connection between the induced braid group representations and the representations of the mapping class group of Riemann surfaces to identify an action of the W algebras on the moduli space of stable curves, and we give the invariants of this action. This provides a generalization of the situation for the Virasoro algebra, where such an invariant is given by the so-called Mumford form which describes the partition function of the bosonic string. (orig.)

  7. Quaternion analyticity and conformally Kaehlerian structure in Euclidean gravity

    International Nuclear Information System (INIS)

    Guersey, F.; Chia-Hsiung Tze

    1984-01-01

    Starting from the fact that the d = 4 Euclidean flat spacetime is conformally related to the Kaehler manifold H 2 xS 2 , we show the Euclidean Schwarzschild metric to be conformally related to another Kaehler manifold M 2 xS 2 with M 2 being conformal to H 2 in two dimensions. Both metrics which are conformally Kaehlerian, are form-invariant under the infinite parameter Fueter group, the Euclidean counterpart of Milne's group of clock regraduation. The associated Einstein's equations translate into Fueter's quaternionic analyticity. The latter leads to an infinite number of local continuity equations. (orig.)

  8. Flexible and conformable broadband metamaterial absorber with wide-angle and polarization stability for radar application

    Science.gov (United States)

    Chen, Huijie; Yang, Xiaoqing; Wu, Shiyue; Zhang, Di; Xiao, Hui; Huang, Kama; Zhu, Zhanxia; Yuan, Jianping

    2018-01-01

    In this work, a type of flexible, broadband electromagnetic microwave absorber is designed, fabricated and experimentally characterized. The absorber is composed of lumped resistors loaded frequency selective surface which is mounted on flexible substrate using silicone rubber and in turn backed by copper film. The simulated results show that an effective absorption (over 90%) bandwidth spans from 7.6 to 18.3 GHz, which covers both X (8-12 GHz) and Ku (12-18 GHz) bands, namely a 82.6% fraction bandwidth. And the bandwidth performs a good absorption response by varying the incident angle up to 60° for both TE and TM polarization. Moreover, the flexibility of the substrate enables the absorber conformably to bend and attach to cylinders of various radius without breakdown of the absorber. The designed structure has been fabricated and measured for both planar and conformable cases, and absorption responses show a good agreement of the broadband absorption feature with the simulated ones. This work has demonstrated specifically that proposed structure provides polarization-insensitive, wide-angle, flexible and conformable wideband absorption, which extends the absorber’s application to practical radar cross section reductions for radars and warships.

  9. Protease-sensitive conformers in broad spectrum of distinct PrPSc structures in sporadic Creutzfeldt-Jakob disease are indicator of progression rate.

    Directory of Open Access Journals (Sweden)

    Chae Kim

    2011-09-01

    Full Text Available The origin, range, and structure of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD, are largely unknown. To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD, we analyzed the conformational characteristics of protease-sensitive and protease-resistant fractions of the pathogenic prion protein (PrP(Sc using novel conformational methods derived from a conformation-dependent immunoassay (CDI. In 46 brains of patients homozygous for polymorphisms in the PRNP gene and exhibiting either Type 1 or Type 2 western blot pattern of the PrP(Sc, we identified an extensive array of PrP(Sc structures that differ in protease sensitivity, display of critical domains, and conformational stability. Surprisingly, in sCJD cases homozygous for methionine or valine at codon 129 of the PRNP gene, the concentration and stability of protease-sensitive conformers of PrP(Sc correlated with progression rate of the disease. These data indicate that sCJD brains exhibit a wide spectrum of PrP(Sc structural states, and accordingly argue for a broad spectrum of prion strains coding for different phenotypes. The link between disease duration, levels, and stability of protease-sensitive conformers of PrP(Sc suggests that these conformers play an important role in the pathogenesis of sCJD.

  10. NMR and modelling techniques in structural and conformation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Abraham, R J [Liverpool Univ. (United Kingdom)

    1994-12-31

    The use of Lanthanide Induced Shifts (L.I.S.) and modelling techniques in conformational analysis is presented. The use of Co{sup III} porphyrins as shift reagents is discussed, with examples of their use in the conformational analysis of some heterocyclic amines. (author) 13 refs., 9 figs.

  11. N-terminal diproline and charge group effects on the stabilization of helical conformation in alanine-based short peptides: CD studies with water and methanol as solvent.

    Science.gov (United States)

    Goyal, Bhupesh; Srivastava, Kinshuk Raj; Durani, Susheel

    2017-06-01

    Protein folding problem remains a formidable challenge as main chain, side chain and solvent interactions remain entangled and have been difficult to resolve. Alanine-based short peptides are promising models to dissect protein folding initiation and propagation structurally as well as energetically. The effect of N-terminal diproline and charged side chains is assessed on the stabilization of helical conformation in alanine-based short peptides using circular dichroism (CD) with water and methanol as solvent. A1 (Ac-Pro-Pro-Ala-Lys-Ala-Lys-Ala-Lys-Ala-NH 2 ) is designed to assess the effect of N-terminal homochiral diproline and lysine side chains to induce helical conformation. A2 (Ac-Pro-Pro-Glu-Glu-Ala-Ala-Lys-Lys-Ala-NH 2 ) and A3 (Ac-dPro-Pro-Glu-Glu-Ala-Ala-Lys-Lys-Ala-NH 2 ) with N-terminal homochiral and heterochiral diproline, respectively, are designed to assess the effect of Glu...Lys (i, i + 4) salt bridge interactions on the stabilization of helical conformation. The CD spectra of A1, A2 and A3 in water manifest different amplitudes of the observed polyproline II (PPII) signals, which indicate different conformational distributions of the polypeptide structure. The strong effect of solvent substitution from water to methanol is observed for the peptides, and CD spectra in methanol evidence A2 and A3 as helical folds. Temperature-dependent CD spectra of A1 and A2 in water depict an isodichroic point reflecting coexistence of two conformations, PPII and β-strand conformation, which is consistent with the previous studies. The results illuminate the effect of N-terminal diproline and charged side chains in dictating the preferences for extended-β, semi-extended PPII and helical conformation in alanine-based short peptides. The results of the present study will enhance our understanding on stabilization of helical conformation in short peptides and hence aid in the design of novel peptides with helical structures. Copyright © 2017 European Peptide

  12. Structure, stability and behaviour of nucleic acids in ionic liquids

    Science.gov (United States)

    Tateishi-Karimata, Hisae; Sugimoto, Naoki

    2014-01-01

    Nucleic acids have become a powerful tool in nanotechnology because of their conformational polymorphism. However, lack of a medium in which nucleic acid structures exhibit long-term stability has been a bottleneck. Ionic liquids (ILs) are potential solvents in the nanotechnology field. Hydrated ILs, such as choline dihydrogen phosphate (choline dhp) and deep eutectic solvent (DES) prepared from choline chloride and urea, are ‘green’ solvents that ensure long-term stability of biomolecules. An understanding of the behaviour of nucleic acids in hydrated ILs is necessary for developing DNA materials. We here review current knowledge about the structures and stabilities of nucleic acids in choline dhp and DES. Interestingly, in choline dhp, A–T base pairs are more stable than G–C base pairs, the reverse of the situation in buffered NaCl solution. Moreover, DNA triplex formation is markedly stabilized in hydrated ILs compared with aqueous solution. In choline dhp, the stability of Hoogsteen base pairs is comparable to that of Watson–Crick base pairs. Moreover, the parallel form of the G-quadruplex is stabilized in DES compared with aqueous solution. The behaviours of various DNA molecules in ILs detailed here should be useful for designing oligonucleotides for the development of nanomaterials and nanodevices. PMID:25013178

  13. MOLECULAR MODELING INDICATES THAT HOMOCYSTEINE INDUCES CONFORMATIONAL CHANGES IN THE STRUCTURE OF PUTATIVE TARGET PROTEINS

    Directory of Open Access Journals (Sweden)

    Yumnam Silla

    2015-09-01

    Full Text Available An elevated level of homocysteine, a reactive thiol containing amino acid is associated with a multitude of complex diseases. A majority (>80% of homocysteine in circulation is bound to protein cysteine residues. Although, till date only 21 proteins have been experimentally shown to bind with homocysteine, using an insilico approach we had earlier identified several potential target proteins that could bind with homocysteine. Shomocysteinylation of proteins could potentially alter the structure and/or function of the protein. Earlier studies have shown that binding of homocysteine to protein alters its function. However, the effect of homocysteine on the target protein structure has not yet been documented. In the present work, we assess conformational or structural changes if any due to protein homocysteinylation using two proteins, granzyme B (GRAB and junctional adhesion molecule 1 (JAM1, which could potentially bind to homocysteine. We, for the first time, constructed computational models of homocysteine bound to target proteins and monitored their structural changes using explicit solvent molecular dynamic (MD simulation. Analysis of homocysteine bound trajectories revealed higher flexibility of the active site residues and local structural perturbations compared to the unbound native structure’s simulation, which could affect the stability of the protein. In addition, secondary structure analysis of homocysteine bound trajectories also revealed disappearance of â-helix within the G-helix and linker region that connects between the domain regions (as defined in the crystal structure. Our study thus captures the conformational transitions induced by homocysteine and we suggest these structural alterations might have implications for hyperhomocysteinemia induced pathologies.

  14. Stability Analysis and Stabilization of Miduk Heap Leaching Structure, Iran

    Directory of Open Access Journals (Sweden)

    Mehdi Amini

    2013-06-01

    Full Text Available To construct copper heap leaching structures, a stepped heap of ore is placed over an isolated sloping surface and then washed with sulphuric acid. The isolated bed of such a heap consists of some natural and geosynthetic layers. Shear strength parameters between these layers are low, so they form the possible sliding surfaces of the heaps. Economic and environmental considerations call for studying such slides. In this study, firstly, results of the laboratory tests carried on the materials of the heap leaching structures bed are presented. Then, the instability mechanisms of such structures are investigated and proper approaches are summarized for their stabilization. Finally, stability of the Miduk copper heap is evaluated as a case history, and appropriate approaches and their effects are discussed for its stabilization.

  15. Tensegrity structures form, stability, and symmetry

    CERN Document Server

    Zhang, Jing Yao

    2015-01-01

    To facilitate a deeper understanding of tensegrity structures, this book focuses on their two key design problems: self-equilibrium analysis and stability investigation. In particular, high symmetry properties of the structures are extensively utilized. Conditions for self-equilibrium as well as super-stability of tensegrity structures are presented in detail. An analytical method and an efficient numerical method are given for self-equilibrium analysis of tensegrity structures: the analytical method deals with symmetric structures and the numerical method guarantees super-stability. Utilizing group representation theory, the text further provides analytical super-stability conditions for the structures that are of dihedral as well as tetrahedral symmetry. This book not only serves as a reference for engineers and scientists but is also a useful source for upper-level undergraduate and graduate students. Keeping this objective in mind, the presentation of the book is self-contained and detailed, with an abund...

  16. Conformational stabilization of the membrane embedded targeting domain of the lysosomal peptide transporter TAPL for solution NMR

    Energy Technology Data Exchange (ETDEWEB)

    Tumulka, Franz [Goethe-University Frankfurt, Institute of Biochemistry, Biocenter (Germany); Roos, Christian; Loehr, Frank [Goethe-University Frankfurt, Institute of Biophysical Chemistry, Biocenter (Germany); Bock, Christoph [Goethe-University Frankfurt, Institute of Biochemistry, Biocenter (Germany); Bernhard, Frank; Doetsch, Volker [Goethe-University Frankfurt, Institute of Biophysical Chemistry, Biocenter (Germany); Abele, Rupert, E-mail: abele@em.uni-frankfurt.de [Goethe-University Frankfurt, Institute of Biochemistry, Biocenter (Germany)

    2013-10-15

    The ATP binding cassette transporter TAPL translocates cytosolic peptides into the lumen of lysosomes driven by the hydrolysis of ATP. Functionally, this transporter can be divided into coreTAPL, comprising the transport function, and an additional N-terminal transmembrane domain called TMD0, which is essential for lysosomal targeting and mediates the interaction with the lysosomal associated membrane proteins LAMP-1 and LAMP-2. To elucidate the structure of this unique domain, we developed protocols for the production of high quantities of cell-free expressed TMD0 by screening different N-terminal expression tags. Independently of the amino acid sequence, high expression was detected for AU-rich sequences in the first seven codons, decreasing the free energy of RNA secondary structure formation at translation initiation. Furthermore, avoiding NGG codons in the region of translation initiation demonstrated a positive effect on expression. For NMR studies, conditions were optimized for high solubilization efficiency, long-term stability, and high quality spectra. A most critical step was the careful exchange of the detergent used for solubilization by the detergent dihexanoylphosphatidylcholine. Several constructs of different size were tested in order to stabilize the fold of TMD0 as well as to reduce the conformation exchange. NMR spectra with sufficient resolution and homogeneity were finally obtained with a TMD0 derivative only modified by a C-terminal His{sub 10}-tag and containing a codon optimized AT-rich sequence.

  17. Probing RNA native conformational ensembles with structural constraints

    DEFF Research Database (Denmark)

    Fonseca, Rasmus; van den Bedem, Henry; Bernauer, Julie

    2016-01-01

    substates, which are difficult to characterize experimentally and computationally. Here, we present an innovative, entirely kinematic computational procedure to efficiently explore the native ensemble of RNA molecules. Our procedure projects degrees of freedom onto a subspace of conformation space defined...

  18. Stability of the Wurtzite Structure

    DEFF Research Database (Denmark)

    Lawætz, Peter

    1972-01-01

    An analysis of available data for 20 wurtzite compounds of the ANB8-N type shows that the stability as compared with zinc blende is closely connected with deviations of the c / a ratio from the ideal value of 1.633. A simple qualitative model is proposed to account for this feature. The variation...... in c / a is then correlated with the charge parameter ZC / ℏωp, where Z is the (effective) valence, C Phillips's electronegativity difference, and ℏωp the plasma energy of the free-valence-electron gas. The results indicate that c / a may be predicted with an uncertainty of 0.1%....

  19. Sensitivity of system stability to model structure

    Science.gov (United States)

    Hosack, G.R.; Li, H.W.; Rossignol, P.A.

    2009-01-01

    A community is stable, and resilient, if the levels of all community variables can return to the original steady state following a perturbation. The stability properties of a community depend on its structure, which is the network of direct effects (interactions) among the variables within the community. These direct effects form feedback cycles (loops) that determine community stability. Although feedback cycles have an intuitive interpretation, identifying how they form the feedback properties of a particular community can be intractable. Furthermore, determining the role that any specific direct effect plays in the stability of a system is even more daunting. Such information, however, would identify important direct effects for targeted experimental and management manipulation even in complex communities for which quantitative information is lacking. We therefore provide a method that determines the sensitivity of community stability to model structure, and identifies the relative role of particular direct effects, indirect effects, and feedback cycles in determining stability. Structural sensitivities summarize the degree to which each direct effect contributes to stabilizing feedback or destabilizing feedback or both. Structural sensitivities prove useful in identifying ecologically important feedback cycles within the community structure and for detecting direct effects that have strong, or weak, influences on community stability. The approach may guide the development of management intervention and research design. We demonstrate its value with two theoretical models and two empirical examples of different levels of complexity. ?? 2009 Elsevier B.V. All rights reserved.

  20. The two C-terminal tyrosines stabilize occluded Na/K pump conformations containing Na or K ions.

    Science.gov (United States)

    Vedovato, Natascia; Gadsby, David C

    2010-07-01

    Interactions of the three transported Na ions with the Na/K pump remain incompletely understood. Na/K pump crystal structures show that the extended C terminus of the Na,K-adenosine triphosphatase (ATPase) alpha subunit directly contacts transmembrane helices. Deletion of the last five residues (KETYY in almost all Na/K pumps) markedly lowered the apparent affinity for Na activation of pump phosphorylation from ATP, a reflection of cytoplasmic Na affinity for forming the occluded E1P(Na3) conformation. ATPase assays further suggested that C-terminal truncations also interfere with low affinity Na interactions, which are attributable to extracellular effects. Because extracellular Na ions traverse part of the membrane's electric field to reach their binding sites in the Na/K pump, their movements generate currents that can be monitored with high resolution. We report here electrical measurements to examine how Na/K pump interactions with extracellular Na ions are influenced by C-terminal truncations. We deleted the last two (YY) or five (KESYY) residues in Xenopus laevis alpha1 Na/K pumps made ouabain resistant by either of two kinds of point mutations and measured their currents as 10-mM ouabain-sensitive currents in Xenopus oocytes after silencing endogenous Xenopus Na/K pumps with 1 microM ouabain. We found the low affinity inhibitory influence of extracellular Na on outward Na/K pump current at negative voltages to be impaired in all of the C-terminally truncated pumps. Correspondingly, voltage jump-induced transient charge movements that reflect pump interactions with extracellular Na ions were strongly shifted to more negative potentials; this signals a several-fold reduction of the apparent affinity for extracellular Na in the truncated pumps. Parallel lowering of Na affinity on both sides of the membrane argues that the C-terminal contacts provide important stabilization of the occluded E1P(Na3) conformation, regardless of the route of Na ion entry into the

  1. The role of PEG conformation in mixed layers: from protein corona substrate to steric stabilization avoiding protein adsorption

    Directory of Open Access Journals (Sweden)

    Joan Comenge

    2015-03-01

    Full Text Available Although nanoparticles (NPs have been traditionally modified with a single ligand layer, mixture of ligands might help to combine different functionalities and to further engineer the NP surface. A detailed study of the competition between an alkanethiol (11-mercaptoundecanoic acid and SH-PEG for the surface of AuNPs and the resultant behaviors of this model nanoconjugate is presented here. As a result, the physicochemical properties of these conjugates can be progressively tuned by controlling the composition and especially the conformation of the mixed monolayer. This has implications in the physiological stability. The controlled changes on the SH-PEG conformation rather than its concentration induce a change in the stabilization mechanism from electrostatic repulsion to steric hindrance, which changes the biological fate of NPs. Importantly, the adsorption of proteins on the conjugates can be tailored by tuning the composition and conformation of the mixed layer.

  2. The component structure of conformal supergravity invariants in six dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Butter, Daniel [Nikhef Theory Group,Science Park 105, 1098 XG Amsterdam (Netherlands); George and Cynthia Woods Mitchell Institute for Fundamental Physics and Astronomy,Texas A& M University,College Station, TX 77843 (United States); Novak, Joseph [Max-Planck-Institut für Gravitationsphysik, Albert-Einstein-Institut, Am Mühlenberg 1, D-14476 Golm (Germany); Tartaglino-Mazzucchelli, Gabriele [Instituut voor Theoretische Fysica, KU Leuven,Celestijnenlaan 200D, B-3001 Leuven (Belgium)

    2017-05-24

    In the recent paper https://arxiv.org/abs/1606.02921, the two invariant actions for 6D N=(1,0) conformal supergravity were constructed in superspace, corresponding to the supersymmetrization of C{sup 3} and C◻C. In this paper, we provide the translation from superspace to the component formulation of superconformal tensor calculus, and we give the full component actions of these two invariants. As a second application, we build the component form for the supersymmetric F◻F action coupled to conformal supergravity. Exploiting the fact that the N=(2,0) Weyl multiplet has a consistent truncation to N=(1,0), we then verify that there is indeed only a single N=(2,0) conformal supergravity invariant and reconstruct most of its bosonic terms by uplifting a certain linear combination of N=(1,0) invariants.

  3. Conformal field theory between supersymmetry and indecomposable structures

    Energy Technology Data Exchange (ETDEWEB)

    Eberle, H.

    2006-07-15

    This thesis considers conformal field theory in its supersymmetric extension as well as in its relaxation to logarithmic conformal field theory. This thesis is concerned with the subspace of K3 compactifications which is not well known yet. In particular, we inspect the intersection point of the Z{sub 2} and Z{sub 4} orbifold subvarieties within the K3 moduli space, explicitly identify the two corresponding points on the subvarieties geometrically, and give an explicit isomorphism of the three conformal field theory models located at that point, a specific Z{sub 2} and Z{sub 4} orbifold model as well as the Gepner model (2){sup 4}. We also prove the orthogonality of the two subvarieties at the intersection point. This is the starting point for the programme to investigate generic points in K3 moduli space. We use the coordinate identification at the intersection point in order to relate the coordinates of both subvarieties and to explicitly calculate a geometric geodesic between the two subvarieties as well as its generator. A generic point in K3 moduli space can be reached by such a geodesic originating at a known model. We also present advances on the conformal field theoretic side of deformations along such a geodesic using conformal deformation theory. Moreover, we regard a relaxation of conformal field theory to logarithmic conformal field theory. In particular, we study general augmented c{sub p,q} minimal models which generalise the well-known (augmented) c{sub p,1} model series. We calculate logarithmic nullvectors in both types of models. But most importantly, we investigate the low lying Virasoro representation content and fusion algebra of two general augmented c{sub p,q} models, the augmented c{sub 2,3}=0 model as well as the augmented Yang-Lee model at c{sub 2,5}=-22/5. In particular, the true vacuum representation is rather given by a rank 1 indecomposable but not irreducible subrepresentation of a rank 2 representation. We generalise these generic

  4. Conformal field theory between supersymmetry and indecomposable structures

    International Nuclear Information System (INIS)

    Eberle, H.

    2006-07-01

    This thesis considers conformal field theory in its supersymmetric extension as well as in its relaxation to logarithmic conformal field theory. This thesis is concerned with the subspace of K3 compactifications which is not well known yet. In particular, we inspect the intersection point of the Z 2 and Z 4 orbifold subvarieties within the K3 moduli space, explicitly identify the two corresponding points on the subvarieties geometrically, and give an explicit isomorphism of the three conformal field theory models located at that point, a specific Z 2 and Z 4 orbifold model as well as the Gepner model (2) 4 . We also prove the orthogonality of the two subvarieties at the intersection point. This is the starting point for the programme to investigate generic points in K3 moduli space. We use the coordinate identification at the intersection point in order to relate the coordinates of both subvarieties and to explicitly calculate a geometric geodesic between the two subvarieties as well as its generator. A generic point in K3 moduli space can be reached by such a geodesic originating at a known model. We also present advances on the conformal field theoretic side of deformations along such a geodesic using conformal deformation theory. Moreover, we regard a relaxation of conformal field theory to logarithmic conformal field theory. In particular, we study general augmented c p,q minimal models which generalise the well-known (augmented) c p,1 model series. We calculate logarithmic nullvectors in both types of models. But most importantly, we investigate the low lying Virasoro representation content and fusion algebra of two general augmented c p,q models, the augmented c 2,3 =0 model as well as the augmented Yang-Lee model at c 2,5 =-22/5. In particular, the true vacuum representation is rather given by a rank 1 indecomposable but not irreducible subrepresentation of a rank 2 representation. We generalise these generic examples to give the representation content and

  5. BRST structure of two dimensional conformal field theories

    International Nuclear Information System (INIS)

    Rivelles, V.O.

    1987-09-01

    We present a procedure to obtain the BRST charge for the representations of the Virassoro algebra. For C ≤ 1 the BRST charge has in general terms containing products of more than three ghosts. It is nilpotent for any allowed value of the central charge and conformal weight of the representation. (Author) [pt

  6. Molecular conformation and liquid structure of 2-propanol through ...

    Indian Academy of Sciences (India)

    The neutron diffraction data analysis of deuterated liquid 2-propanol at room temperature to ... 2-Propanol being a large molecule with twelve atomic sites, the conformation analysis is tricky ... A Sahoo1 S Sarkar1 P S R Krishna2 R N Joarder1.

  7. Acetylcholinesterase in motion : Visualizing conformational changes in crystal structures by a morphing procedure

    NARCIS (Netherlands)

    Zeev-Ben-Mordehai, T; Silman, I.; Sussman, J.L.

    In order to visualize and appreciate conformational changes between homologous three-dimensional (3D) protein structures or protein/inhibitor complexes, we have developed a user-friendly morphing procedure. It enabled us to detect coordinated conformational changes not easily discernible by analytic

  8. Deciphering the shape and deformation of secondary structures through local conformation analysis

    Directory of Open Access Journals (Sweden)

    Camproux Anne-Claude

    2011-02-01

    Full Text Available Abstract Background Protein deformation has been extensively analysed through global methods based on RMSD, torsion angles and Principal Components Analysis calculations. Here we use a local approach, able to distinguish among the different backbone conformations within loops, α-helices and β-strands, to address the question of secondary structures' shape variation within proteins and deformation at interface upon complexation. Results Using a structural alphabet, we translated the 3 D structures of large sets of protein-protein complexes into sequences of structural letters. The shape of the secondary structures can be assessed by the structural letters that modeled them in the structural sequences. The distribution analysis of the structural letters in the three protein compartments (surface, core and interface reveals that secondary structures tend to adopt preferential conformations that differ among the compartments. The local description of secondary structures highlights that curved conformations are preferred on the surface while straight ones are preferred in the core. Interfaces display a mixture of local conformations either preferred in core or surface. The analysis of the structural letters transition occurring between protein-bound and unbound conformations shows that the deformation of secondary structure is tightly linked to the compartment preference of the local conformations. Conclusion The conformation of secondary structures can be further analysed and detailed thanks to a structural alphabet which allows a better description of protein surface, core and interface in terms of secondary structures' shape and deformation. Induced-fit modification tendencies described here should be valuable information to identify and characterize regions under strong structural constraints for functional reasons.

  9. Deciphering the shape and deformation of secondary structures through local conformation analysis.

    Science.gov (United States)

    Baussand, Julie; Camproux, Anne-Claude

    2011-02-01

    Protein deformation has been extensively analysed through global methods based on RMSD, torsion angles and Principal Components Analysis calculations. Here we use a local approach, able to distinguish among the different backbone conformations within loops, α-helices and β-strands, to address the question of secondary structures' shape variation within proteins and deformation at interface upon complexation. Using a structural alphabet, we translated the 3 D structures of large sets of protein-protein complexes into sequences of structural letters. The shape of the secondary structures can be assessed by the structural letters that modeled them in the structural sequences. The distribution analysis of the structural letters in the three protein compartments (surface, core and interface) reveals that secondary structures tend to adopt preferential conformations that differ among the compartments. The local description of secondary structures highlights that curved conformations are preferred on the surface while straight ones are preferred in the core. Interfaces display a mixture of local conformations either preferred in core or surface. The analysis of the structural letters transition occurring between protein-bound and unbound conformations shows that the deformation of secondary structure is tightly linked to the compartment preference of the local conformations. The conformation of secondary structures can be further analysed and detailed thanks to a structural alphabet which allows a better description of protein surface, core and interface in terms of secondary structures' shape and deformation. Induced-fit modification tendencies described here should be valuable information to identify and characterize regions under strong structural constraints for functional reasons.

  10. Structural basis and kinetics of force-induced conformational changes of an αA domain-containing integrin.

    Directory of Open Access Journals (Sweden)

    Xue Xiang

    Full Text Available Integrin α(Lβ₂ (lymphocyte function-associated antigen, LFA-1 bears force upon binding to its ligand intercellular adhesion molecule 1 (ICAM-1 when a leukocyte adheres to vascular endothelium or an antigen presenting cell (APC during immune responses. The ligand binding propensity of LFA-1 is related to its conformations, which can be regulated by force. Three conformations of the LFA-1 αA domain, determined by the position of its α₇-helix, have been suggested to correspond to three different affinity states for ligand binding.The kinetics of the force-driven transitions between these conformations has not been defined and dynamically coupled to the force-dependent dissociation from ligand. Here we show, by steered molecular dynamics (SMD simulations, that the αA domain was successively transitioned through three distinct conformations upon pulling the C-terminus of its α₇-helix. Based on these sequential transitions, we have constructed a mathematical model to describe the coupling between the αA domain conformational changes of LFA-1 and its dissociation from ICAM-1 under force. Using this model to analyze the published data on the force-induced dissociation of single LFA-1/ICAM-1 bonds, we estimated the force-dependent kinetic rates of interstate transition from the short-lived to intermediate-lived and from intermediate-lived to long-lived states. Interestingly, force increased these transition rates; hence activation of LFA-1 was accelerated by pulling it via an engaged ICAM-1.Our study defines the structural basis for mechanical regulation of the kinetics of LFA-1 αA domain conformational changes and relates these simulation results to experimental data of force-induced dissociation of single LFA-1/ICAM-1 bonds by a new mathematical model, thus provided detailed structural and kinetic characterizations for force-stabilization of LFA-1/ICAM-1 interaction.

  11. Conformational co-dependence between Plasmodium berghei LCCL proteins promotes complex formation and stability.

    Science.gov (United States)

    Saeed, Sadia; Tremp, Annie Z; Dessens, Johannes T

    2012-10-01

    Malaria parasites express a conserved family of LCCL-lectin adhesive-like domain proteins (LAPs) that have essential functions in sporozoite transmission. In Plasmodium falciparum all six family members are expressed in gametocytes and form a multi-protein complex. Intriguingly, knockout of P. falciparum LCCL proteins adversely affects expression of other family members at protein, but not at mRNA level, a phenomenon termed co-dependent expression. Here, we investigate this in Plasmodium berghei by crossing a PbLAP1 null mutant parasite with a parasite line expressing GFP-tagged PbLAP3 that displays strong fluorescence in gametocytes. Selected and validated double mutants show normal synthesis and subcellular localization of PbLAP3::GFP. However, GFP-based fluorescence is dramatically reduced without PbLAP1 present, indicating that PbLAP1 and PbLAP3 interact. Moreover, absence of PbLAP1 markedly reduces the half-life of PbLAP3, consistent with a scenario of misfolding. These findings unveil a potential mechanism of conformational interdependence that facilitates assembly and stability of the functional LCCL protein complex. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. STRUCTURAL STABILITY AND ELECTRONIC STRUCTURE OF ...

    African Journals Online (AJOL)

    2012-12-31

    Dec 31, 2012 ... may be applications at high temperature strength and corrosion ... B2 structure, like that found in cesium-chloride (CsCl) and chemical formula RM, where R denotes a rare - earth element and M denotes a late transition metal ...

  13. Stability of bulk metallic glass structure

    Energy Technology Data Exchange (ETDEWEB)

    Jain, H.; Williams, D.B.

    2003-06-18

    The fundamental origins of the stability of the (Pd-Ni){sub 80}P{sub 20} bulk metallic glasses (BMGs), a prototype for a whole class of BMG formers, were explored. While much of the properties of their BMGs have been characterized, their glass-stability have not been explained in terms of the atomic and electronic structure. The local structure around all three constituent atoms was obtained, in a complementary way, using extended X-ray absorption fine structure (EXAFS), to probe the nearest neighbor environment of the metals, and extended energy loss fine structure (EXELFS), to investigate the environment around P. The occupied electronic structure was investigated using X-ray photoelectron spectroscopy (XPS). The (Pd-Ni){sub 80}P{sub 20} BMGs receive their stability from cumulative, and interrelated, effects of both atomic and electronic origin. The stability of the (Pd-Ni){sub 80}P{sub 20} BMGs can be explained in terms of the stability of Pd{sub 60}Ni{sub 20}P{sub 20} and Pd{sub 30}Ni{sub 50}P{sub 20}, glasses at the end of BMG formation. The atomic structure in these alloys is very similar to those of the binary phosphide crystals near x=0 and x=80, which are trigonal prisms of Pd or Ni atoms surrounding P atoms. Such structures are known to exist in dense, randomly-packed systems. The structure of the best glass former in this series, Pd{sub 40}Ni{sub 40}P{sub 20} is further described by a weighted average of those of Pd{sub 30}Ni{sub 50}P{sub 20} and Pd{sub 60}Ni{sub 20}P{sub 20}. Bonding states present only in the ternary alloys were found and point to a further stabilization of the system through a negative heat of mixing between Pd and Ni atoms. The Nagel and Tauc criterion, correlating a decrease in the density of states at the Fermi level with an increase in the glass stability, was consistent with greater stability of the Pd{sub x}Ni{sub (80-x)}P{sub 20} glasses with respect to the binary alloys of P. A valence electron concentration of 1.8 e/a, which

  14. Effect of Watson-Crick and Hoogsteen base pairing on the conformational stability of C8-phenoxyl-2'-deoxyguanosine adducts.

    Science.gov (United States)

    Millen, Andrea L; Churchill, Cassandra D M; Manderville, Richard A; Wetmore, Stacey D

    2010-10-14

    Bulky DNA addition products (adducts) formed through attack at the C8 site of guanine can adopt the syn orientation about the glycosidic bond due to changes in conformational stability or hydrogen-bonding preferences directly arising from the bulky group. Indeed, the bulky substituent may improve the stability of (non-native) Hoogsteen pairs. Therefore, such adducts often result in mutations upon DNA replication. This work examines the hydrogen-bonded pairs between the Watson-Crick and Hoogsteen faces of the ortho or para C8-phenoxyl-2'-deoxyguanosine adduct and each natural (undamaged) nucleobase with the goal to clarify the conformational preference of this type of damage, as well as provide insight into the likelihood of subsequent mutation events. B3LYP/6-311+G(2df,p)//B3LYP/6-31G(d) hydrogen-bond strengths were determined using both nucleobase and nucleoside models for adduct pairs, as well as the corresponding complexes involving natural 2'-deoxyguanosine. In addition to the magnitude of the binding strengths, the R(C1'···C1') distances and ∠(N9C1'C1') angles, as well as the degree of propeller-twist and buckle distortions, were carefully compared to the values observed in natural DNA strands. Due to structural changes in the adduct monomer upon inclusion of the sugar moiety, the monomer deformation energy significantly affects the relative hydrogen-bond strengths calculated with the nucleobase and nucleoside models. Therefore, we recommend the use of at least a nucleoside model to accurately evaluate hydrogen-bond strengths of base pairs involving flexible, bulky nucleobase adducts. Our results also emphasize the importance of considering both the magnitude of the hydrogen-bond strength and the structure of the base pair when predicting the preferential binding patterns of nucleobases. Using our best models, we conclude that the Watson-Crick face of the ortho phenoxyl adduct forms significantly more stable complexes than the Hoogsteen face, which

  15. A conformal gauge invariant functional for Weyl structures and the first variation formula

    OpenAIRE

    Ichiyama, Toshiyuki; Furuhata, Hitoshi; Urakawa, Hajime

    1999-01-01

    We consider a new conformal gauge invariant functional which is a natural curvature functional on the space of Weyl structures. We derive the first variation formula of its functional and characterize its critical points.

  16. Conformal Lightweight Antenna Structures for Aeronautical Communication Technologies

    Science.gov (United States)

    Meador, Mary Ann

    2017-01-01

    This project is to develop antennas which enable beyond line of sight (BLOS) command and control for UAVs. We will take advantage of newly assigned provisional Ku-band spectrum for UAVs and use unique antenna designs to avoid interference with ground systems. This will involve designing antennas with high isotropic effective radiated power (EIRP) and ultra-low sidelobes. The antennas will be made with polymer aerogel as a substrate to both reduce weight and improve performance, as demonstrated in an Aero Seedling. In addition, designing the antennas to be conformal to the aircraft fuselage will reduce drag.

  17. Structural Stability Of Detached Low Crested Breakwaters

    DEFF Research Database (Denmark)

    Burcharth, Hans F.; Kramer, Morten; Lamberti, Alberto

    2006-01-01

    The aim of the paper is to describe hydraulic stability of rock-armoured low-crested structures on the basis of new experimental tests and prototype observations. Rock armour stability results from earlier model tests under non-depth-limited long-crested head-on waves are reviewed. Results from new...... determining armour stone size in shallow water conditions is given together with a rule of thumb for the required stone size in depth-limited design waves. Rock toe stability is discussed on the basis of prototype experience, hard bottom 2-D tests in depth-limited waves and an existing hydraulic stability...... formula. Toe damage predicted by the formula is in agreement with experimental results. In field sites, damage at the toe induced by scour or by sinking is observed and the volume of the berm is often insufficient to avoid regressive erosion of the armour layer. Stone sinking and settlement in selected...

  18. Structural stability of nonlinear population dynamics.

    Science.gov (United States)

    Cenci, Simone; Saavedra, Serguei

    2018-01-01

    In population dynamics, the concept of structural stability has been used to quantify the tolerance of a system to environmental perturbations. Yet, measuring the structural stability of nonlinear dynamical systems remains a challenging task. Focusing on the classic Lotka-Volterra dynamics, because of the linearity of the functional response, it has been possible to measure the conditions compatible with a structurally stable system. However, the functional response of biological communities is not always well approximated by deterministic linear functions. Thus, it is unclear the extent to which this linear approach can be generalized to other population dynamics models. Here, we show that the same approach used to investigate the classic Lotka-Volterra dynamics, which is called the structural approach, can be applied to a much larger class of nonlinear models. This class covers a large number of nonlinear functional responses that have been intensively investigated both theoretically and experimentally. We also investigate the applicability of the structural approach to stochastic dynamical systems and we provide a measure of structural stability for finite populations. Overall, we show that the structural approach can provide reliable and tractable information about the qualitative behavior of many nonlinear dynamical systems.

  19. Structural stability of nonlinear population dynamics

    Science.gov (United States)

    Cenci, Simone; Saavedra, Serguei

    2018-01-01

    In population dynamics, the concept of structural stability has been used to quantify the tolerance of a system to environmental perturbations. Yet, measuring the structural stability of nonlinear dynamical systems remains a challenging task. Focusing on the classic Lotka-Volterra dynamics, because of the linearity of the functional response, it has been possible to measure the conditions compatible with a structurally stable system. However, the functional response of biological communities is not always well approximated by deterministic linear functions. Thus, it is unclear the extent to which this linear approach can be generalized to other population dynamics models. Here, we show that the same approach used to investigate the classic Lotka-Volterra dynamics, which is called the structural approach, can be applied to a much larger class of nonlinear models. This class covers a large number of nonlinear functional responses that have been intensively investigated both theoretically and experimentally. We also investigate the applicability of the structural approach to stochastic dynamical systems and we provide a measure of structural stability for finite populations. Overall, we show that the structural approach can provide reliable and tractable information about the qualitative behavior of many nonlinear dynamical systems.

  20. Attractor Structures of Signaling Networks: Consequences of Different Conformational Barcode Dynamics and Their Relations to Network-Based Drug Design.

    Science.gov (United States)

    Szalay, Kristóf Z; Nussinov, Ruth; Csermely, Peter

    2014-06-01

    Conformational barcodes tag functional sites of proteins and are decoded by interacting molecules transmitting the incoming signal. Conformational barcodes are modified by all co-occurring allosteric events induced by post-translational modifications, pathogen, drug binding, etc. We argue that fuzziness (plasticity) of conformational barcodes may be increased by disordered protein structures, by integrative plasticity of multi-phosphorylation events, by increased intracellular water content (decreased molecular crowding) and by increased action of molecular chaperones. This leads to increased plasticity of signaling and cellular networks. Increased plasticity is both substantiated by and inducing an increased noise level. Using the versatile network dynamics tool, Turbine (www.turbine.linkgroup.hu), here we show that the 10 % noise level expected in cellular systems shifts a cancer-related signaling network of human cells from its proliferative attractors to its largest, apoptotic attractor representing their health-preserving response in the carcinogen containing and tumor suppressor deficient environment modeled in our study. Thus, fuzzy conformational barcodes may not only make the cellular system more plastic, and therefore more adaptable, but may also stabilize the complex system allowing better access to its largest attractor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Stabilization and structural adjustment in Mozambique

    DEFF Research Database (Denmark)

    Tarp, Finn; Arndt, Channing; Jensen, Henning Tarp

    2000-01-01

    This paper outlines the complex historical legacy and structural adjustment efforts in Mozambique in addition to reviewing recent economic developments. An in-depth analysis of new and more reliable national accounts data show that macroeconomic stabilization has occurred through recovery from...

  2. Energetically Unfavorable Amide Conformations for N6-Acetyllysine Side Chains in Refined Protein Structures

    Science.gov (United States)

    Genshaft, Alexander; Moser, Joe-Ann S.; D'Antonio, Edward L.; Bowman, Christine M.; Christianson, David W.

    2013-01-01

    The reversible acetylation of lysine to form N6-acetyllysine in the regulation of protein function is a hallmark of epigenetics. Acetylation of the positively charged amino group of the lysine side chain generates a neutral N-alkylacetamide moiety that serves as a molecular “switch” for the modulation of protein function and protein-protein interactions. We now report the analysis of 381 N6-acetyllysine side chain amide conformations as found in 79 protein crystal structures and 11 protein NMR structures deposited in the Protein Data Bank (PDB) of the Research Collaboratory for Structural Bioinformatics. We find that only 74.3% of N6-acetyllysine residues in protein crystal structures and 46.5% in protein NMR structures contain amide groups with energetically preferred trans or generously trans conformations. Surprisingly, 17.6% of N6-acetyllysine residues in protein crystal structures and 5.3% in protein NMR structures contain amide groups with energetically unfavorable cis or generously cis conformations. Even more surprisingly, 8.1% of N6-acetyllysine residues in protein crystal structures and 48.2% in NMR structures contain amide groups with energetically prohibitive twisted conformations that approach the transition state structure for cis-trans isomerization. In contrast, 109 unique N-alkylacetamide groups contained in 84 highly-accurate small molecule crystal structures retrieved from the Cambridge Structural Database exclusively adopt energetically preferred trans conformations. Therefore, we conclude that cis and twisted N6-acetyllysine amides in protein structures deposited in the PDB are erroneously modeled due to their energetically unfavorable or prohibitive conformations. PMID:23401043

  3. Enrichment of Druggable Conformations from Apo Protein Structures Using Cosolvent-Accelerated Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Andrew Kalenkiewicz

    2015-04-01

    Full Text Available Here we describe the development of an improved workflow for utilizing experimental and simulated protein conformations in the structure-based design of inhibitors for anti-apoptotic Bcl-2 family proteins. Traditional structure-based approaches on similar targets are often constrained by the sparsity of available structures and difficulties in finding lead compounds that dock against flat, flexible protein-protein interaction surfaces. By employing computational docking of known small molecule inhibitors, we have demonstrated that structural ensembles derived from either accelerated MD (aMD or MD in the presence of an organic cosolvent generally give better scores than those assessed from analogous conventional MD. Furthermore, conformations obtained from combined cosolvent aMD simulations started with the apo-Bcl-xL structure yielded better average and minimum docking scores for known binders than an ensemble of 72 experimental apo- and ligand-bound Bcl-xL structures. A detailed analysis of the simulated conformations indicates that the aMD effectively enhanced conformational sampling of the flexible helices flanking the main Bcl-xL binding groove, permitting the cosolvent acting as small ligands to penetrate more deeply into the binding pocket and shape ligand-bound conformations not evident in conventional simulations. We believe this approach could be useful for identifying inhibitors against other protein-protein interaction systems involving highly flexible binding sites, particularly for targets with less accumulated structural data.

  4. Structural Stability of Low-Crested Breakwaters

    DEFF Research Database (Denmark)

    Kramer, Morten

    equations. New improved design formulae for calculation of static stability of LCS's are developed on the basis of new 2D and 3D laboratory experiments with scale models. The formulae are specially designed for breakwaters subject to shallow water waves and/or depth limited waves, as the majority...... of existing LCS’s are exposed to such conditions. The formulae are validated against prototype experience. Ecological aspects in relation to structural stability are important, and design guidance on how to consider ecology in the design is therefore given. The new design guidance adds practical and helpful...

  5. A user-friendly web portal for analyzing conformational changes in structures of Mycobacterium tuberculosis.

    Science.gov (United States)

    Hassan, Sameer; Thangam, Manonanthini; Vasudevan, Praveen; Kumar, G Ramesh; Unni, Rahul; Devi, P K Gayathri; Hanna, Luke Elizabeth

    2015-10-01

    Initiation of the Tuberculosis Structural Consortium has resulted in the expansion of the Mycobacterium tuberculosis (MTB) protein structural database. Currently, 969 experimentally solved structures are available for 354 MTB proteins. This includes multiple crystal structures for a given protein under different functional conditions, such as the presence of different ligands or mutations. In depth analysis of the multiple structures reveal that subtle differences exist in conformations of a given protein under varied conditions. Therefore, it is immensely important to understand the conformational differences between the multiple structures of a given protein in order to select the most suitable structure for molecular docking and structure-based drug designing. Here, we introduce a web portal ( http://bmi.icmr.org.in/mtbsd/torsion.php ) that we developed to provide comparative data on the ensemble of available structures of MTB proteins, such as Cα root means square deviation (RMSD), sequence identity, presence of mutations and torsion angles. Additionally, torsion angles were used to perform principal component analysis (PCA) to identify the conformational differences between the structures. Additionally, we present a few case studies to demonstrate this database. Graphical Abstract Conformational changes seen in the structures of the enoyl-ACP reductase protein encoded by the Mycobacterial gene inhA.

  6. 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

  7. 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

  8. Effects of high pressure homogenization on the activity, stability, kinetics and three-dimensional conformation of a glucose oxidase produced by Aspergillus niger.

    Directory of Open Access Journals (Sweden)

    Alline Artigiani Lima Tribst

    Full Text Available High pressure homogenization (HPH is a non-thermal method, which has been employed to change the activity and stability of biotechnologically relevant enzymes. This work investigated how HPH affects the structural and functional characteristics of a glucose oxidase (GO from Aspergillus niger. The enzyme was homogenized at 75 and 150 MPa and the effects were evaluated with respect to the enzyme activity, stability, kinetic parameters and molecular structure. The enzyme showed a pH-dependent response to the HPH treatment, with reduction or maintenance of activity at pH 4.5-6.0 and a remarkable activity increase (30-300% at pH 6.5 in all tested temperatures (15, 50 and 75°C. The enzyme thermal tolerance was reduced due to HPH treatment and the storage for 24 h at high temperatures (50 and 75°C also caused a reduction of activity. Interestingly, at lower temperatures (15°C the activity levels were slightly higher than that observed for native enzyme or at least maintained. These effects of HPH treatment on function and stability of GO were further investigated by spectroscopic methods. Both fluorescence and circular dichroism revealed conformational changes in the molecular structure of the enzyme that might be associated with the distinct functional and stability behavior of GO.

  9. Structure of Human Pancreatic Lipase-Related Protein 2 with the Lid in an Open Conformation

    Energy Technology Data Exchange (ETDEWEB)

    Eydoux, Cecilia; Spinelli, Silvia; Davis, Tara L.; Walker, John R.; Seitova, Alma; Dhe-Paganon, Sirano; De Caro, Alain; Cambillau, Christian; Carriere, Frederic (CNRS-UMR); (Toronto)

    2008-10-02

    Access to the active site of pancreatic lipase (PL) is controlled by a surface loop, the lid, which normally undergoes conformational changes only upon addition of lipids or amphiphiles. Structures of PL with their lids in the open and functional conformation have required cocrystallization with amphiphiles. Here we report two crystal structures of wild-type and unglycosylated human pancreatic lipase-related protein 2 (HPLRP2) with the lid in an open conformation in the absence of amphiphiles. These structures solved independently are strikingly similar, with some residues of the lid being poorly defined in the electron-density map. The open conformation of the lid is however different from that previously observed in classical liganded PL, suggesting different kinetic properties for HPLRP2. Here we show that the HPLRP2 is directly inhibited by E600, does not present interfacial activation, and acts preferentially on substrates forming monomers or small aggregates (micelles) dispersed in solution like monoglycerides, phospholipids and galactolipids, whereas classical PL displays reverse properties and a high specificity for unsoluble substrates like triglycerides and diglycerides forming oil-in-water interfaces. These biochemical properties imply that the lid of HPLRP2 is likely to spontaneously adopt in solution the open conformation observed in the crystal structure. This open conformation generates a large cavity capable of accommodating the digalactose polar head of galactolipids, similar to that previously observed in the active site of the guinea pig PLRP2, but absent from the classical PL. Most of the structural and kinetic properties of HPLRP2 were found to be different from those of rat PLRP2, the structure of which was previously obtained with the lid in a closed conformation. Our findings illustrate the essential role of the lid in determining the substrate specificity and the mechanism of action of lipases.

  10. A disulfide-stabilized conformer of methionine synthase reveals an unexpected role for the histidine ligand of the cobalamin cofactor

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Supratim; Koutmos, Markos; Pattridge, Katherine A.; Ludwig, Martha L.; Matthews, Rowena G. (Michigan)

    2008-07-08

    B{sub 12}-dependent methionine synthase (MetH) from Escherichia coli is a large modular protein that is alternately methylated by methyltetrahydrofolate to form methylcobalamin and demethylated by homocysteine to form cob(I)alamin. Major domain rearrangements are required to allow cobalamin to react with three different substrates: homocysteine, methyltetrahydrofolate, and S-adenosyl-l-methionine (AdoMet). These same rearrangements appear to preclude crystallization of the wild-type enzyme. Disulfide cross-linking was used to lock a C-terminal fragment of the enzyme into a unique conformation. Cysteine point mutations were introduced at Ile-690 and Gly-743. These cysteine residues span the cap and the cobalamin-binding module and form a cross-link that reduces the conformational space accessed by the enzyme, facilitating protein crystallization. Here, we describe an x-ray structure of the mutant fragment in the reactivation conformation; this conformation enables the transfer of a methyl group from AdoMet to the cobalamin cofactor. In the structure, the axial ligand to the cobalamin, His-759, dissociates from the cobalamin and forms intermodular contacts with residues in the AdoMet-binding module. This unanticipated intermodular interaction is expected to play a major role in controlling the distribution of conformers required for the catalytic and the reactivation cycles of the enzyme.

  11. Conformal maps and group contractions in nuclear structure

    International Nuclear Information System (INIS)

    Bonatsos, D.

    2011-01-01

    In mathematics, a conformal map is a function which preserves angles. We show how this procedure can be used in the framework of the Bohr Hamiltonian, leading to a Hamiltonian in a curved space, in which the mass depends on the nuclear deformation β, while it remains independent of the collective variable γ and the three Euler angles. This Hamiltonian is proved to be equivalent to that obtained using techniques of Supersymmetric Quantum Mechanics. Group contraction is a procedure in which a symmetry group is reduced into a group of lower symmetry in a certain limiting case. Examples are provided in the large boson number limit of the Interacting Boson Approximation (IBA) model by a) the contraction of the SU(3) algebra into the [R 5 ]SO(3) algebra of the rigid rotator, consisting of the angular momentum operators forming SO(3), plus 5 mutually commuting quantities, the quadrupole operators, b) the contraction of the O(6) algebra into the [R 5 ]SO(5) algebra of the γ-unstable rotator. We show how contractions can be used for constructing symmetry lines in the interior of the symmetry triangle of the IBA model. (author)

  12. Unifying dynamical and structural stability of equilibria

    Science.gov (United States)

    Arnoldi, Jean-François; Haegeman, Bart

    2016-09-01

    We exhibit a fundamental relationship between measures of dynamical and structural stability of linear dynamical systems-e.g. linearized models in the vicinity of equilibria. We show that dynamical stability, quantified via the response to external perturbations (i.e. perturbation of dynamical variables), coincides with the minimal internal perturbation (i.e. perturbations of interactions between variables) able to render the system unstable. First, by reformulating a result of control theory, we explain that harmonic external perturbations reflect the spectral sensitivity of the Jacobian matrix at the equilibrium, with respect to constant changes of its coefficients. However, for this equivalence to hold, imaginary changes of the Jacobian's coefficients have to be allowed. The connection with dynamical stability is thus lost for real dynamical systems. We show that this issue can be avoided, thus recovering the fundamental link between dynamical and structural stability, by considering stochastic noise as external and internal perturbations. More precisely, we demonstrate that a linear system's response to white-noise perturbations directly reflects the intensity of internal white-noise disturbance that it can accommodate before becoming stochastically unstable.

  13. Evaluation of the Structure Stability of a Plate Girder Bridge Using MIDAS Structure Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eui Soo; Kim, Jong Hyuk [National Forensic Service, Wonju (Korea, Republic of)

    2014-04-15

    Recently, as a means of resolving the issue of legal liability in the event of an accident or a disaster, a wide variety of simulation techniques, such as structural and structure-fluid interaction analysis, have been used in the field of forensic engineering. The plate girder bridge discussed in this paper was being constructed between a pier and an abutment to expand an existing bridge, but an accident whereby the bridge overturned occurred at the end of the concrete laying process for a protective wall. This accident was caused by additional loads not being considered at the time of the design as well as the actual construction being different from the design. The additional loads ultimately generated a negative support force. In this study, we determined the cause of the accident by comparing the structural stability of the original design with that of the additional, non-conforming construction using MIDAS structural analysis.

  14. Evaluation of the Structure Stability of a Plate Girder Bridge Using MIDAS Structure Analysis

    International Nuclear Information System (INIS)

    Kim, Eui Soo; Kim, Jong Hyuk

    2014-01-01

    Recently, as a means of resolving the issue of legal liability in the event of an accident or a disaster, a wide variety of simulation techniques, such as structural and structure-fluid interaction analysis, have been used in the field of forensic engineering. The plate girder bridge discussed in this paper was being constructed between a pier and an abutment to expand an existing bridge, but an accident whereby the bridge overturned occurred at the end of the concrete laying process for a protective wall. This accident was caused by additional loads not being considered at the time of the design as well as the actual construction being different from the design. The additional loads ultimately generated a negative support force. In this study, we determined the cause of the accident by comparing the structural stability of the original design with that of the additional, non-conforming construction using MIDAS structural analysis

  15. Conformational states of N-acylalanine dithio esters: correlation of resonance Raman spectra with structures

    International Nuclear Information System (INIS)

    Lee, H.; Angus, R.H.; Storer, A.C.; Varughese, K.I.; Carey, P.R.

    1988-01-01

    The conformational states of N-acylalanine dithio esters, involving rotational isomers about the RC(=O)NH-CH(CH 3 ) and NHCH(CH 3 )-C(=S) bonds, are defined and compared to those of N-acylglycine dithio esters. The structure of N-(p-nitrobenzoyl)-DL-alanine ethyl dithio ester has been determined by X-ray crystallographic analysis; it is a B-type conformer with the amide N atom cis to the thiol sulfur. Raman and resonance Raman (RR) measurements on this compound and for the B conformers of solid N-benzoyl-DL-alanine ethyl dithio ester and N-(β-phenylpropionyl)-DL-alanine ethyl dithio ester and its NHCH(CD 3 )C(=S) and NHCH(CH 3 ) 13 C(=S) analogues are used to set up a library of RR data for alanine-based dithio esters in a B-conformer state. RR data for this solid material in its isotopically unsubstituted and CH(C-D 3 )C(=S) and CH(CH 3 ) 13 C(=S) forms provide information on the RR signatures of alanine dithio esters in A-like conformations. RR spectra are compared for the solid compounds, for N-(p-nitrobenzoyl)-DL-alanine, N-(β-phenylpropionyl)-DL-alanine, and (methyloxycarbonyl)-L-phenylalanyl-DL-alanine ethyl dithio ester, and for several 13 C=S- and CD 3 -substituted analogues in CCl 4 or aqueous solutions. The RR data demonstrate that the alanine-based dithio esters take up A, B, and C 5 conformations in solution. The RR spectra of these conformers are clearly distinguishable from those for the same conformers of N-acylglycine dithio esters. However, the crystallographic and spectroscopic results show that the results show that the conformational properties of N-acylglycine and N-acylalanine dithio esters are very similar

  16. Mutation of the His ligand in mitoNEET stabilizes the 2Fe–2S cluster despite conformational heterogeneity in the ligand environment

    Energy Technology Data Exchange (ETDEWEB)

    Conlan, Andrea R.; Paddock, Mark L.; Homer, Christina [University of California at San Diego, La Jolla, CA 92093 (United States); Axelrod, Herbert L.; Cohen, Aina E. [Stanford Synchrotron Radiation Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Abresch, Edward C.; Zuris, John A. [University of California at San Diego, La Jolla, CA 92093 (United States); Nechushtai, Rachel [Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904 (Israel); Jennings, Patricia A., E-mail: pajennin@ucsd.edu [University of California at San Diego, La Jolla, CA 92093 (United States)

    2011-06-01

    The spectroscopic and stability properties and X-ray crystal structure of the H87C mutant of the 2Fe–2S ligand mitoNEET are reported. Strikingly, the single point mutation leads to changes in its absorbance and CD spectra and an increase of around sixfold in the stability of the 2Fe–2S clusters over the pH range 5–7. However, the crystal structure of the H87C mutant displays heterogeneity in a few key residues, including the introduced cysteine ligand. Nonetheless, the cluster is highly stabilized from release. MitoNEET is the only identified Fe–S protein localized to the outer mitochondrial membrane and a 1.5 Å resolution X-ray analysis has revealed a unique structure [Paddock et al. (2007 ▶), Proc. Natl Acad. Sci. USA, 104, 14342–14347]. The 2Fe–2S cluster is bound with a 3Cys–1His coordination which defines a new class of 2Fe–2S proteins. The hallmark feature of this class is the single noncysteine ligand His87, which when replaced by Cys decreases the redox potential (E{sub m}) by ∼300 mV and increases the stability of the cluster by around sixfold. Unexpectedly, the pH dependence of the lifetime of the 2Fe–2S cluster remains the same as in the wild-type protein. Here, the crystal structure of H87C mitoNEET was determined to 1.7 Å resolution (R factor = 18%) to investigate the structural basis of the changes in the properties of the 2Fe–2S cluster. In comparison to the wild type, structural changes are localized to the immediate vicinity of the cluster-binding region. Despite the increased stability, Cys87 displays two distinct conformations, with distances of 2.3 and 3.2 Å between the S{sup γ} and the outer Fe of the 2Fe–2S cluster. In addition, Lys55 exhibits multiple conformations in the H87C mutant protein. The structure and distinct characteristics of the H87C mutant provide a framework for further studies investigating the effects of mutation on the properties of the 2Fe–2S cluster in this new class of proteins.

  17. Structural Stability of Tokamak Equilibrium: Transport Barriers

    Energy Technology Data Exchange (ETDEWEB)

    Solano, E. R.

    2001-07-01

    A generalised theory of structural stability of differential equations is introduced and applied to the Grad-Shafranov equation. It is discussed how the formation and loss of transport barrier could be associated with the appearance/disappearance of equilibria. The equilibrium conjecture is presented: transport barriers are associated with locally diamagnetic regions in the plasma, and affected by the paramagnetism of the bootstrap current. (Author) 18 refs.

  18. A novel mechanism for antiglycative action of limonene through stabilization of protein conformation.

    Science.gov (United States)

    Joglekar, Madhav M; Panaskar, Shrimant N; Chougale, Ashok D; Kulkarni, Mahesh J; Arvindekar, Akalpita U

    2013-10-01

    Inhibition of protein glycation is known to ameliorate secondary complications in diabetes. In the present study antiglycative properties of limonene, a natural product, were evaluated using BSA as a model protein. AMG (aminoguanidine) was used as a positive control. Measurement of total AGEs (Advanced Glycation End-products) and specific AGEs revealed that limonene could inhibit protein glycation to the extent of 56.3% and 75.1% respectively at 50 μM concentration as against 54.4% and 82.2% by AMG at 1 mM. Congo red binding and CD (Circular Dichroism) analysis revealed inhibition of α-helix to β-sheet transition wherein 18.5% β-sheet structures were observed in glycated BSA (bovine serum albumin) as against 4.9% with limonene. Glycation of protein in the presence of urea was enhanced by 18%, while in the presence of limonene it was reduced by 23% revealing the stabilizing effect of limonene. Electrophoretic mobility was similar to the normal control and a zeta potential value of -12.1 mV as against -15.1 mV in diabetic control was observed. Inhibition of glycation in limonene treated samples was confirmed through LC-MS analysis wherein AGEs such as pentosidine, CML (N(ε)-(carboxymethyl)lysine), CEL (N(ε)-(carboxyethyl)lysine), MOLD (methylglyoxal-lysine dimer) and imidazolone observed in glycated samples were absent in limonene treated samples. PatchDock studies revealed that limonene could bind to the major glycation sites IB, IIA and IIB sub domains and AMG to the IIIA sub domain. Thus limonene is a potent protein glycation inhibitor that prevents protein glycation through a novel mechanism of stabilization of protein structure through hydrophobic interactions.

  19. Osserman and conformally Osserman manifolds with warped and twisted product structure

    OpenAIRE

    Brozos-Vazquez, M.; Garcia-Rio, E.; Vazquez-Lorenzo, R.

    2008-01-01

    We characterize Osserman and conformally Osserman Riemannian manifolds with the local structure of a warped product. By means of this approach we analyze the twisted product structure and obtain, as a consequence, that the only Osserman manifolds which can be written as a twisted product are those of constant curvature.

  20. Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

    International Nuclear Information System (INIS)

    Eibl, Clarissa; Hessenberger, Manuel; Wenger, Julia; Brandstetter, Hans

    2014-01-01

    Pyrin domains (PYDs) recruit downstream effector molecules in NLR signalling. A specific charge-relay system suggests a the formation of a signalling complex involving a PYD dimer. The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed

  1. Guiding exploration in conformational feature space with Lipschitz underestimation for ab-initio protein structure prediction.

    Science.gov (United States)

    Hao, Xiaohu; Zhang, Guijun; Zhou, Xiaogen

    2018-04-01

    Computing conformations which are essential to associate structural and functional information with gene sequences, is challenging due to the high dimensionality and rugged energy surface of the protein conformational space. Consequently, the dimension of the protein conformational space should be reduced to a proper level, and an effective exploring algorithm should be proposed. In this paper, a plug-in method for guiding exploration in conformational feature space with Lipschitz underestimation (LUE) for ab-initio protein structure prediction is proposed. The conformational space is converted into ultrafast shape recognition (USR) feature space firstly. Based on the USR feature space, the conformational space can be further converted into Underestimation space according to Lipschitz estimation theory for guiding exploration. As a consequence of the use of underestimation model, the tight lower bound estimate information can be used for exploration guidance, the invalid sampling areas can be eliminated in advance, and the number of energy function evaluations can be reduced. The proposed method provides a novel technique to solve the exploring problem of protein conformational space. LUE is applied to differential evolution (DE) algorithm, and metropolis Monte Carlo(MMC) algorithm which is available in the Rosetta; When LUE is applied to DE and MMC, it will be screened by the underestimation method prior to energy calculation and selection. Further, LUE is compared with DE and MMC by testing on 15 small-to-medium structurally diverse proteins. Test results show that near-native protein structures with higher accuracy can be obtained more rapidly and efficiently with the use of LUE. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Conformational aspects of dibenzo-tetroxecin: A structural, Raman spectroscopic and computational study

    Science.gov (United States)

    Gordon, Keith C.; McAdam, C. John; Moratti, Stephen C.; Shillito, Georgina E.; Simpson, Jim

    2017-10-01

    Crystalline dibenzo-tetroxecin (I) has been prepared from a reaction between catechol and dichloromethane and its molecular and crystal structure, together with the Raman spectrum of the material in the solid state and in solution, is reported. The molecular structure shows the molecule adopts an anti or stepped conformation. Density functional theory (DFT) optimisation and frequency calculations using the B3LYP functional with the 6-31G(d) basis set showed the presence of syn- and anti-conformers of (I), with the anti-conformer predicted to be the lower in energy by 13.6 kJ mol-1. The vibrational frequencies and relative Raman intensities of the anti-conformer are well modelled by the DFT calculations. The bond lengths and angles obtained for the anti-conformer are also in good agreement with the crystal structure. The crystal structure of (I) is stabilised by intermolecular Csbnd H⋯O hydrogen bonds that generate a three dimensional network.

  3. Insights into the role of hydration in protein structure and stability obtained through hydrostatic pressure studies

    Directory of Open Access Journals (Sweden)

    C.A. Royer

    2005-08-01

    Full Text Available A thorough understanding of protein structure and stability requires that we elucidate the molecular basis for the effects of both temperature and pressure on protein conformational transitions. While temperature effects are relatively well understood and the change in heat capacity upon unfolding has been reasonably well parameterized, the state of understanding of pressure effects is much less advanced. Ultimately, a quantitative parameterization of the volume changes (at the basis of pressure effects accompanying protein conformational transitions will be required. The present report introduces a qualitative hypothesis based on available model compound data for the molecular basis of volume change upon protein unfolding and its dependence on temperature.

  4. Conforming to interface structured adaptive mesh refinement: 3D algorithm and implementation

    Science.gov (United States)

    Nagarajan, Anand; Soghrati, Soheil

    2018-03-01

    A new non-iterative mesh generation algorithm named conforming to interface structured adaptive mesh refinement (CISAMR) is introduced for creating 3D finite element models of problems with complex geometries. CISAMR transforms a structured mesh composed of tetrahedral elements into a conforming mesh with low element aspect ratios. The construction of the mesh begins with the structured adaptive mesh refinement of elements in the vicinity of material interfaces. An r-adaptivity algorithm is then employed to relocate selected nodes of nonconforming elements, followed by face-swapping a small fraction of them to eliminate tetrahedrons with high aspect ratios. The final conforming mesh is constructed by sub-tetrahedralizing remaining nonconforming elements, as well as tetrahedrons with hanging nodes. In addition to studying the convergence and analyzing element-wise errors in meshes generated using CISAMR, several example problems are presented to show the ability of this method for modeling 3D problems with intricate morphologies.

  5. The Role of Molecular Structure and Conformation in Polymer Electronics

    NARCIS (Netherlands)

    von Hauff, Elizabeth

    2011-01-01

    ABSTRACT Conjugated polymers have unique material properties that make them promising for a wide range of applications. The potential lies in the virtually infinite possibilities for creating new materials for specific applications by simply chemically tuning the molecular structure. Conjugated

  6. Spectroscopic Diagnosis of Excited-State Aromaticity: Capturing Electronic Structures and Conformations upon Aromaticity Reversal.

    Science.gov (United States)

    Oh, Juwon; Sung, Young Mo; Hong, Yongseok; Kim, Dongho

    2018-03-06

    scrutinize this intriguing and challenging scientific issue, expanded porphyrins have been utilized as the ideal testing platform for investigating aromaticity because they show distinct aromatic and antiaromatic characters with aromaticity-specific spectroscopic features. Expanded porphyrins exhibit perfect aromatic and antiaromatic congener pairs having the same molecular framework but different numbers of π electrons, which facilitates the study of the pure effect of aromaticity by comparative analyses. On the basis of the characteristics of expanded porphyrins, time-resolved electronic and vibrational absorption spectroscopies capture the changes in electronic structure and molecular conformations driven by the change in aromaticity and provide clear evidence for aromaticity reversal in the excited states. The approaches described in this Account pave the way for the development of new and alternative experimental indices for the evaluation of excited-state aromaticity, which will enable overarching and fundamental comprehension of the role of (anti)aromaticity in the stability, dynamics, and reactivity in the excited states with possible implications for practical applications.

  7. De novo protein structure prediction by dynamic fragment assembly and conformational space annealing.

    Science.gov (United States)

    Lee, Juyong; Lee, Jinhyuk; Sasaki, Takeshi N; Sasai, Masaki; Seok, Chaok; Lee, Jooyoung

    2011-08-01

    Ab initio protein structure prediction is a challenging problem that requires both an accurate energetic representation of a protein structure and an efficient conformational sampling method for successful protein modeling. In this article, we present an ab initio structure prediction method which combines a recently suggested novel way of fragment assembly, dynamic fragment assembly (DFA) and conformational space annealing (CSA) algorithm. In DFA, model structures are scored by continuous functions constructed based on short- and long-range structural restraint information from a fragment library. Here, DFA is represented by the full-atom model by CHARMM with the addition of the empirical potential of DFIRE. The relative contributions between various energy terms are optimized using linear programming. The conformational sampling was carried out with CSA algorithm, which can find low energy conformations more efficiently than simulated annealing used in the existing DFA study. The newly introduced DFA energy function and CSA sampling algorithm are implemented into CHARMM. Test results on 30 small single-domain proteins and 13 template-free modeling targets of the 8th Critical Assessment of protein Structure Prediction show that the current method provides comparable and complementary prediction results to existing top methods. Copyright © 2011 Wiley-Liss, Inc.

  8. Counterion-Induced Inversion of Conformer Stability of a [5]Helquat Dication

    Czech Academy of Sciences Publication Activity Database

    Severa, Lukáš; Jirásek, Michael; Švec, Pavel; Teplý, Filip; Révész, Agnes; Schröder, Detlef; Koval, Dušan; Kašička, Václav; Císařová, I.; Šaman, David

    2012-01-01

    Roč. 77, č. 8 (2012), s. 624-635 ISSN 2192-6506 R&D Projects: GA ČR GAP207/10/2391; GA ČR(CZ) GA203/08/1428 Institutional research plan: CEZ:AV0Z40550506 Keywords : conformers * density functional calculations * dications * helical molecules * ion pairs * mass spectrometry Subject RIV: CC - Organic Chemistry

  9. Structure and conformational dynamics of scaffolded DNA origami nanoparticles

    Science.gov (United States)

    2017-05-08

    vertices of the tetrahedron, and an unconstrained 4-arm vertex region corresponding to the vertices of the octahe- dron (Figure 2B and C). Both the 3...all-atommodels of the tetrahe- dron , octahedron, unconstrained 3- and 4-arm vertices, and the unconstrained duplex bulge represent equilibrium val...structural analysis of 4-arm vertices within a self-assembled octahe- dron imaged using cryo-EM (87). This prediction suggests an enantiomeric preference

  10. Chain conformations of ABA triblock coplymers in microphase-separated structures for SANS

    International Nuclear Information System (INIS)

    Matsushita, Y.; Nomura, M.; Watanabe, J.; Mogi, Y.; Noda, I.; Han, C.C.

    1993-01-01

    Single chain conformations of center block, polystyrene, of poly(2-vinylpyridine-b-styrene-b-2-vinylpyridine)(PSP) triblock copolymers of the ABA type in bulk were measured by small angle neutron scattering (SANS), while microphase separation structures were studied by small angle X-ray Scattering (SAXS) and transmission electron microscopy (TEM). From the morphological observations, PSP block copolymers have confirmed to have alternating lamellar structure both when φs = 0.33 and φs = 0.5, where φs is the volume fraction of polystyrene blocks. It was also clarified that the chain dimension of center blocks of sample with φs = 0.33 is smaller than that of sample with φs = 0.5. This result may mean that the center blocks have bridge-righ conformation when φs = 0.33 while they have loop-rich conformation when φs = 0.5. (author)

  11. Nucleotide-induced conformational dynamics in ABC transporters from structure-based coarse grained modelling.

    Science.gov (United States)

    Flechsig, Holger

    2016-02-01

    ATP-binding cassette (ABC) transporters are integral membrane proteins which mediate the exchange of diverse substrates across membranes powered by ATP molecules. Our understanding of their activity is still hampered since the conformational dynamics underlying the operation of such proteins cannot yet be resolved in detailed molecular dynamics studies. Here a coarse grained model which allows to mimic binding of nucleotides and follow subsequent conformational motions of full-length transporter structures in computer simulations is proposed and implemented. To justify its explanatory quality, the model is first applied to the maltose transporter system for which multiple conformations are known and we find that the model predictions agree remarkably well with the experimental data. For the MalK subunit the switching from open to the closed dimer configuration upon ATP binding is reproduced and, moreover, for the full-length maltose transporter, progression from inward-facing to the outward-facing state is correctly obtained. For the heme transporter HmuUV, for which only the free structure could yet be determined, the model was then applied to predict nucleotide-induced conformational motions. Upon binding of ATP-mimicking ligands the structure changed from a conformation in which the nucleotide-binding domains formed an open shape, to a conformation in which they were found in tight contact, while, at the same time, a pronounced rotation of the transmembrane domains was observed. This finding is supported by normal mode analysis, and, comparison with structural data of the homologous vitamin B12 transporter BtuCD suggests that the observed rotation mechanism may contribute a common functional aspect for this class of ABC transporters. Although in HmuuV noticeable rearrangement of essential transmembrane helices was detected, there are no indications from our simulations that ATP binding alone may facilitate propagation of substrate molecules in this transporter

  12. An in silico study of the molecular basis of B-RAF activation and conformational stability

    Directory of Open Access Journals (Sweden)

    Jónsdóttir Svava

    2009-07-01

    Full Text Available Abstract Background B-RAF kinase plays an important role both in tumour induction and maintenance in several cancers and it is an attractive new drug target. However, the structural basis of the B-RAF activation is still not well understood. Results In this study we suggest a novel molecular basis of B-RAF activation based on molecular dynamics (MD simulations of B-RAFWT and the B-RAFV600E, B-RAFK601E and B-RAFD594V mutants. A strong hydrogen bond network was identified in B-RAFWT in which the interactions between Lys601 and the well known catalytic residues Lys483, Glu501 and Asp594 play an important role. It was found that several mutations, which directly or indirectly destabilized the interactions between these residues within this network, contributed to the changes in B-RAF activity. Conclusion Our results showed that the above mechanisms lead to the disruption of the electrostatic interactions between the A-loop and the αC-helix in the activating mutants, which presumably contribute to the flipping of the activation segment to an active form. Conversely, in the B-RAFD594V mutant that has impaired kinase activity, and in B-RAFWT these interactions were strong and stabilized the kinase inactive form.

  13. An in silico study of the molecular basis of B-RAF activation and conformational stability

    DEFF Research Database (Denmark)

    Fratev, Filip Filipov; Jonsdottir, Svava Osk

    2009-01-01

    B-RAF kinase plays an important role both in tumour induction and maintenance in several cancers and it is an attractive new drug target. However, the structural basis of the B-RAF activation is still not well understood. RESULTS: In this study we suggest a novel molecular basis of B-RAF activation...... based on molecular dynamics (MD) simulations of B-RAFWT and the B-RAFV600E, B-RAFK601E and B-RAFD594V mutants. A strong hydrogen bond network was identified in B-RAFWT in which the interactions between Lys601 and the well known catalytic residues Lys483, Glu501 and Asp594 play an important role...... the A-loop and the alphaC-helix in the activating mutants, which presumably contribute to the flipping of the activation segment to an active form. Conversely, in the B-RAFD594V mutant that has impaired kinase activity, and in B-RAFWT these interactions were strong and stabilized the kinase inactive...

  14. Influence of functionalized nanoparticles on conformational stability of type I collagen for possible biomedical applications.

    Science.gov (United States)

    Kandamchira, Aswathy; Selvam, Sangeetha; Marimuthu, Nidhin; Janardhanan, Sreeram Kalarical; Fathima, Nishter Nishad

    2013-12-01

    Collagen-nanoparticle interactions are vital for many biomedical applications including drug delivery and tissue engineering applications. Iron oxide nanoparticles synthesized using starch template according to our earlier reported procedures were functionalized by treating them with Gum Arabic (GA), a biocompatible polysaccharide, so as to enhance the interaction between nanoparticle surfaces and collagen. Viscosity, circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) techniques have been used to study the collagen-nanoparticle interactions. The relative viscosity for collagen-nanoparticle conjugate was found to increase with increase in concentration of the nanoparticle within the concentration range investigated, which is due to the aggregation of protein onto the surface of nanoparticle. The CD spectra for the collagen-nanoparticle at different concentration ratios do not have much variation in the Rpn values (ratio of positive peak intensity over negative peak intensity) after functionalization with GA. The variation of molar ellipticity values for collagen-nanoparticle is due to the glycoprotein present in GA. The collagen triple helical structure is maintained after interaction with nanoparticles. The FTIR spectra of native collagen, Coll-Fs (nanoparticle without functionalization) and Coll-FsG (nanoparticle functionalized with GA) show clearly the amide I, II, III bands, with respect to collagen. The ability of polysaccharide stabilized/functionalized nanoparticles to maintain the collagen properties would help in its biomedical applications. © 2013.

  15. On the conformational stability of the smallest RNA kissing complexes maintained through two G·C base pairs

    International Nuclear Information System (INIS)

    Chu, Wally; Weerasekera, Akila; Kim, Chul-Hyun

    2017-01-01

    Two identical 5′GACG3′ tetra-loop motifs with different stem sequences (called H2 and H3) are found in the 5′ end region of Moloney Murine Leukemia Virus (MMLV) genomic RNA. They play important roles in RNA dimerization and encapsidation through two identical tetra-loops (5′GACG3′) forming a loop-to-loop kissing complex, the smallest RNA kissing complex ever found in nature. We examined the effects of a loop-closing base pair as well as a stem sequence on the conformational stability of the kissing complex. UV melting analysis and gel electrophoresis were performed on eight RNA sequences mimicking the H2 and H3 hairpin tetra-loops with variation in loop-closing base pairs. Our results show that changing the loop-closing base pair from the wildtype (5′A·U3′ for H3, 5′U·A3′ for H2) to 5′G·C3’/5′C·G3′ has significant effect on the stability of the kissing complexes: the substitution to 5′C·G3′ significantly decreases both thermal and mechanical stability, while switching to the 5′G·C3′ significantly increases the mechanical stability only. The kissing complexes with the wildtype loop-closing base pairs (5′A·U3′ for H3 and 5′U·A3′ for H2) show different stability when attached to a different stem sequence (H2 stem vs. H3 stem). This suggests that not only the loop-closing base pair itself, but also the stem sequence, affects the conformational stability of the RNA kissing complex. - Highlights: • Thermodynamic parameters of the smallest RNA kissing interactions were measured. • The effects of loop-closing base pairs on the RNA kissing complex was investigated. • Changing the base pair to 5′CG3′ decreases the stability of the kissing complex. • Changing it to 5′GC3′ increases the mechanical resilience of the kissing complex. • Difference in its stem sequence also affects the stability of the kissing complex.

  16. Conformational sampling in template-free protein loop structure modeling: an overview.

    Science.gov (United States)

    Li, Yaohang

    2013-01-01

    Accurately modeling protein loops is an important step to predict three-dimensional structures as well as to understand functions of many proteins. Because of their high flexibility, modeling the three-dimensional structures of loops is difficult and is usually treated as a "mini protein folding problem" under geometric constraints. In the past decade, there has been remarkable progress in template-free loop structure modeling due to advances of computational methods as well as stably increasing number of known structures available in PDB. This mini review provides an overview on the recent computational approaches for loop structure modeling. In particular, we focus on the approaches of sampling loop conformation space, which is a critical step to obtain high resolution models in template-free methods. We review the potential energy functions for loop modeling, loop buildup mechanisms to satisfy geometric constraints, and loop conformation sampling algorithms. The recent loop modeling results are also summarized.

  17. CONFORMATIONAL SAMPLING IN TEMPLATE-FREE PROTEIN LOOP STRUCTURE MODELING: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Yaohang Li

    2013-02-01

    Full Text Available Accurately modeling protein loops is an important step to predict three-dimensional structures as well as to understand functions of many proteins. Because of their high flexibility, modeling the three-dimensional structures of loops is difficult and is usually treated as a “mini protein folding problem” under geometric constraints. In the past decade, there has been remarkable progress in template-free loop structure modeling due to advances of computational methods as well as stably increasing number of known structures available in PDB. This mini review provides an overview on the recent computational approaches for loop structure modeling. In particular, we focus on the approaches of sampling loop conformation space, which is a critical step to obtain high resolution models in template-free methods. We review the potential energy functions for loop modeling, loop buildup mechanisms to satisfy geometric constraints, and loop conformation sampling algorithms. The recent loop modeling results are also summarized.

  18. Conformational locking by design: relating strain energy with luminescence and stability in rigid metal-organic frameworks.

    Science.gov (United States)

    Shustova, Natalia B; Cozzolino, Anthony F; Dincă, Mircea

    2012-12-05

    Minimization of the torsional barrier for phenyl ring flipping in a metal-organic framework (MOF) based on the new ethynyl-extended octacarboxylate ligand H(8)TDPEPE leads to a fluorescent material with a near-dark state. Immobilization of the ligand in the rigid structure also unexpectedly causes significant strain. We used DFT calculations to estimate the ligand strain energies in our and all other topologically related materials and correlated these with empirical structural descriptors to derive general rules for trapping molecules in high-energy conformations within MOFs. These studies portend possible applications of MOFs for studying fundamental concepts related to conformational locking and its effects on molecular reactivity and chromophore photophysics.

  19. Effects of nanorod structure and conformation of fatty acid self-assembled layers on superhydrophobicity of zinc oxide surface.

    Science.gov (United States)

    Badre, Chantal; Dubot, P; Lincot, Daniel; Pauporte, Thierry; Turmine, Mireille

    2007-12-15

    Superhydrophobic surfaces have been prepared from nanostructured zinc oxide layers by a treatment with fatty acid molecules. The layers are electrochemically deposited from an oxygenated aqueous zinc chloride solution. The effects of the layer's structure, from a dense film to that of a nanorod array, as well as that of the properties of the fatty acid molecules based on C18 chains are described. A contact angle (CA) as high as 167 degrees is obtained with the nanorod structure and the linear saturated molecule (stearic acid). Lower values are found with molecules having an unsaturated bond on C9, in particular with a cis conformation (140 degrees ). These results, supplemented by infrared spectroscopy, indicate an enhancement of the sensitivity to the properties of the fatty acid molecules (conformation, flexibility, saturated or not) when moving from the flat surface to the nanostructured surface. This is attributed to a specific influence of the structure of the tops of the rods and lateral wall properties on the adsorption and organization of the molecules. CA measurements show a very good stability of the surface in time if stored in an environment protected from UV radiations.

  20. Structural analysis of linear and conformational epitopes of allergens

    Science.gov (United States)

    Ivanciuc, Ovidiu; Schein, Catherine H.; Garcia, Tzintzuni; Oezguen, Numan; Negi, Surendra S.; Braun, Werner

    2009-01-01

    In many countries regulatory agencies have adopted safety guidelines, based on bioinformatics rules from the WHO/FAO and EFSA recommendations, to prevent potentially allergenic novel foods or agricultural products from reaching consumers. We created the Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/) to combine data that had previously been available only as flat files on Web pages or in the literature. SDAP was designed to be user friendly, to be of maximum use to regulatory agencies, clinicians, as well as to scientists interested in assessing the potential allergenic risk of a protein. We developed methods, unique to SDAP, to compare the physicochemical properties of discrete areas of allergenic proteins to known IgE epitopes. We developed a new similarity measure, the property distance (PD) value that can be used to detect related segments in allergens with clinical observed crossreactivity. We have now expanded this work to obtain experimental validation of the PD index as a quantitative predictor of IgE cross-reactivity, by designing peptide variants with predetermined PD scores relative to known IgE epitopes. In complementary work we show how sequence motifs characteristic of allergenic proteins in protein families can be used as fingerprints for allergenicity. PMID:19121639

  1. Comparative study of the conformational lock, dissociative thermal inactivation and stability of euphorbia latex and lentil seedling amine oxidases.

    Science.gov (United States)

    Amani, M; Moosavi-Movahedi, A A; Floris, G; Longu, S; Mura, A; Moosavi-Nejad, S Z; Saboury, A A; Ahmad, F

    2005-04-01

    The thermal stability of copper/quinone containing amine oxidases from Euphorbia characias latex (ELAO) and lentil seedlings (LSAO) was measured in 100 mM potassium phosphate buffer (pH 7.0) following changes in absorbance at 292 nm. ELAO was shown to be about 10 degrees C more stable than LSAO. The dissociative thermal inactivation of ELAO was studied using putrescine as substrate at different temperatures in the range 47-70 degrees C, and a "conformational lock" was developed using the theory pertaining to oligomeric enzyme. Moreover ELAO was shown to be more stable towards denaturants than LSAO, as confirmed by dodecyl trimethylammonium bromide denaturation curves. A comparison of the numbers of contact sites in inter-subunits of ELAO relative to LSAO led us to conclude that the higher stability of ELAO to temperature and towards denaturants was due to the presence of larger number of contact sites in the conformational lock of the enzyme. This study also gives a putative common mechanism for thermal inactivation of amine oxidases and explains the importance of C-terminal conserved amino acids residues in this class of enzymes.

  2. Microscopic silicon-based lateral high-aspect-ratio structures for thin film conformality analysis

    International Nuclear Information System (INIS)

    Gao, Feng; Arpiainen, Sanna; Puurunen, Riikka L.

    2015-01-01

    Film conformality is one of the major drivers for the interest in atomic layer deposition (ALD) processes. This work presents new silicon-based microscopic lateral high-aspect-ratio (LHAR) test structures for the analysis of the conformality of thin films deposited by ALD and by other chemical vapor deposition means. The microscopic LHAR structures consist of a lateral cavity inside silicon with a roof supported by pillars. The cavity length (e.g., 20–5000 μm) and cavity height (e.g., 200–1000 nm) can be varied, giving aspect ratios of, e.g., 20:1 to 25 000:1. Film conformality can be analyzed with the microscopic LHAR by several means, as demonstrated for the ALD Al 2 O 3 and TiO 2 processes from Me 3 Al/H 2 O and TiCl 4 /H 2 O. The microscopic LHAR test structures introduced in this work expose a new parameter space for thin film conformality investigations expected to prove useful in the development, tuning and modeling of ALD and other chemical vapor deposition processes

  3. A new topology for curved space--time which incorporates the causal, differential, and conformal structures

    International Nuclear Information System (INIS)

    Hawking, S.W.; King, A.R.; McCarthy, P.J.

    1976-01-01

    A new topology is proposed for strongly causal space--times. Unlike the standard manifold topology (which merely characterizes continuity properties), the new topology determines the causal, differential, and conformal structures of space--time. The topology is more appealing, physical, and manageable than the topology previously proposed by Zeeman for Minkowski space. It thus seems that many calculations involving the above structures may be made purely topological

  4. Drug Development in Conformational Diseases: A Novel Family of Chemical Chaperones that Bind and Stabilise Several Polymorphic Amyloid Structures.

    Directory of Open Access Journals (Sweden)

    Marquiza Sablón-Carrazana

    Full Text Available The increasing prevalence of conformational diseases, including Alzheimer's disease, type 2 Diabetes Mellitus and Cancer, poses a global challenge at many different levels. It has devastating effects on the sufferers as well as a tremendous economic impact on families and the health system. In this work, we apply a cross-functional approach that combines ideas, concepts and technologies from several disciplines in order to study, in silico and in vitro, the role of a novel chemical chaperones family (NCHCHF in processes of protein aggregation in conformational diseases. Given that Serum Albumin (SA is the most abundant protein in the blood of mammals, and Bovine Serum Albumin (BSA is an off-the-shelf protein available in most labs around the world, we compared the ligandability of BSA:NCHCHF with the interaction sites in the Human Islet Amyloid Polypeptide (hIAPP:NCHCHF, and in the amyloid pharmacophore fragments (Aβ17-42 and Aβ16-21:NCHCHF. We posit that the merging of this interaction sites is a meta-structure of pharmacophore which allows the development of chaperones that can prevent protein aggregation at various states from: stabilizing the native state to destabilizing oligomeric state and protofilament. Furthermore to stabilize fibrillar structures, thus decreasing the amount of toxic oligomers in solution, as is the case with the NCHCHF. The paper demonstrates how a set of NCHCHF can be used for studying and potentially treating the various physiopathological stages of a conformational disease. For instance, when dealing with an acute phase of cytotoxicity, what is needed is the recruitment of cytotoxic oligomers, thus chaperone F, which accelerates fiber formation, would be very useful; whereas in a chronic stage it is better to have chaperones A, B, C, and D, which stabilize the native and fibril structures halting self-catalysis and the creation of cytotoxic oligomers as a consequence of fiber formation. Furthermore, all the

  5. Electroweak vacuum stability in classically conformal B - L extension of the standard model

    Energy Technology Data Exchange (ETDEWEB)

    Das, Arindam; Okada, Nobuchika; Papapietro, Nathan [University of Alabama, Department of Physics and Astronomy, Alabama (United States)

    2017-02-15

    We consider the minimal U(1){sub B-L} extension of the standard model (SM) with the classically conformal invariance, where an anomaly-free U(1){sub B-L} gauge symmetry is introduced along with three generations of right-handed neutrinos and a U(1){sub B-L} Higgs field. Because of the classically conformal symmetry, all dimensional parameters are forbidden. The B - L gauge symmetry is radiatively broken through the Coleman-Weinberg mechanism, generating the mass for the U(1){sub B-L} gauge boson (Z{sup '} boson) and the right-handed neutrinos. Through a small negative coupling between the SM Higgs doublet and the B - L Higgs field, the negative mass term for the SM Higgs doublet is generated and the electroweak symmetry is broken. In this model context, we investigate the electroweak vacuum instability problem in the SM. It is well known that in the classically conformal U(1){sub B-L} extension of the SM, the electroweak vacuum remains unstable in the renormalization group analysis at the one-loop level. In this paper, we extend the analysis to the two-loop level, and perform parameter scans. We identify a parameter region which not only solve the vacuum instability problem, but also satisfy the recent ATLAS and CMS bounds from search for Z{sup '} boson resonance at the LHC Run-2. Considering self-energy corrections to the SM Higgs doublet through the right-handed neutrinos and the Z{sup '} boson, we derive the naturalness bound on the model parameters to realize the electroweak scale without fine-tunings. (orig.)

  6. Intramolecular BSSE and dispersion affect the structure of a dipeptide conformer

    Science.gov (United States)

    Hameed, Rabia; Khan, Afsar; van Mourik, Tanja

    2018-05-01

    B3LYP and MP2 calculations with the commonly-used 6-31+G(d) basis set predict qualitatively different structures for the Tyr-Gly conformer book1, which is the most stable conformer identified in a previous study. The structures differ mainly in the ψtyr Ramachandran angle (138° in the B3LYP structure and 120° in the MP2 structure). The causes for the discrepant structures are attributed to missing dispersion in the B3LYP calculations and large intramolecular BSSE in the MP2 calculations. The correct ψtyr value is estimated to be 130°. The MP2/6-31+G(d) profile identified an additional conformer, not present on the B3LYP surface, with a ψtyr value of 96° and a more folded structure. This minimum is, however, likely an artefact of large intramolecular BSSE values. We recommend the use of basis sets of at least quadruple-zeta quality in density functional theory (DFT), DFTaugmented with an empirical dispersion term (DFT-D) and second-order Møller-Plesset perturbation theory (MP2 ) calculations in cases where intramolecular BSSE is expected to be large.

  7. Microflora and structural stability of soils

    International Nuclear Information System (INIS)

    Guckert, A.; Chone, Therese; Jacquin, F.; Institut National Polytechnique, 54 - Nancy; Centre National de la Recherche Scientifique, 54 - Vandoeuvre-les-Nancy

    1975-01-01

    Water stable aggregates produced during the incubation of a loamy soil amended with glucose 14 C show a quite differing evolution of their physical properties and their organic matter according to the time of incubation after which they have been isolated from the soil by water sieving. The aggregates, built up during the first week of incubation, therefore during the maximal activity stage of the microflora of the soil, present the highest stability against biodegradation induced by a second incubation process, even if this one has reached six weeks. This evolution of the physical properties of the aggregates, is essentially in relationship with the microbially synthetized organic matter and especially the polysaccharides preferentially incorporated into the humine fraction. This relatively labile microbial humine has a high aggregating effect, the polysaccharide chains forming several bonds between the neighbouring clay surfaces and building up stable structural units. The mechanical strength of these aggregates is related to the stabilization of the humine produced previously and whose evolution towards a relatively stable form seems to be the result of two mechanisms: a secundary biodegradation parallel to a higher humification process of the organic matter and a increase of the bonds between polysaccharides and clay surfaces favoured by the alternation of wetting and drying [fr

  8. Central ions and lateral asparagine/glutamine zippers stabilize the post-fusion hairpin conformation of the SARS coronavirus spike glycoprotein

    International Nuclear Information System (INIS)

    Duquerroy, Stephane; Vigouroux, Armelle; Rottier, Peter J.M.; Rey, Felix A.; Jan Bosch, Berend

    2005-01-01

    The coronavirus spike glycoprotein is a class I membrane fusion protein with two characteristic heptad repeat regions (HR1 and HR2) in its ectodomain. Here, we report the X-ray structure of a previously characterized HR1/HR2 complex of the severe acute respiratory syndrome coronavirus spike protein. As expected, the HR1 and HR2 segments are organized in antiparallel orientations within a rod-like molecule. The HR1 helices form an exceptionally long (120 A) internal coiled coil stabilized by hydrophobic and polar interactions. A striking arrangement of conserved asparagine and glutamine residues of HR1 propagates from two central chloride ions, providing hydrogen-bonding 'zippers' that strongly constrain the path of the HR2 main chain, forcing it to adopt an extended conformation at either end of a short HR2 α-helix

  9. Crystal Nucleation of Tolbutamide in Solution: Relationship to Solvent, Solute Conformation, and Solution Structure.

    Science.gov (United States)

    Zeglinski, Jacek; Kuhs, Manuel; Khamar, Dikshitkumar; Hegarty, Avril C; Devi, Renuka K; Rasmuson, Åke C

    2018-04-03

    The influence of the solvent in nucleation of tolbutamide, a medium-sized, flexible and polymorphic organic molecule, has been explored by measuring nucleation induction times, estimating solvent-solute interaction enthalpies using molecular modelling and calorimetric data, probing interactions and clustering with spectroscopy, and modelling solvent-dependence of molecular conformation in solution. The nucleation driving force required to reach the same induction time is strongly solvent-dependent, increasing in the order: acetonitrilenucleation difficulty is a function of the strength of solvent-solute interaction, with emphasis on the interaction with specific H-bonding polar sites of importance in the crystal structure. A clear exception from this rule is the most difficult nucleation in toluene despite the weakest solvent-solute interactions. However molecular dynamics modelling predicts that tolbutamide assumes an intramolecularly H-bonded conformation in toluene, substantially different from and more stable than the conformation in the crystal structure, and thus presenting an additional barrier to nucleation. This explains why nucleation in toluene is the most difficult and why the relatively higher propensity for aggregation of tolbutamide molecules in toluene solution, as observed with FTIR spectroscopy, does not translate into easier nucleation. Thus, our combined experimental and molecular modelling study suggests that the solvent can influence on the nucleation not only via differences in the desolvation but also through the influence on molecular conformation. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Engineering polyelectrolyte multilayer structure at the nanometer length scale by tuning polymer solution conformation.

    Science.gov (United States)

    Boddohi, Soheil; Killingsworth, Christopher; Kipper, Matt

    2008-03-01

    Chitosan (a weak polycation) and heparin (a strong polyanion) are used to make polyelectrolyte multilayers (PEM). PEM thickness and composition are determined as a function of solution pH (4.6 to 5.8) and ionic strength (0.1 to 0.5 M). Over this range, increasing pH increases the PEM thickness; however, the sensitivity to changes in pH is a strong function of ionic strength. The PEM thickness data are correlated to the polymer conformation in solution. Polyelectrolyte conformation in solution is characterized by gel permeation chromatography (GPC). The highest sensitivity of PEM structure to pH is obtained at intermediate ionic strength. Different interactions govern the conformation and adsorption phenomena at low and high ionic strength, leading to reduced sensitivity to solution pH at extreme ionic strengths. The correspondence between PEM thickness and polymer solution conformation offers opportunities to tune polymer thin film structure at the nanometer length scale by controlling simple, reproducible processing conditions.

  11. A study of the conformation and stability of nitroxide free radicals

    International Nuclear Information System (INIS)

    Briere, R.

    1969-03-01

    The first part of this study is an application of nuclear magnetic resonance to the determination of the sign and magnitude of the long range nuclear-electron spin-spin couplings in the free radical nitroxide derived from piperidine. It has been shown that the coupling constants of the protons γ to the nitrogen atom have a pronounced spatial dependence as do the protons in the β position, a point which has not been brought out by previous investigations. Conformational analysis of these compounds has been carried out by measurement of the effect of temperature on the NMR spectra at 310 MHz. The synthesis of di-t-Bu nitroxide labelled with C 13 in the α-position made possible the unambiguous determination of the corresponding 13 C nuclear-electron spin-spin coupling constant, a parameter which had not previously been measured. The coupling constants measured in the 2,2,6,6-tetramethyl piperidine series could then be attributed to the 13 C atoms in the β-position and their variation related to the conformations of the heterocycles. This constitutes the second part of the work reported here. The final section is devoted to a study of the decomposition of an unstable nitroxide having a hydrogen atom in the p-position. This decomposition is bimolecular and the primary isotope effect shows that the rupture. of the C-H bond is involved. From this one can conclude that a nitroxide is stable when the different groups attached to the nitrogen atom cannot give rise to a decomposition either intra molecularly, if the molecular geometry is suitable, or inter molecularly by dimerisation through attack on a different center of a neighbouring molecule thus leading to a fragmentation or a disproportionation. (author) [fr

  12. Early structure of LPG partially premixed conically stabilized flames

    KAUST Repository

    Elbaz, Ayman M.

    2013-01-01

    This paper presents experimental investigation of LPG partially premixed turbulent flames stabilized within a conical nozzle burner under constant degree of partial premixing. The stability limits and mean flame structure are presented based

  13. Computational design and biophysical characterization of aggregation-resistant point mutations for γD crystallin illustrate a balance of conformational stability and intrinsic aggregation propensity.

    Science.gov (United States)

    Sahin, Erinc; Jordan, Jacob L; Spatara, Michelle L; Naranjo, Andrea; Costanzo, Joseph A; Weiss, William F; Robinson, Anne Skaja; Fernandez, Erik J; Roberts, Christopher J

    2011-02-08

    γD crystallin is a natively monomeric eye-lens protein that is associated with hereditary juvenile cataract formation. It is an attractive model system as a multidomain Greek-key protein that aggregates through partially folded intermediates. Point mutations M69Q and S130P were used to test (1) whether the protein-design algorithm RosettaDesign would successfully predict mutants that are resistant to aggregation when combined with informatic sequence-based predictors of peptide aggregation propensity and (2) how the mutations affected relative unfolding free energies (ΔΔG(un)) and intrinsic aggregation propensity (IAP). M69Q was predicted to have ΔΔG(un) ≫ 0, without significantly affecting IAP. S130P was predicted to have ΔΔG(un) ∼ 0 but with reduced IAP. The stability, conformation, and aggregation kinetics in acidic solution were experimentally characterized and compared for the variants and wild-type (WT) protein using circular dichroism and intrinsic fluorescence spectroscopy, calorimetric and chemical unfolding, thioflavin-T binding, chromatography, static laser light scattering, and kinetic modeling. Monomer secondary and tertiary structures of both variants were indistinguishable from WT, while ΔΔG(un) > 0 for M69Q and ΔΔG(un) < 0 for S130P. Surprisingly, despite being the least conformationally stable, S130P was the most resistant to aggregation, indicating a significant decrease of its IAP compared to WT and M69Q.

  14. 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.

  15. Conformational Stability of the NH2-Terminal Propeptide of the Precursor of Pulmonary Surfactant Protein SP-B.

    Directory of Open Access Journals (Sweden)

    Ángeles Bañares-Hidalgo

    Full Text Available Assembly of pulmonary surfactant lipid-protein complexes depends on conformational changes coupled with proteolytic maturation of proSP-B, the precursor of pulmonary surfactant protein B (SP-B, along the surfactant biogenesis pathway in pneumocytes. Conformational destabilization of the N-terminal propeptide of proSP-B (SP-BN triggers exposure of the mature SP-B domain for insertion into surfactant lipids. We have studied the conformational stability during GdmCl- or urea-promoted unfolding of SP-BN with trp fluorescence and circular dichroism spectroscopies. Binding of the intermediate states to bis-ANS suggests their molten globule-like character. ΔG0H2O was ~ 12.7 kJ·mol-1 either with urea or GdmCl. None of the thermal transitions of SP-BN detected by CD correspond to protein unfolding. Differential scanning calorimetry of SP-BN evidenced two endothermic peaks involved in oligomer dissociation as confirmed with 2 M urea. Ionic strength was relevant since at 150 mM NaCl, the process originating the endotherm at the highest temperature was irreversible (Tm2 = 108.5°C with an activation energy of 703.8 kJ·mol-1. At 500 mM NaCl the process became reversible (Tm2 = 114.4°C and data were fitted to the Non-two States model with two subpeaks. No free thiols in the propeptide could be titrated by DTNB with or without 5.7 M GdmCl, indicating disulfide bonds establishment.

  16. Impact of graphene-based nanomaterials (GBNMs) on the structural and functional conformations of hepcidin peptide

    Science.gov (United States)

    Singh, Krishna P.; Baweja, Lokesh; Wolkenhauer, Olaf; Rahman, Qamar; Gupta, Shailendra K.

    2018-03-01

    Graphene-based nanomaterials (GBNMs) are widely used in various industrial and biomedical applications. GBNMs of different compositions, size and shapes are being introduced without thorough toxicity evaluation due to the unavailability of regulatory guidelines. Computational toxicity prediction methods are used by regulatory bodies to quickly assess health hazards caused by newer materials. Due to increasing demand of GBNMs in various size and functional groups in industrial and consumer based applications, rapid and reliable computational toxicity assessment methods are urgently needed. In the present work, we investigate the impact of graphene and graphene oxide nanomaterials on the structural conformations of small hepcidin peptide and compare the materials for their structural and conformational changes. Our molecular dynamics simulation studies revealed conformational changes in hepcidin due to its interaction with GBMNs, which results in a loss of its functional properties. Our results indicate that hepcidin peptide undergo severe structural deformations when superimposed on the graphene sheet in comparison to graphene oxide sheet. These observations suggest that graphene is more toxic than a graphene oxide nanosheet of similar area. Overall, this study indicates that computational methods based on structural deformation, using molecular dynamics (MD) simulations, can be used for the early evaluation of toxicity potential of novel nanomaterials.

  17. Replacement of Ser108 in Plasmodium falciparum enolase results in weak Mg(II) binding: role of a parasite-specific pentapeptide insert in stabilizing the active conformation of the enzyme.

    Science.gov (United States)

    Dutta, Sneha; Mukherjee, Debanjan; Jarori, Gotam K

    2015-06-01

    A distinct structural feature of Plasmodium falciparum enolase (Pfeno) is the presence of a five amino acid insert -104EWGWS108- that is not found in host enolases. Its conservation among apicomplexan enolases has raised the possibility of its involvement in some important physiological function(s). Deletion of this sequence is known to lower k(cat)/K(m), increase K(a) for Mg(II) and convert dimer into monomers (Vora HK, Shaik FR, Pal-Bhowmick I, Mout R & Jarori GK (2009) Arch Biochem Biophys 485, 128-138). These authors also raised the possibility of the formation of an H-bond between Ser108 and Leu49 that could stabilize the apo-Pfeno in an active closed conformation that has high affinity for Mg(II). Here, we examined the effect of replacement of Ser108 with Gly/Ala/Thr on enzyme activity, Mg(II) binding affinity, conformational states and oligomeric structure and compared it with native recombinant Pfeno. The results obtained support the view that Ser108 is likely to be involved in the formation of certain crucial H-bonds with Leu49. The presence of these interactions can stabilize apo-Pfeno in an active closed conformation similar to that of Mg(II) bound yeast enolase. As predicted, S108G/A-Pfeno variants (where Ser108-Leu49 H-bonds are likely to be disrupted) were found to exist in an open conformation and had low affinity for Mg(II). They also required Mg(II) induced conformational changes to acquire the active closed conformational state essential for catalysis. The possible physiological relevance of apo-Pfeno being in such an active state is discussed. © 2015 FEBS.

  18. Characteristic conformation of Mosher's amide elucidated using the cambridge structural database.

    Science.gov (United States)

    Ichikawa, Akio; Ono, Hiroshi; Mikata, Yuji

    2015-07-16

    Conformations of the crystalline 3,3,3-trifluoro-2-methoxy-2-phenylpropanamide derivatives (MTPA amides) deposited in the Cambridge Structural Database (CSD) were examined statistically as Racid-enantiomers. The majority of dihedral angles (48/58, ca. 83%) of the amide carbonyl groups and the trifluoromethyl groups ranged from -30° to 0° with an average angle θ1 of -13°. The other conformational properties were also clarified: (1) one of the fluorine atoms was antiperiplanar (ap) to the amide carbonyl group, forming a staggered conformation; (2) the MTPA amides prepared from primary amines showed a Z form in amide moieties; (3) in the case of the MTPA amide prepared from a primary amine possessing secondary alkyl groups (i.e., Mosher-type MTPA amide), the dihedral angles between the methine groups and the carbonyl groups were syn and indicative of a moderate conformational flexibility; (4) the phenyl plane was inclined from the O-Cchiral bond of the methoxy moiety with an average dihedral angle θ2 of +21°; (5) the methyl group of the methoxy moiety was ap to the ipso-carbon atom of the phenyl group.

  19. Conformational transition paths harbor structures useful for aiding drug discovery and understanding enzymatic mechanisms in protein kinases.

    Science.gov (United States)

    Wong, Chung F

    2016-01-01

    This short article examines the usefulness of fast simulations of conformational transition paths in elucidating enzymatic mechanisms and guiding drug discovery for protein kinases. It applies the transition path method in the MOIL software package to simulate the paths of conformational transitions between six pairs of structures from the Protein Data Bank. The structures along the transition paths were found to resemble experimental structures that mimic transient structures believed to form during enzymatic catalysis or conformational transitions, or structures that have drug candidates bound. These findings suggest that such simulations could provide quick initial insights into the enzymatic mechanisms or pathways of conformational transitions of proteins kinases, or could provide structures useful for aiding structure-based drug design. © 2015 The Protein Society.

  20. Crystalline structure of the marketed form of Rifampicin: a case of conformational and charge transfer polymorphism

    Science.gov (United States)

    de Pinho Pessoa Nogueira, Luciana; de Oliveira, Yara S.; de C. Fonseca, Jéssica; Costa, Wendell S.; Raffin, Fernanda N.; Ellena, Javier; Ayala, Alejandro Pedro

    2018-03-01

    Rifampicin is a semi-synthetic drug derived from rifamycin B, and currently integrates the fixed dose combination tablet formulations used in the treatment of tuberculosis. It is also used in the leprosy polychemotherapy and prophylaxis, which are diseases classified as neglected according to the World Health Organization. Rifampicin is a polymorphic drug and its desirable polymorphic form is labeled as II, being the main goal of this study the elucidation of its crystalline structure. Polymorph II is characterized by two molecules with different conformations in the asymmetric unit and the following lattice parameters: a = 14.0760 (10) Å, b = 17.5450 (10) Å, c = 17.5270 (10) Å, β = 92.15°. Differently to the previously reported structures, a charge transference from the hydroxyl group of the naphthoquinone of one conformer to the nitrogen of the piperazine group of the second conformer was observed. The relevance of the knowledge of this crystalline structure, which is the preferred polymorph for pharmaceutical formulations, was evidenced by analyzing raw materials with polymorphic mixtures. Thus, the results presented in this contribution close an old information gap allowing the complete solid-state characterization of rifampicin.

  1. Structural investigation of ribonuclease A conformational preferences using high pressure protein crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Kurpiewska, Katarzyna, E-mail: kurpiews@chemia.uj.edu.pl [Jagiellonian University, Faculty of Chemistry, Department of Crystal Chemistry and Crystal Physics, Protein Crystallography Group, Ingardena 3, 30-060 Kraków (Poland); Dziubek, Kamil; Katrusiak, Andrzej [Adam Mickiewicz University, Faculty of Chemistry, Department of Materials Chemistry, Umultowska 89b, 61-61 Poznań (Poland); Font, Josep [School of Medical Science, University of Sydney, NSW 2006 (Australia); Ribò, Marc; Vilanova, Maria [Universitat de Girona, Laboratorid’Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Campus de Montilivi, 17071 Girona (Spain); Lewiński, Krzysztof [Jagiellonian University, Faculty of Chemistry, Department of Crystal Chemistry and Crystal Physics, Protein Crystallography Group, Ingardena 3, 30-060 Kraków (Poland)

    2016-04-01

    Highlights: • A unique crystallographic studies of wild-type and mutated form of the same protein under high pressure. • Compressibility of RNase A molecule is significantly affected by a single amino acid substitution. • High pressure protein crystallography helps understanding protein flexibility and identify conformational substrates. - Abstract: Hydrostatic pressure in range 0.1–1.5 GPa is used to modify biological system behaviour mostly in biophysical studies of proteins in solution. Due to specific influence on the system equilibrium high pressure can act as a filter that enables to identify and investigate higher energy protein conformers. The idea of the presented experiments is to examine the behaviour of RNase A molecule under high pressure before and after introduction of destabilizing mutation. For the first time crystal structures of wild-type bovine pancreatic ribonuclease A and its markedly less stable variant modified at position Ile106 were determined at different pressures. X-ray diffraction experiments at high pressure showed that the secondary structure of RNase A is well preserved even beyond 0.67 GPa at room temperature. Detailed structural analysis of ribonuclease A conformation observed under high pressure revealed that pressure influences hydrogen bonds pattern, cavity size and packing of molecule.

  2. Structural investigation of ribonuclease A conformational preferences using high pressure protein crystallography

    International Nuclear Information System (INIS)

    Kurpiewska, Katarzyna; Dziubek, Kamil; Katrusiak, Andrzej; Font, Josep; Ribò, Marc; Vilanova, Maria; Lewiński, Krzysztof

    2016-01-01

    Highlights: • A unique crystallographic studies of wild-type and mutated form of the same protein under high pressure. • Compressibility of RNase A molecule is significantly affected by a single amino acid substitution. • High pressure protein crystallography helps understanding protein flexibility and identify conformational substrates. - Abstract: Hydrostatic pressure in range 0.1–1.5 GPa is used to modify biological system behaviour mostly in biophysical studies of proteins in solution. Due to specific influence on the system equilibrium high pressure can act as a filter that enables to identify and investigate higher energy protein conformers. The idea of the presented experiments is to examine the behaviour of RNase A molecule under high pressure before and after introduction of destabilizing mutation. For the first time crystal structures of wild-type bovine pancreatic ribonuclease A and its markedly less stable variant modified at position Ile106 were determined at different pressures. X-ray diffraction experiments at high pressure showed that the secondary structure of RNase A is well preserved even beyond 0.67 GPa at room temperature. Detailed structural analysis of ribonuclease A conformation observed under high pressure revealed that pressure influences hydrogen bonds pattern, cavity size and packing of molecule.

  3. New insights into structural determinants of prion protein folding and stability.

    Science.gov (United States)

    Benetti, Federico; Legname, Giuseppe

    2015-01-01

    Prions are the etiological agent of fatal neurodegenerative diseases called prion diseases or transmissible spongiform encephalopathies. These maladies can be sporadic, genetic or infectious disorders. Prions are due to post-translational modifications of the cellular prion protein leading to the formation of a β-sheet enriched conformer with altered biochemical properties. The molecular events causing prion formation in sporadic prion diseases are still elusive. Recently, we published a research elucidating the contribution of major structural determinants and environmental factors in prion protein folding and stability. Our study highlighted the crucial role of octarepeats in stabilizing prion protein; the presence of a highly enthalpically stable intermediate state in prion-susceptible species; and the role of disulfide bridge in preserving native fold thus avoiding the misfolding to a β-sheet enriched isoform. Taking advantage from these findings, in this work we present new insights into structural determinants of prion protein folding and stability.

  4. Cryo-electron Microscopy Structures of Expanded Poliovirus with VHHs Sample the Conformational Repertoire of the Expanded State.

    Science.gov (United States)

    Strauss, Mike; Schotte, Lise; Karunatilaka, Krishanthi S; Filman, David J; Hogle, James M

    2017-02-01

    By using cryo-electron microscopy, expanded 80S-like poliovirus virions (poliovirions) were visualized in complexes with four 80S-specific camelid VHHs (Nanobodies). In all four complexes, the VHHs bind to a site on the top surface of the capsid protein VP3, which is hidden in the native virus. Interestingly, although the four VHHs bind to the same site, the structures of the expanded virus differ in detail in each complex, suggesting that each of the Nanobodies has sampled a range of low-energy structures available to the expanded virion. By stabilizing unique structures of expanded virions, VHH binding permitted a more detailed view of the virus structure than was previously possible, leading to a better understanding of the expansion process that is a critical step in infection. It is now clear which polypeptide chains become disordered and which become rearranged. The higher resolution of these structures also revealed well-ordered conformations for the EF loop of VP2, the GH loop of VP3, and the N-terminal extensions of VP1 and VP2, which, in retrospect, were present in lower-resolution structures but not recognized. These structural observations help to explain preexisting mutational data and provide insights into several other stages of the poliovirus life cycle, including the mechanism of receptor-triggered virus expansion. When poliovirus infects a cell, it undergoes a change in its structure in order to pass RNA through its protein coat, but this altered state is short-lived and thus poorly understood. The structures of poliovirus bound to single-domain antibodies presented here capture the altered virus in what appear to be intermediate states. A careful analysis of these structures lets us better understand the molecular mechanism of infection and how these changes in the virus lead to productive-infection events. Copyright © 2017 American Society for Microbiology.

  5. Neutron Star Structure in the Presence of Conformally Coupled Scalar Fields

    Science.gov (United States)

    Sultana, Joseph; Bose, Benjamin; Kazanas, Demosthenes

    2014-01-01

    Neutron star models are studied in the context of scalar-tensor theories of gravity in the presence of a conformally coupled scalar field, using two different numerical equations of state (EoS) representing different degrees of stiffness. In both cases we obtain a complete solution by matching the interior numerical solution of the coupled Einstein-scalar field hydrostatic equations, with an exact metric on the surface of the star. These are then used to find the effect of the scalar field and its coupling to geometry, on the neutron star structure, particularly the maximum neutron star mass and radius. We show that in the presence of a conformally coupled scalar field, neutron stars are less dense and have smaller masses and radii than their counterparts in the minimally coupled case, and the effect increases with the magnitude of the scalar field at the center of the star.

  6. Optical spectroscopic methods for probing the conformational stability of immobilised enzymes.

    Science.gov (United States)

    Ganesan, Ashok; Moore, Barry D; Kelly, Sharon M; Price, Nicholas C; Rolinski, Olaf J; Birch, David J S; Dunkin, Ian R; Halling, Peter J

    2009-07-13

    We report the development of biophysical techniques based on circular dichroism (CD), diffuse reflectance infrared Fourier transform (DRIFT) and tryptophan (Trp) fluorescence to investigate in situ the structure of enzymes immobilised on solid particles. Their applicability is demonstrated using subtilisin Carlsberg (SC) immobilised on silica gel and Candida antartica lipase B immobilised on Lewatit VP.OC 1600 (Novozyme 435). SC shows nearly identical secondary structure in solution and in the immobilised state as evident from far UV CD spectra and amide I vibration bands. Increased near UV CD intensity and reduced Trp fluorescence suggest a more rigid tertiary structure on the silica surface. After immobilised SC is inactivated, these techniques reveal: a) almost complete loss of near UV CD signal, suggesting loss of tertiary structure; b) a shift in the amide I vibrational band from 1658 cm(-1) to 1632 cm(-1), indicating a shift from alpha-helical structure to beta-sheet; c) a substantial blue shift and reduced dichroism in the far UV CD, supporting a shift to beta-sheet structure; d) strong increase in Trp fluorescence intensity, which reflects reduced intramolecular quenching with loss of tertiary structure; and e) major change in fluorescence lifetime distribution, confirming a substantial change in Trp environment. DRIFT measurements suggest that pressing KBr discs may perturb protein structure. With the enzyme on organic polymer it was possible to obtain near UV CD spectra free of interference by the carrier material. However, far UV CD, DRIFT and fluorescence measurements showed strong signals from the organic support. In conclusion, the spectroscopic methods described here provide structural information hitherto inaccessible, with their applicability limited by interference from, rather than the particulate nature of, the support material.

  7. Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor.

    Science.gov (United States)

    Che, Tao; Majumdar, Susruta; Zaidi, Saheem A; Ondachi, Pauline; McCorvy, John D; Wang, Sheng; Mosier, Philip D; Uprety, Rajendra; Vardy, Eyal; Krumm, Brian E; Han, Gye Won; Lee, Ming-Yue; Pardon, Els; Steyaert, Jan; Huang, Xi-Ping; Strachan, Ryan T; Tribo, Alexandra R; Pasternak, Gavril W; Carroll, F Ivy; Stevens, Raymond C; Cherezov, Vadim; Katritch, Vsevolod; Wacker, Daniel; Roth, Bryan L

    2018-01-11

    The κ-opioid receptor (KOP) mediates the actions of opioids with hallucinogenic, dysphoric, and analgesic activities. The design of KOP analgesics devoid of hallucinatory and dysphoric effects has been hindered by an incomplete structural and mechanistic understanding of KOP agonist actions. Here, we provide a crystal structure of human KOP in complex with the potent epoxymorphinan opioid agonist MP1104 and an active-state-stabilizing nanobody. Comparisons between inactive- and active-state opioid receptor structures reveal substantial conformational changes in the binding pocket and intracellular and extracellular regions. Extensive structural analysis and experimental validation illuminate key residues that propagate larger-scale structural rearrangements and transducer binding that, collectively, elucidate the structural determinants of KOP pharmacology, function, and biased signaling. These molecular insights promise to accelerate the structure-guided design of safer and more effective κ-opioid receptor therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Restricted N-glycan conformational space in the PDB and its implication in glycan structure modeling.

    Science.gov (United States)

    Jo, Sunhwan; Lee, Hui Sun; Skolnick, Jeffrey; Im, Wonpil

    2013-01-01

    Understanding glycan structure and dynamics is central to understanding protein-carbohydrate recognition and its role in protein-protein interactions. Given the difficulties in obtaining the glycan's crystal structure in glycoconjugates due to its flexibility and heterogeneity, computational modeling could play an important role in providing glycosylated protein structure models. To address if glycan structures available in the PDB can be used as templates or fragments for glycan modeling, we present a survey of the N-glycan structures of 35 different sequences in the PDB. Our statistical analysis shows that the N-glycan structures found on homologous glycoproteins are significantly conserved compared to the random background, suggesting that N-glycan chains can be confidently modeled with template glycan structures whose parent glycoproteins share sequence similarity. On the other hand, N-glycan structures found on non-homologous glycoproteins do not show significant global structural similarity. Nonetheless, the internal substructures of these N-glycans, particularly, the substructures that are closer to the protein, show significantly similar structures, suggesting that such substructures can be used as fragments in glycan modeling. Increased interactions with protein might be responsible for the restricted conformational space of N-glycan chains. Our results suggest that structure prediction/modeling of N-glycans of glycoconjugates using structure database could be effective and different modeling approaches would be needed depending on the availability of template structures.

  9. Restricted N-glycan conformational space in the PDB and its implication in glycan structure modeling.

    Directory of Open Access Journals (Sweden)

    Sunhwan Jo

    Full Text Available Understanding glycan structure and dynamics is central to understanding protein-carbohydrate recognition and its role in protein-protein interactions. Given the difficulties in obtaining the glycan's crystal structure in glycoconjugates due to its flexibility and heterogeneity, computational modeling could play an important role in providing glycosylated protein structure models. To address if glycan structures available in the PDB can be used as templates or fragments for glycan modeling, we present a survey of the N-glycan structures of 35 different sequences in the PDB. Our statistical analysis shows that the N-glycan structures found on homologous glycoproteins are significantly conserved compared to the random background, suggesting that N-glycan chains can be confidently modeled with template glycan structures whose parent glycoproteins share sequence similarity. On the other hand, N-glycan structures found on non-homologous glycoproteins do not show significant global structural similarity. Nonetheless, the internal substructures of these N-glycans, particularly, the substructures that are closer to the protein, show significantly similar structures, suggesting that such substructures can be used as fragments in glycan modeling. Increased interactions with protein might be responsible for the restricted conformational space of N-glycan chains. Our results suggest that structure prediction/modeling of N-glycans of glycoconjugates using structure database could be effective and different modeling approaches would be needed depending on the availability of template structures.

  10. Unravelling the Conformational Landscape of Nicotinoids: the Structure of Cotinine by Broadband Rotational Spectroscopy

    Science.gov (United States)

    Uriarte, Iciar; Ecija, Patricia; Cocinero, Emilio J.; Perez, Cristobal; Caballero-Mancebo, Elena; Lesarri, Alberto

    2015-06-01

    Alkaloids such as nicotine, cotinine or anabasine share a common floppy structural motif consisting of a two-ring assembly with a 3-pyridil methylamine skeleton. In order to investigate the structure-activity relationship of these biomolecules, structural studies with rotational resolution have been carried out for nicotine and anabasine in the gas phase, where these molecules can be probed in an "interaction-free" environment (no solvent or crystal-packing interactions). We hereby present a structural investigation of cotinine in a jet expansion using the chirped-pulse Fourier-transform microwave (CP-FTMW) spectrometer recently built at the University of the Basque Country (UPV-EHU). The rotational spectrum (6-18 GHz) reveals the presence of two different conformations. The conformational preferences of cotinine originate from the internal rotation of the two ring moieties, the detected species differing in a near 180° rotation of pyridine. The final structure is modulated by steric effects. J.-U. Grabow, S. Mata, J. L. Alonso, I. Peña, S. Blanco, J. C. López, C. Cabezas, Phys. Chem. Chem. Phys. 2011, 13, 21063. A. Lesarri, E. J. Cocinero, L. Evangelisti, R. D. Suenram, W. Caminati, J.-U. Grabow, Chem. Eur. J. 2010, 16, 10214.

  11. Cationic oligopeptides with the repeating sequence L-Lysyl-L-alanyl-L-alanine: conformational and thermal stability stuydy using optical spectroscopic methods

    Czech Academy of Sciences Publication Activity Database

    Setnička, V.; Hlaváček, Jan; Urbanová, J.

    2009-01-01

    Roč. 15, č. 8 (2009), s. 533-539 ISSN 1075-2617 Institutional research plan: CEZ:AV0Z40550506 Keywords : cationic peptides * conformation * thermal stability * vibrational circular dichroism Subject RIV: CC - Organic Chemistry Impact factor: 1.807, year: 2009

  12. A study on the development of regulatory guide to stability conformation and classification criteria of low and intermediate level radioactive waste

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Geon Jae; Paek, Min Hoon; Park, Jong Gil; Han, Byeong Seop; Cheong, Jae Hak; Lee, Hae Chan; Yang, Jin Yeong; Hong, Hei Kwan; Park, Jin Baek [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1994-01-15

    The objectives of this study are to examine basic principles and terms and to suggest and recommend definite methods and criteria necessary for the classification and stability conformation of radioactive wastes. In this study, following studies were performed : investigate the domestic regulations related with the stability conformation and classification of radioactive wastes in order to keep mutual relationship and consistency between the regulations, investigate the sources, types and characteristics of domestic radioactive wastes as a basis for this study, investigate the classification criteria and methods of others countries in a general point of view and in the view point of disposal method, select the classification criteria factors for the domestic case and general case in the both general and domestic points of view, investigate the general test items for the stability conformation of radioactive waste forms and analysis on the test items and criteria of others countries for the mined cavity disposal and shallow land disposal in the view point of disposal method, experimental leaching and immersion tests for the borate and spent resin wastes as a study on the stability conformation of waste forms, selection of acceptance criteria for the both of disposal methods in the domestic and general cases.

  13. The Incorporation of Ribonucleotides Induces Structural and Conformational Changes in DNA.

    Science.gov (United States)

    Meroni, Alice; Mentegari, Elisa; Crespan, Emmanuele; Muzi-Falconi, Marco; Lazzaro, Federico; Podestà, Alessandro

    2017-10-03

    Ribonucleotide incorporation is the most common error occurring during DNA replication. Cells have hence developed mechanisms to remove ribonucleotides from the genome and restore its integrity. Indeed, the persistence of ribonucleotides into DNA leads to severe consequences, such as genome instability and replication stress. Thus, it becomes important to understand the effects of ribonucleotides incorporation, starting from their impact on DNA structure and conformation. Here we present a systematic study of the effects of ribonucleotide incorporation into DNA molecules. We have developed, to our knowledge, a new method to efficiently synthesize long DNA molecules (hundreds of basepairs) containing ribonucleotides, which is based on a modified protocol for the polymerase chain reaction. By means of atomic force microscopy, we could therefore investigate the changes, upon ribonucleotide incorporation, of the structural and conformational properties of numerous DNA populations at the single-molecule level. Specifically, we characterized the scaling of the contour length with the number of basepairs and the scaling of the end-to-end distance with the curvilinear distance, the bending angle distribution, and the persistence length. Our results revealed that ribonucleotides affect DNA structure and conformation on scales that go well beyond the typical dimension of the single ribonucleotide. In particular, the presence of ribonucleotides induces a systematic shortening of the molecules, together with a decrease of the persistence length. Such structural changes are also likely to occur in vivo, where they could directly affect the downstream DNA transactions, as well as interfere with protein binding and recognition. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. High-throughput screening to identify inhibitors which stabilize inactive kinase conformations in p38 alpha

    NARCIS (Netherlands)

    Simard, J.R.; Grutter, C.; Pawar, V.; Aust, B.; Wolf, A.; Rabiller, M.; Wulfert, S.; Robubi, A.; Kluter, S.; Ottmann, C.; Rauh, D.

    2009-01-01

    Small molecule kinase inhibitors are an attractive means to modulate kinase activities in medicinal chemistry and chemical biology research. In the physiological setting of a cell, kinase function is orchestrated by a plethora of regulatory processes involving the structural transition of kinases

  15. Oculocutaneous albinism type 1: link between mutations, tyrosinase conformational stability, and enzymatic activity.

    Science.gov (United States)

    Dolinska, Monika B; Kus, Nicole J; Farney, S Katie; Wingfield, Paul T; Brooks, Brian P; Sergeev, Yuri V

    2017-01-01

    Oculocutaneous albinism type 1 (OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene. Two subtypes of OCA1 have been described: severe OCA1A with complete absence of tyrosinase activity and less severe OCA1B with residual tyrosinase activity. Here, we characterize the recombinant human tyrosinase intramelanosomal domain and mutant variants, which mimic genetic changes in both subtypes of OCA1 patients. Proteins were prepared using site-directed mutagenesis, expressed in insect larvae, purified by chromatography, and characterized by enzymatic activities, tryptophan fluorescence, and Gibbs free energy changes. The OCA1A mutants showed very low protein expression and protein yield and are enzymatically inactive. Mutants mimicking OCA1B were biochemically similar to the wild type, but exhibited lower specific activities and protein stabilities. The results are consistent with clinical data, which indicates that OCA1A mutations inactivate tyrosinase and result in severe phenotype, while OCA1B mutations partially inactivate tyrosinase and result in OCA1B albinism. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  16. The analytic structure of conformal blocks and the generalized Wilson-Fisher fixed points

    Energy Technology Data Exchange (ETDEWEB)

    Gliozzi, Ferdinando [Dipartimento di Fisica, Università di Torino andIstituto Nazionale di Fisica Nucleare - sezione di Torino,Via P. Giuria 1, I-10125 Torino (Italy); Guerrieri, Andrea L. [Department of Physics, Faculty of Science, Chulalongkorn University,Thanon Phayathai, Pathumwan, Bangkok 10330 (Thailand); I.N.F.N. Sezione di Roma Tor Vergata,Via della Ricerca Scientifica, I-00133 Roma (Italy); Petkou, Anastasios C. [Institute of Theoretical Physics, Aristotle University of Thessaloniki,54124 Thessaloniki (Greece); Wen, Congkao [Walter Burke Institute for Theoretical Physics, California Institute of Technology,Pasadena, CA 91125 (United States); Mani L. Bhaumik Institute for Theoretical Physics,Department of Physics and Astronomy, UCLA,Los Angeles, CA 90095 (United States)

    2017-04-11

    We describe in detail the method used in our previous work https://arxiv.org/abs/1611.10344 to study the Wilson-Fisher critical points nearby generalized free CFTs, exploiting the analytic structure of conformal blocks as functions of the conformal dimension of the exchanged operator. Our method is equivalent to the mechanism of conformal multiplet recombination set up by null states. We compute, to the first non-trivial order in the ϵ-expansion, the anomalous dimensions and the OPE coefficients of infinite classes of scalar local operators using just CFT data. We study single-scalar and O(N)-invariant theories, as well as theories with multiple deformations. When available we agree with older results, but we also produce a wealth of new ones. Unitarity and crossing symmetry are not used in our approach and we are able to apply our method to non-unitary theories as well. Some implications of our results for the study of the non-unitary theories containing partially conserved higher-spin currents are briefly mentioned.

  17. Conformity and structure of titanium oxide films grown by atomic layer deposition on silicon substrates

    Energy Technology Data Exchange (ETDEWEB)

    Jogi, Indrek [University of Tartu, Institute of Experimental Physics and Technology, Taehe 4, 51010, Tartu (Estonia)], E-mail: indrek.jogi@ut.ee; Paers, Martti; Aarik, Jaan; Aidla, Aleks [University of Tartu, Institute of Physics, Riia 142, 51014, Tartu (Estonia); Laan, Matti [University of Tartu, Institute of Experimental Physics and Technology, Taehe 4, 51010, Tartu (Estonia); Sundqvist, Jonas; Oberbeck, Lars; Heitmann, Johannes [Qimonda Dresden GmbH and Co. OHG, Koenigsbruecker Strasse 180, 01099, Dresden (Germany); Kukli, Kaupo [University of Tartu, Institute of Experimental Physics and Technology, Taehe 4, 51010, Tartu (Estonia)

    2008-06-02

    Conformity and phase structure of atomic layer deposited TiO{sub 2} thin films grown on silicon substrates were studied. The films were grown using TiCl{sub 4} and Ti(OC{sub 2}H{sub 5}){sub 4} as titanium precursors in the temperature range from 125 to 500 {sup o}C. In all cases perfect conformal growth was achieved on patterned substrates with elliptical holes of 7.5 {mu}m depth and aspect ratio of about 1:40. Conformal growth was achieved with process parameters similar to those optimized for the growth on planar wafers. The dominant crystalline phase in the as-grown films was anatase, with some contribution from rutile at relatively higher temperatures. Annealing in the oxygen ambient resulted in (re)crystallization whereas the effect of annealing depended markedly on the precursors used in the deposition process. Compared to films grown from TiCl{sub 4}, the films grown from Ti(OC{sub 2}H{sub 5}){sub 4} were transformed into rutile in somewhat greater extent, whereas in terms of step coverage the films grown from Ti(OC{sub 2}H{sub 5}){sub 4} remained somewhat inferior compared to the films grown from TiCl{sub 4}.

  18. Conformal covariance, modular structure, and duality for local algebras in free massless quantum field theories

    International Nuclear Information System (INIS)

    Hislop, P.D.

    1988-01-01

    The Tomita modular operators and the duality property for the local von Neumann algebras in quantum field models describing free massless particles with arbitrary helicity are studied. It is proved that the representation of the Poincare group in each model extends to a unitary representation of SU(2, 2), a covering group of the conformal group. An irreducible set of ''standard'' linear fields is shown to be covariant with respect to this representation. The von Neumann algebras associated with wedge, double-cone, and lightcone regions generated by these fields are proved to be unitarily equivalent. The modular operators for these algebras are obtained in explicit form using the conformal covariance and the results of Bisognano and Wichmann on the modular structure of the wedge algebras. The modular automorphism groups are implemented by one-parameter groups of conformal transformations. The modular conjugation operators are used to prove the duality property for the double-cone algebras and the timelike duality property for the lightcone algebras. copyright 1988 Academic Press, Inc

  19. Role of tryptophan 95 in substrate specificity and structural stability of Sulfolobus solfataricus alcohol dehydrogenase.

    Science.gov (United States)

    Pennacchio, Angela; Esposito, Luciana; Zagari, Adriana; Rossi, Mosè; Raia, Carlo A

    2009-09-01

    A mutant of the thermostable NAD(+)-dependent (S)-stereospecific alcohol dehydrogenase from Sulfolobus solfataricus (SsADH) which has a single substitution, Trp95Leu, located at the substrate binding pocket, was fully characterized to ascertain the role of Trp95 in discriminating between chiral secondary alcohols suggested by the wild-type SsADH crystallographic structure. The Trp95Leu mutant displays no apparent activity with short-chain primary and secondary alcohols and poor activity with aromatic substrates and coenzyme. Moreover, the Trp --> Leu substitution affects the structural stability of the archaeal ADH, decreasing its thermal stability without relevant changes in secondary structure. The double mutant Trp95Leu/Asn249Tyr was also purified to assist in crystallographic analysis. This mutant exhibits higher activity but decreased affinity toward aliphatic alcohols, aldehydes as well as NAD(+) and NADH compared to the wild-type enzyme. The crystal structure of the Trp95Leu/Asn249Tyr mutant apo form, determined at 2.0 A resolution, reveals a large local rearrangement of the substrate site with dramatic consequences. The Leu95 side-chain conformation points away from the catalytic metal center and the widening of the substrate site is partially counteracted by a concomitant change of Trp117 side chain conformation. Structural changes at the active site are consistent with the reduced activity on substrates and decreased coenzyme binding.

  20. Method of making large area conformable shape structures for detector/sensor applications using glass drawing technique and postprocessing

    Science.gov (United States)

    Ivanov, Ilia N [Knoxville, TN; Simpson, John T [Clinton, IN

    2012-01-24

    A method of making a large area conformable shape structure comprises drawing a plurality of tubes to form a plurality of drawn tubes, and cutting the plurality of drawn tubes into cut drawn tubes of a predetermined shape. The cut drawn tubes have a first end and a second end along the longitudinal direction of the cut drawn tubes. The method further comprises conforming the first end of the cut drawn tubes into a predetermined curve to form the large area conformable shape structure, wherein the cut drawn tubes contain a material.

  1. Stability and the structure of continuous-time economic models

    NARCIS (Netherlands)

    Nieuwenhuis, H.J.; Schoonbeek, L.

    In this paper we investigate the relationship between the stability of macroeconomic, or macroeconometric, continuous-time models and the structure of the matrices appearing in these models. In particular, we concentrate on dominant-diagonal structures. We derive general stability results for models

  2. Vanillin and isovanillin: Comparative vibrational spectroscopic studies, conformational stability and NLO properties by density functional theory calculations

    Science.gov (United States)

    Balachandran, V.; Parimala, K.

    This study is a comparative analysis of FT-IR and FT-Raman spectra of vanillin (3-methoxy-4-hydroxybenzaldehyde) and isovanillin (3-hydroxy-4-methoxybenzaldehyde). The molecular structure, vibrational wavenumbers, infrared intensities, Raman scattering activities were calculated for both molecules using the B3LYP density functional theory (DFT) with the standard 6-311++G∗∗ basis set. The computed values of frequencies are scaled using multiple scaling factors to yield good coherence with the observed values. The calculated harmonic vibrational frequencies are compared with experimental FT-IR and FT-Raman spectra. The geometrical parameters and total energies of vanillin and isovanillin were obtained for all the eight conformers (a-h) from DFT/B3LYP method with 6-311++G∗∗ basis set. The computational results identified the most stable conformer of vanillin and isovanillin as in the "a" form. Non-linear properties such as electric dipole moment (μ), polarizability (α), and hyperpolarizability (β) values of the investigated molecules have been computed using B3LYP quantum chemical calculation. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecules.

  3. Structuring detergents for extracting and stabilizing functional membrane proteins.

    Directory of Open Access Journals (Sweden)

    Rima Matar-Merheb

    Full Text Available BACKGROUND: Membrane proteins are privileged pharmaceutical targets for which the development of structure-based drug design is challenging. One underlying reason is the fact that detergents do not stabilize membrane domains as efficiently as natural lipids in membranes, often leading to a partial to complete loss of activity/stability during protein extraction and purification and preventing crystallization in an active conformation. METHODOLOGY/PRINCIPAL FINDINGS: Anionic calix[4]arene based detergents (C4Cn, n=1-12 were designed to structure the membrane domains through hydrophobic interactions and a network of salt bridges with the basic residues found at the cytosol-membrane interface of membrane proteins. These compounds behave as surfactants, forming micelles of 5-24 nm, with the critical micellar concentration (CMC being as expected sensitive to pH ranging from 0.05 to 1.5 mM. Both by 1H NMR titration and Surface Tension titration experiments, the interaction of these molecules with the basic amino acids was confirmed. They extract membrane proteins from different origins behaving as mild detergents, leading to partial extraction in some cases. They also retain protein functionality, as shown for BmrA (Bacillus multidrug resistance ATP protein, a membrane multidrug-transporting ATPase, which is particularly sensitive to detergent extraction. These new detergents allow BmrA to bind daunorubicin with a Kd of 12 µM, a value similar to that observed after purification using dodecyl maltoside (DDM. They preserve the ATPase activity of BmrA (which resets the protein to its initial state after drug efflux much more efficiently than SDS (sodium dodecyl sulphate, FC12 (Foscholine 12 or DDM. They also maintain in a functional state the C4Cn-extracted protein upon detergent exchange with FC12. Finally, they promote 3D-crystallization of the membrane protein. CONCLUSION/SIGNIFICANCE: These compounds seem promising to extract in a functional state

  4. Statistically significant dependence of the Xaa-Pro peptide bond conformation on secondary structure and amino acid sequence

    Directory of Open Access Journals (Sweden)

    Leitner Dietmar

    2005-04-01

    Full Text Available Abstract Background A reliable prediction of the Xaa-Pro peptide bond conformation would be a useful tool for many protein structure calculation methods. We have analyzed the Protein Data Bank and show that the combined use of sequential and structural information has a predictive value for the assessment of the cis versus trans peptide bond conformation of Xaa-Pro within proteins. For the analysis of the data sets different statistical methods such as the calculation of the Chou-Fasman parameters and occurrence matrices were used. Furthermore we analyzed the relationship between the relative solvent accessibility and the relative occurrence of prolines in the cis and in the trans conformation. Results One of the main results of the statistical investigations is the ranking of the secondary structure and sequence information with respect to the prediction of the Xaa-Pro peptide bond conformation. We observed a significant impact of secondary structure information on the occurrence of the Xaa-Pro peptide bond conformation, while the sequence information of amino acids neighboring proline is of little predictive value for the conformation of this bond. Conclusion In this work, we present an extensive analysis of the occurrence of the cis and trans proline conformation in proteins. Based on the data set, we derived patterns and rules for a possible prediction of the proline conformation. Upon adoption of the Chou-Fasman parameters, we are able to derive statistically relevant correlations between the secondary structure of amino acid fragments and the Xaa-Pro peptide bond conformation.

  5. Structure and conformational dynamics of molecules in the excited electronic states: theory and experiment

    International Nuclear Information System (INIS)

    Godunov, I.A.; Bataev, V.A.; Maslov, D.V.; Yakovlev, N.N.

    2017-01-01

    The structure of conformational non-rigid molecules in the excited electronic states are investigated by joint theoretical and experimental methods. The theoretical part of work consist of two stages. In first stage the ab initio quantum-chemical calculations are carried out using high level methods. In second stage the vibrational problems of the various dimensions are solved by variational method for vibrations of large amplitude. In experimental part of work the vibronic spectra are investigated: gas-phase absorption and also, fluorescence excitation spectra of jet-cooled molecules. Some examples are considered.

  6. X-ray structure of the pestivirus NS3 helicase and its conformation in solution.

    Science.gov (United States)

    Tortorici, M Alejandra; Duquerroy, Stéphane; Kwok, Jane; Vonrhein, Clemens; Perez, Javier; Lamp, Benjamin; Bricogne, Gerard; Rümenapf, Till; Vachette, Patrice; Rey, Félix A

    2015-04-01

    Pestiviruses form a genus in the Flaviviridae family of small enveloped viruses with a positive-sense single-stranded RNA genome. Viral replication in this family requires the activity of a superfamily 2 RNA helicase contained in the C-terminal domain of nonstructural protein 3 (NS3). NS3 features two conserved RecA-like domains (D1 and D2) with ATPase activity, plus a third domain (D3) that is important for unwinding nucleic acid duplexes. We report here the X-ray structure of the pestivirus NS3 helicase domain (pNS3h) at a 2.5-Å resolution. The structure deviates significantly from that of NS3 of other genera in the Flaviviridae family in D3, as it contains two important insertions that result in a narrower nucleic acid binding groove. We also show that mutations in pNS3h that rescue viruses from which the core protein is deleted map to D3, suggesting that this domain may be involved in interactions that facilitate particle assembly. Finally, structural comparisons of the enzyme in different crystalline environments, together with the findings of small-angle X-ray-scattering studies in solution, show that D2 is mobile with respect to the rest of the enzyme, oscillating between closed and open conformations. Binding of a nonhydrolyzable ATP analog locks pNS3h in a conformation that is more compact than the closest apo-form in our crystals. Together, our results provide new insight and bring up new questions about pNS3h function during pestivirus replication. Although pestivirus infections impose an important toll on the livestock industry worldwide, little information is available about the nonstructural proteins essential for viral replication, such as the NS3 helicase. We provide here a comparative structural and functional analysis of pNS3h with respect to its orthologs in other viruses of the same family, the flaviviruses and hepatitis C virus. Our studies reveal differences in the nucleic acid binding groove that could have implications for understanding the

  7. High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure.

    Science.gov (United States)

    Rosa-Garrido, Manuel; Chapski, Douglas J; Schmitt, Anthony D; Kimball, Todd H; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J; Ren, Shuxun; Wang, Yibin; Ren, Bing; Vondriska, Thomas M

    2017-10-24

    Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. © 2017 The Authors.

  8. Breaking Dense Structures: Proving Stability of Densely Structured Hybrid Systems

    Directory of Open Access Journals (Sweden)

    Eike Möhlmann

    2015-06-01

    Full Text Available Abstraction and refinement is widely used in software development. Such techniques are valuable since they allow to handle even more complex systems. One key point is the ability to decompose a large system into subsystems, analyze those subsystems and deduce properties of the larger system. As cyber-physical systems tend to become more and more complex, such techniques become more appealing. In 2009, Oehlerking and Theel presented a (de-composition technique for hybrid systems. This technique is graph-based and constructs a Lyapunov function for hybrid systems having a complex discrete state space. The technique consists of (1 decomposing the underlying graph of the hybrid system into subgraphs, (2 computing multiple local Lyapunov functions for the subgraphs, and finally (3 composing the local Lyapunov functions into a piecewise Lyapunov function. A Lyapunov function can serve multiple purposes, e.g., it certifies stability or termination of a system or allows to construct invariant sets, which in turn may be used to certify safety and security. In this paper, we propose an improvement to the decomposing technique, which relaxes the graph structure before applying the decomposition technique. Our relaxation significantly reduces the connectivity of the graph by exploiting super-dense switching. The relaxation makes the decomposition technique more efficient on one hand and on the other allows to decompose a wider range of graph structures.

  9. Dynamical stability in fluid-structure interaction

    International Nuclear Information System (INIS)

    Planchard, J.; Thomas, B.

    1991-01-01

    The aim of the paper is to investigate the dynamical stability of a group of elastic tubes placed in a cross-flow which obeys to the Navier-Stokes equations. The stability of this coupled system is deduced from the study of a quadratic eigenvalue problem arising in the linearized equations. The instability occurs when the real part of one of the eigenvalues becomes positive; the steady state is then replaced by a time-periodic state which is stable (Hopf bifurcation phenomenon). Some numerical methods for solving the quadratic eigenvalue problem are described [fr

  10. Method to planarize three-dimensional structures to enable conformal electrodes

    Science.gov (United States)

    Nikolic, Rebecca J; Conway, Adam M; Graff, Robert T; Reinhardt, Catherine; Voss, Lars F; Shao, Qinghui

    2012-11-20

    Methods for fabricating three-dimensional PIN structures having conformal electrodes are provided, as well as the structures themselves. The structures include a first layer and an array of pillars with cavity regions between the pillars. A first end of each pillar is in contact with the first layer. A segment is formed on the second end of each pillar. The cavity regions are filled with a fill material, which may be a functional material such as a neutron sensitive material. The fill material covers each segment. A portion of the fill material is etched back to produce an exposed portion of the segment. A first electrode is deposited onto the fill material and each exposed segment, thereby forming a conductive layer that provides a common contact to each the exposed segment. A second electrode is deposited onto the first layer.

  11. Theoretical predictor for candidate structure assignment from IMS data of biomolecule-related conformational space.

    Science.gov (United States)

    Schenk, Emily R; Nau, Frederic; Fernandez-Lima, Francisco

    2015-06-01

    The ability to correlate experimental ion mobility data with candidate structures from theoretical modeling provides a powerful analytical and structural tool for the characterization of biomolecules. In the present paper, a theoretical workflow is described to generate and assign candidate structures for experimental trapped ion mobility and H/D exchange (HDX-TIMS-MS) data following molecular dynamics simulations and statistical filtering. The applicability of the theoretical predictor is illustrated for a peptide and protein example with multiple conformations and kinetic intermediates. The described methodology yields a low computational cost and a simple workflow by incorporating statistical filtering and molecular dynamics simulations. The workflow can be adapted to different IMS scenarios and CCS calculators for a more accurate description of the IMS experimental conditions. For the case of the HDX-TIMS-MS experiments, molecular dynamics in the "TIMS box" accounts for a better sampling of the molecular intermediates and local energy minima.

  12. Photo-stability study of a solution-processed small molecule solar cell system: correlation between molecular conformation and degradation.

    Science.gov (United States)

    Newman, Michael J; Speller, Emily M; Barbé, Jérémy; Luke, Joel; Li, Meng; Li, Zhe; Wang, Zhao-Kui; Jain, Sagar M; Kim, Ji-Seon; Lee, Harrison Ka Hin; Tsoi, Wing Chung

    2018-01-01

    Solution-processed organic small molecule solar cells (SMSCs) have achieved efficiency over 11%. However, very few studies have focused on their stability under illumination and the origin of the degradation during the so-called burn-in period. Here, we studied the burn-in period of a solution-processed SMSC using benzodithiophene terthiophene rhodamine:[6,6]-phenyl C 71 butyric acid methyl ester (BTR:PC 71 BM) with increasing solvent vapour annealing time applied to the active layer, controlling the crystallisation of the BTR phase. We find that the burn-in behaviour is strongly correlated to the crystallinity of BTR. To look at the possible degradation mechanisms, we studied the fresh and photo-aged blend films with grazing incidence X-ray diffraction, UV-vis absorbance, Raman spectroscopy and photoluminescence (PL) spectroscopy. Although the crystallinity of BTR affects the performance drop during the burn-in period, the degradation is found not to originate from the crystallinity changes of the BTR phase, but correlates with changes in molecular conformation - rotation of the thiophene side chains, as resolved by Raman spectroscopy which could be correlated to slight photobleaching and changes in PL spectra.

  13. Enhanced photoelectrochemical efficiency and stability using a conformal TiO2 film on a black silicon photoanode

    Science.gov (United States)

    Yu, Yanhao; Zhang, Zheng; Yin, Xin; Kvit, Alexander; Liao, Qingliang; Kang, Zhuo; Yan, Xiaoqin; Zhang, Yue; Wang, Xudong

    2017-06-01

    Black silicon (b-Si) is a surface-nanostructured Si with extremely efficient light absorption capability and is therefore of interest for solar energy conversion. However, intense charge recombination and low electrochemical stability limit the use of b-Si in photoelectrochemical solar-fuel production. Here we report that a conformal, ultrathin, amorphous TiO2 film deposited by low-temperature atomic layer deposition (ALD) on top of b-Si can simultaneously address both of these issues. Combined with a Co(OH)2 thin film as the oxygen evolution catalyst, this b-Si/TiO2/Co(OH)2 heterostructured photoanode was able to produce a saturated photocurrent density of 32.3 mA cm-2 at an external potential of 1.48 V versus reversible reference electrode (RHE) in 1 M NaOH electrolyte. The enhanced photocurrent relative to planar Si and unprotected b-Si photoelectrodes was attributed to the enhanced charge separation efficiency as a result of the effective passivation of defective sites on the b-Si surface. The 8-nm ALD TiO2 layer extends the operational lifetime of b-Si from less than half an hour to four hours.

  14. Aggregation and conformational stability evaluation of myoglobin in the presence of ionic surfactant

    Directory of Open Access Journals (Sweden)

    Mohammad A. Alsenaidy

    2018-05-01

    Full Text Available Sodium lauroyl sarcosinate (SLS is frequently used for the solubilization of inclusion bodies in vitro due to its structural similarity to lipid plasma membrane. There are many factors that could influence protein aggregation propensity, including overall protein surface charge and hydrophobicity. Here, the aggregation pathway of myoglobin protein was studied under different conditions (pH 3.5 and 7.4 in the presence of varying concentrations of SLS to evaluate the underlying forces dictating protein aggregation. Data obtained from Rayleigh light scattering, ThT binding assay, and far-UV CD indicated that SLS have different effects on the protein depending on its concentration and environmental conditions. In the presence of low concentrations of SLS (0.05–0.1 mM, no aggregation was detected at both pH conditions tested. Whereas, as we reach higher SLS concentrations (0.5–10.0 mM, myoglobin started forming larger-sized aggregates at pH 3.5 and not pH 7.4. These results suggest that electrostatics interactions as well as hydrophobic forces play an important role in SLS-induced myoglobin aggregation. Keywords: Sodium lauroyl sarcosinate, Surfactant, Myoglobin, Protein aggregation, Amorphous aggregates, pH

  15. Structure and thermal stability of nanocrystalline materials

    Indian Academy of Sciences (India)

    In addition, study of the thermal stability of nanocrystalline materials against significant grain growth is both scientific and technological interest. A sharp increase in grain size (to micron levels) during consolidation of nanocrystalline powders to obtain fully dense materials may consequently result in the loss of some unique ...

  16. Non-Watson-Crick structures in oligodeoxynucleotides: Self-association of d(TpCpGpA) stabilized at acidic pH

    International Nuclear Information System (INIS)

    Topping, R.J.; Stone, M.P.; Brush, C.K.; Harris, T.M.

    1988-01-01

    The 1 H NMR spectrum of the tetradeoxynucleotide d(TpCpGpA) was examined as a function of temperature, pH, and concentration. At pH 7 and above the solution conformation for this oligodeoxynucleotide appears to be a mixture of random coil and Watson-Crick duplex. At 25 degree C, a pH titration of d(TpCpGaA) shown that distinct conformational changes occur as the pH is lowered below 7.0. These conformational changes are reversible upon readjusting the pH to neutrality, indicating the presence of a pH-dependent set of conformational equilibria. At 25 degree C, the various conformational state in the mixture are in rapid exchange on the NMR time scale. Examination of the titration curve shown the presence of distinct conformational states at pH greater than 7, and between pH 4 and pH 5. When the pH titration is repeated at 5 degree C, the conformational equilibria are in slow exchange on the NMR time scale; distinct signals from each conformational state are observable. The stable conformational state present between pH 4 and pH 5 represents an ordered conformation of d(TpCpGpA) which dissociates to a less ordered structure upon raising the temperature. The ordered conformation differs from the Watson-Crick helix, as is shown from nuclear Overhauser enhancement experiments, as well as chemical shift data. These results indicate that their ordered conformation is similar to the conformation of d(TpCpGpA) observed between pH 4 and pH 5. In the present case it is likely that stabilization of an ordered duplex conformation for d(TpCpGpA) is achieved by protonation of cytosine. A possible model which could explain the data involves formation of Hoogsteen C + :G base pairs

  17. Epothilones as lead structures for the synthesis-based discovery of new chemotypes for microtubule stabilization.

    Science.gov (United States)

    Feyen, Fabian; Cachoux, Frédéric; Gertsch, Jürg; Wartmann, Markus; Altmann, Karl-Heinz

    2008-01-01

    Epothilones are macrocyclic bacterial natural products with potent microtubule-stabilizing and antiproliferative activity. They have served as successful lead structures for the development of several clinical candidates for anticancer therapy. However, the structural diversity of this group of clinical compounds is rather limited, as their structures show little divergence from the original natural product leads. Our own research has explored the question of whether epothilones can serve as a basis for the development of new structural scaffolds, or chemotypes, for microtubule stabilization that might serve as a basis for the discovery of new generations of anticancer drugs. We have elaborated a series of epothilone-derived macrolactones whose overall structural features significantly deviate from those of the natural epothilone scaffold and thus define new structural families of microtubule-stabilizing agents. Key elements of our hypermodification strategy are the change of the natural epoxide geometry from cis to trans, the incorporation of a conformationally constrained side chain, the removal of the C3-hydroxyl group, and the replacement of C12 with nitrogen. So far, this approach has yielded analogs 30 and 40 that are the most advanced, the most rigorously modified, structures, both of which are potent antiproliferative agents with low nanomolar activity against several human cancer cell lines in vitro. The synthesis was achieved through a macrolactone-based strategy or a high-yielding RCM reaction. The 12-aza-epothilone ("azathilone" 40) may be considered a "non-natural" natural product that still retains most of the overall structural characteristics of a true natural product but is structurally unique, because it lies outside of the general scope of Nature's biosynthetic machinery for polyketide synthesis. Like natural epothilones, both 30 and 40 promote tubulin polymerization in vitro and at the cellular level induce cell cycle arrest in mitosis. These

  18. Stereoselectivity and conformational stability of haloalkane dehalogenase DbjA from Bradyrhizobium japonicum USDA110: the effect of pH and temperature.

    Science.gov (United States)

    Chaloupkova, Radka; Prokop, Zbynek; Sato, Yukari; Nagata, Yuji; Damborsky, Jiri

    2011-08-01

    The effect of pH and temperature on structure, stability, activity and enantioselectivity of haloalkane dehalogenase DbjA from Bradyrhizobium japonicum USDA110 was investigated in this study. Conformational changes have been assessed by circular dichroism spectroscopy, functional changes by kinetic analysis, while quaternary structure was studied by gel filtration chromatography. Our study shows that the DbjA enzyme is highly tolerant to pH changes. Its secondary and tertiary structure was not affected by pH in the ranges 5.3-10.3 and 6.2-10.1, respectively. Oligomerization of DbjA was strongly pH-dependent: monomer, dimer, tetramer and a high molecular weight cluster of the enzyme were distinguished in solution at different pH conditions. Moreover, different oligomeric states of DbjA possessed different thermal stabilities. The highest melting temperature (T(m) = 49.1 ± 0.2 °C) was observed at pH 6.5, at which the enzyme occurs in dimeric form. Maximal activity was detected at 50 °C and in the pH interval 7.7-10.4. While pH did not have any effect on enantiodiscriminination of DbjA, temperature significantly altered DbjA enantioselectivity. A decrease in temperature results in significantly enhanced enantioselectivity. The temperature dependence of DbjA enantioselectivity was analysed with 2-bromobutane, 2-bromopentane, methyl 2-bromopropionate and ethyl 2-bromobutyrate, and differential activation parameters Δ(R-S)ΔH and Δ(R-S)ΔS were determined. The thermodynamic analysis revealed that the resolution of β-bromoalkanes was driven by both enthalpic and entropic terms, while the resolution of α-bromoesters was driven mainly by an enthalpic term. Unique catalytic activity and structural stability of DbjA in a broad pH range, combined with high enantioselectivity with particular substrates, make this enzyme a very versatile biocatalyst. Enzyme EC3.8.1.5 haloalkane dehalogenase. © 2011 The Authors Journal compilation © 2011 FEBS.

  19. Advances in Computational Stability Analysis of Composite Aerospace Structures

    International Nuclear Information System (INIS)

    Degenhardt, R.; Araujo, F. C. de

    2010-01-01

    European aircraft industry demands for reduced development and operating costs. Structural weight reduction by exploitation of structural reserves in composite aerospace structures contributes to this aim, however, it requires accurate and experimentally validated stability analysis of real structures under realistic loading conditions. This paper presents different advances from the area of computational stability analysis of composite aerospace structures which contribute to that field. For stringer stiffened panels main results of the finished EU project COCOMAT are given. It investigated the exploitation of reserves in primary fibre composite fuselage structures through an accurate and reliable simulation of postbuckling and collapse. For unstiffened cylindrical composite shells a proposal for a new design method is presented.

  20. A molecular modeling approach to understand the structure and conformation relationship of (GlcpA)Xylan.

    Science.gov (United States)

    Guo, Qingbin; Kang, Ji; Wu, Yan; Cui, Steve W; Hu, Xinzhong; Yada, Rickey Y

    2015-12-10

    The structure and conformation relationships of a heteropolysaccharide (GlcpA)Xylan in terms of various molecular weights, Xylp/GlcpA ratio and the distribution of GlcpA along xylan chain were investigated using computer modeling. The adiabatic contour maps of xylobiose, XylpXylp(GlcpA) and (GlcpA)XylpXylp(GlcpA) indicated that the insertion of the side group (GlcpA) influenced the accessible conformational space of xylobiose molecule. RIS-Metropolis Monte Carlo method indicated that insertion of GlcpA side chain induced a lowering effect of the calculated chain extension at low GlcpA:Xylp ratio (GlcpA:Xylp = 1:3). The chain, however, became extended when the ratio of GlcpA:Xylp above 2/3. It was also shown that the spatial extension of the polymer chains was dependent on the distribution of side chain: the random distribution demonstrated the most flexible structure compared to block and alternative distribution. The present studies provide a unique insight into the dependence of both side chain ratio and distribution on the stiffness and flexibility of various (GlcpA)Xylan molecules. Copyright © 2015. Published by Elsevier Ltd.

  1. Silver ions-mediated conformational switch: facile design of structure-controllable nucleic acid probes.

    Science.gov (United States)

    Wang, Yongxiang; Li, Jishan; Wang, Hao; Jin, Jianyu; Liu, Jinhua; Wang, Kemin; Tan, Weihong; Yang, Ronghua

    2010-08-01

    Conformationally constraint nucleic acid probes were usually designed by forming an intramolecular duplex based on Watson-Crick hydrogen bonds. The disadvantages of these approaches are the inflexibility and instability in complex environment of the Watson-Crick-based duplex. We report that this hydrogen bonding pattern can be replaced by metal-ligation between specific metal ions and the natural bases. To demonstrate the feasibility of this principle, two linear oligonucleotides and silver ions were examined as models for DNA hybridization assay and adenosine triphosphate detection. The both nucleic acids contain target binding sequences in the middle and cytosine (C)-rich sequences at the lateral portions. The strong interaction between Ag(+) ions and cytosines forms stable C-Ag(+)-C structures, which promises the oligonucleotides to form conformationally constraint formations. In the presence of its target, interaction between the loop sequences and the target unfolds the C-Ag(+)-C structures, and the corresponding probes unfolding can be detected by a change in their fluorescence emission. We discuss the thermodynamic and kinetic opportunities that are provided by using Ag(+) ion complexes instead of traditional Watson-Crick-based duplex. In particular, the intrinsic feature of the metal-ligation motif facilitates the design of functional nucleic acids probes by independently varying the concentration of Ag(+) ions in the medium.

  2. Stability, structure, and evolution of cool loops

    International Nuclear Information System (INIS)

    Cally, P.S.; Robb, T.D.

    1991-01-01

    The criteria for the existence and stability of cool loops are reexamined. It is found that the stability of the loops strongly depends on the form of the heating and radiative loss functions and that if the Ly-alpha peak which appears in most calculations of the radiative loss function is real, cool loops are almost certainly unstable. Removing the hydrogen contribution from the recent loss function Q(T) by Cook et al. (1989) does not produce the much-used result, Q proportional to T-cubed, which is so favorable to cool loop stability. Even using the probably unrealistically favorable loss function Q1 of Cook et al. with the hydrogen contribution removed, the maximum temperature attainable in stable cool loops is a factor of 2-3 too small to account for the excess emission observed in lower transition region lines. Dynamical simulations of cool loop instabilities reveal that the final state of such a model is the hot loop equilibrium. 26 refs

  3. Structure and conformational analysis of spiroketals from 6-O-methyl-9(E-hydroxyiminoerythronolide A

    Directory of Open Access Journals (Sweden)

    Ana Čikoš

    2015-08-01

    Full Text Available Three novel spiroketals were prepared by a one-pot transformation of 6-O-methyl-9(E-hydroxyiminoerythronolide A. We present the formation of a [4.5]spiroketal moiety within the macrolide lactone ring, but also the unexpected formation of a 10-C=11-C double bond and spontaneous change of stereochemistry at position 8-C. As a result, a thermodynamically stable structure was obtained. The structures of two new diastereomeric, unsaturated spiroketals, their configurations and conformations, were determined by means of NMR spectroscopy and molecular modelling. The reaction kinetics and mechanistic aspects of this transformation are discussed. These rearrangements provide a facile synthesis of novel macrolide scaffolds.

  4. Structure, conformation in aqueous solution and antimicrobial activity of ulvan extracted from green seaweed Ulva reticulata.

    Science.gov (United States)

    Tran, Thi Thanh Van; Truong, Hai Bang; Tran, Nguyen Ha Vy; Quach, Thi Minh Thu; Nguyen, Thi Nu; Bui, Minh Ly; Yuguchi, Yoshiaki; Thanh, Thi Thu Thuy

    2017-12-04

    The aim of this study is to elucidate the structure and investigate the antimicrobial activity of an ulvan obtained by water extraction from green seaweed Ulva reticulata collected at Nha Trang sea of Vietnam by using IR, NMR, SEC-MALLS and SAXS methods. The ulvan is composed of rhamnose, galactose, xylose, manose and glucose (mole ratio Rha: Gal: Xyl: Man: Glu = 1:0.12:0.1:0.06:0.03), uronic acid (22.5%) and sulphate groups (17.6%). Chemically structural determination showed that the ulvan mainly composed of disaccharide [→4)β-D-GlcA(1→4)α-L-Rha3S-(1→]. The results from SAXS indicated that ulvan under study has a rod-like bulky chain conformation. Ulvan from U. reticulata showed high antimicrobial activity, with inhibition zone diameter of 20 mm against Enterobacter cloace and 18 mm against Escherichia coli.

  5. Conformational analysis of an acyclic tetrapeptide: ab-initio structure determination from X-ray powder diffraction, Hirshfeld surface analysis and electronic structure.

    Science.gov (United States)

    Das, Uday; Naskar, Jishu; Mukherjee, Alok Kumar

    2015-12-01

    A terminally protected acyclic tetrapeptide has been synthesized, and the crystal structure of its hydrated form, Boc-Tyr-Aib-Tyr-Ile-OMe·2H2O (1), has been determined directly from powder X-ray diffraction data. The backbone conformation of tetrapeptide (1) exhibiting two consecutive β-turns is stabilized by two 4 → 1 intramolecular N-H · · · O hydrogen bonds. In the crystalline state, the tetrapeptide molecules are assembled through water-mediated O-H · · · O hydrogen bonds to form two-dimensional molecular sheets, which are further linked by intermolecular C-H · · · O hydrogen bonds into a three-dimensional supramolecular framework. The molecular electrostatic potential (MEP) surface of (1) has been used to supplement the crystallographic observations. The nature of intermolecular interactions in (1) has been analyzed quantitatively through the Hirshfeld surface and two-dimensional fingerprint plot. The DFT optimized molecular geometry of (1) agrees closely with that obtained from the X-ray structure analysis. The present structure analysis of Boc-Tyr-Aib-Tyr-Ile-OMe·2H2 O (1) represents a case where ab-initio crystal structure of an acyclic tetrapeptide with considerable molecular flexibility has been accomplished from laboratory X-ray powder diffraction data. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  6. On One Approach to TSP Structural Stability

    Directory of Open Access Journals (Sweden)

    Evgeny Ivanko

    2014-01-01

    Full Text Available In this paper we study an inverse approach to the traveling salesman reoptimization problem. Namely, we consider the case of the addition of a new vertex to the initial TSP data and fix the simple “adaptation” algorithm: the new vertex is inserted into an edge of the optimal tour. In the paper we consider the conditions describing the vertexes that can be inserted by this algorithm without loss of optimality, study the properties of stability areas, and address several model applications.

  7. Electronic structure theory of alloy phase stability

    International Nuclear Information System (INIS)

    Turchi, P.E.A.; Sluiter, M.

    1992-01-01

    We present a brief overview of the advanced methodology which has been developed and applied to the study of phase stability properties in substitutional alloys. The approach is based on the real space version of the Generalized Perturbation Method within the Korringa-Kohn-Rostoker multiple scattering formulation of the Coherent Potential Approximation. Temperature effects are taken into account with a generalized meanfield approach, namely the Cluster Variation Method, or with Monte-Carlo simulations. We show that this approach is well suited for studying ground state properties of substitutional alloys, for calculating energies of idealized interfaces and antiphase boundaries, and finally to compute alloy phase diagrams

  8. Rock stream stability structures in the vicinity of bridges.

    Science.gov (United States)

    2014-10-01

    This report was sponsored by the Utah Department of Transportation (UDOT) to determine if rock stream stability structures could be used as : scour countermeasures and to protect streambanks. Traditional scour countermeasures, such as rock riprap, ar...

  9. Structure and stability of warm cores in neutron stars

    Energy Technology Data Exchange (ETDEWEB)

    Ibanez Cabanell, J M [Departamento de Mecanica y Astronomia, Facultad de Matematicas, Burjasot-Valencia (Spain)

    1981-12-01

    Relativistic equations of structure are solved using Lamb's equations of state for warm neutron degenerate matter. The stability of isothermal cores in neutron stars is discussed and also the possible compatibility of the results obtained with experimental evidence is shown.

  10. Interface stability of granular filter structures under currents

    NARCIS (Netherlands)

    Verheij, H.J.; Hoffmans, G.; Dorst, K.; Van de Sande, S.

    2012-01-01

    Granular filters are used for protection of structures against scour and erosion. For a proper functioning it is necessary that the interfaces between the filter structure, the subsoil and the water flowing above the filter structure are stable. Stability means that there is no transport of subsoil

  11. Understanding structure-stability relationships of Candida antartica lipase B in ionic liquids.

    Science.gov (United States)

    De Diego, Teresa; Lozano, Pedro; Gmouh, Said; Vaultier, Michel; Iborra, José L

    2005-01-01

    Two different water-immiscible ionic liquids (ILs), 1-ethyl-3-methylimidizolium bis(trifluoromethylsulfonyl)imide and butyltrimethylammonium bis(trifluoromethylsulfonyl)imide, were used for butyl butyrate synthesis from vinyl butyrate catalyzed by Candida antarctica lipase B (CALB) at 2% (v/v) water content and 50 degrees C. Both the synthetic activity and stability of the enzyme in these ILs were enhanced as compared to those in hexane. Circular dichroism and intrinsic fluorescence spectroscopic techniques have been used over a period of 4 days to determine structural changes in the enzyme associated with differences in its stability for each assayed medium. CALB showed a loss in residual activity higher than 75% after 4 days of incubation in both water and hexane media at 50 degrees C, being related to great changes in both alpha-helix and beta-strand secondary structures. The stabilization of CALB, which was observed in the two ILs studied, was associated with both the maintenance of the 50% of initial alpha-helix content and the enhancement of beta-strands. Furthermore, intrinsic fluorescence studies clearly showed how a classical enzyme unfolding was occurring with time in both water and hexane media. However, the structural changes associated with the incubation of the enzyme in both ILs might be attributed to a compact and active enzyme conformation, resulting in an enhancement of the stability in these nonaqueous environments.

  12. Stability patterns for a size-structured population model and its stage-structured counterpart

    DEFF Research Database (Denmark)

    Zhang, Lai; Pedersen, Michael; Lin, Zhigui

    2015-01-01

    In this paper we compare a general size-structured population model, where a size-structured consumer feeds upon an unstructured resource, to its simplified stage-structured counterpart in terms of equilibrium stability. Stability of the size-structured model is understood in terms of an equivale...... to the population level....

  13. Human serum albumin as protecting agent of silver nanoparticles: role of the protein conformation and amine groups in the nanoparticle stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Alarcon, Emilio I.; Bueno-Alejo, Carlos J.; Noel, Christopher W.; Stamplecoskie, Kevin G. [Centre for Catalysis Research and Innovation, University of Ottawa, Department of Chemistry (Canada); Pacioni, Natalia L. [Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, INFIQC, Departamento de Quimica Organica (Argentina); Poblete, Horacio [Center for Bioinformatics and Molecular Simulations, Universidad de Talca (Chile); Scaiano, J. C., E-mail: tito@photo.chem.uottawa.ca [Centre for Catalysis Research and Innovation, University of Ottawa, Department of Chemistry (Canada)

    2013-01-15

    Thermally denatured human serum albumin interacts with {approx}3.0 nm spherical AgNP enhancing the fluorescence of Trp-214 at large protein/nanoparticle ratios. However, using native HSA, no changes in the emission were observed. The observation is likely due to differences between native and denatured protein packing resulting from protein corona formation. We have also found that NH{sub 2} blocking of the protein strongly affects the ability of the protein to protect AgNP from different salts/ions such as NaCl, PBS, Hank's buffer, Tris-HCl, MES, and DMEM. Additionally, AgNP can be readily prepared in aqueous solutions by a photochemical approach employing HSA as an in situ protecting agent. The role of the protein in this case is beyond that of protecting agent; thus, Ag{sup +} ions and I-2959 complexation within the protein structure also affects the efficiency of AgNP formation. Blocking NH{sub 2} in HSA modified the AgNP growth profile, surface plasmon band shape, and long-term stability suggesting that amine groups are directly involved in the formation and post-stabilization of AgNP. In particular, AgNP size and shape are extensively influenced by NH{sub 2} blocking, leading primarily to cubes and plates with sizes around 5-15 nm; in contrast, spherical monodisperse 4.0 nm AgNP are observed for native HSA. The nanoparticles prepared by this protocol are non-toxic in primary cells and have remarkable antibacterial properties. Finally, surface plasmon excitation of native HSA-AgNP promoted loss of protein conformation in just 5 min, suggesting that plasmon heating causes protein denaturation using continuous light sources such as commercial LED.

  14. Human serum albumin as protecting agent of silver nanoparticles: role of the protein conformation and amine groups in the nanoparticle stabilization

    International Nuclear Information System (INIS)

    Alarcon, Emilio I.; Bueno-Alejo, Carlos J.; Noel, Christopher W.; Stamplecoskie, Kevin G.; Pacioni, Natalia L.; Poblete, Horacio; Scaiano, J. C.

    2013-01-01

    Thermally denatured human serum albumin interacts with ∼3.0 nm spherical AgNP enhancing the fluorescence of Trp-214 at large protein/nanoparticle ratios. However, using native HSA, no changes in the emission were observed. The observation is likely due to differences between native and denatured protein packing resulting from protein corona formation. We have also found that NH 2 blocking of the protein strongly affects the ability of the protein to protect AgNP from different salts/ions such as NaCl, PBS, Hank’s buffer, Tris–HCl, MES, and DMEM. Additionally, AgNP can be readily prepared in aqueous solutions by a photochemical approach employing HSA as an in situ protecting agent. The role of the protein in this case is beyond that of protecting agent; thus, Ag + ions and I-2959 complexation within the protein structure also affects the efficiency of AgNP formation. Blocking NH 2 in HSA modified the AgNP growth profile, surface plasmon band shape, and long-term stability suggesting that amine groups are directly involved in the formation and post-stabilization of AgNP. In particular, AgNP size and shape are extensively influenced by NH 2 blocking, leading primarily to cubes and plates with sizes around 5–15 nm; in contrast, spherical monodisperse 4.0 nm AgNP are observed for native HSA. The nanoparticles prepared by this protocol are non-toxic in primary cells and have remarkable antibacterial properties. Finally, surface plasmon excitation of native HSA-AgNP promoted loss of protein conformation in just 5 min, suggesting that plasmon heating causes protein denaturation using continuous light sources such as commercial LED.

  15. Phase stability and electronic structure of transition-metal aluminides

    International Nuclear Information System (INIS)

    Carlsson, A.E.

    1992-01-01

    This paper will describe the interplay between die electronic structure and structural energetics in simple, complex, and quasicrystalline Al-transition metal (T) intermetallics. The first example is the Ll 2 -DO 22 competition in Al 3 T compounds. Ab-initio electronic total-energy calculations reveal surprisingly large structural-energy differences, and show that the phase stability of both stoichiometric and ternary-substituted compounds correlates closely with a quasigap in the electronic density of states (DOS). Secondly, ab-initio calculations for the structural stability of the icosahedrally based Al 12 W structure reveal similar quasigap effects, and provide a simple physical explanation for the stability of the complex aluminide structures. Finally, parametrized tight-binding model calculations for the Al-Mn quasicrystal reveal a large spread in the local Mn DOS behavior, and support a two-site model for the quasicrystal's magnetic behavior

  16. Ab initio Hartree-Fock and density functional theory investigations on the conformational stability, molecular structure and vibrational spectra of 5-chloro-3-(2-(4-methylpiperazin-1-yl)-2-oxoethyl)benzo[d]thiazol-2(3H)-one drug molecule.

    Science.gov (United States)

    Taşal, Erol; Kumalar, Mustafa

    2012-09-01

    In this work, the experimental and theoretical spectra of 5-chloro-3-(2-(4-methylpiperazin-1-yl)-2-oxoethyl)benzo[d]thiazol-2(3H)-one molecule (abbreviated as 5CMOT) are studied. The molecular geometry and vibrational frequencies are calculated in the ground state of molecule using ab initio Hartree-Fock (HF) and Density Function Theory (DFT) methods with 6-311++G(d,p), 6-31G++(d,p), 6-31G(d,p), 6-31G(d) and 6-31G basis sets. Three staggered stable conformers were observed on the torsional potential energy surfaces. The complete assignments were performed on the basis of the total energy distribution (TED) of the vibrational modes calculated. The comparison of the theoretical and experimental geometries of the title compound indicated that the X-ray parameters fairly well agree with the theoretically obtained values for the most stable conformer. The theoretical results showed an excellent agreement with the experimental values. The calculated HOMO and LUMO energies show that the charge transfer occurs within the molecule. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Structuring Economic Power for Stability Operations

    National Research Council Canada - National Science Library

    Wallen, Andrew T

    2006-01-01

    .... By their nature, these operations have a strong economic context. This thesis provides a methodology for evaluating current institutional structures and economic doctrines being forged among various government agencies...

  18. Retrieving transient conformational molecular structure information from inner-shell photoionization of laser-aligned molecules

    Science.gov (United States)

    Wang, Xu; Le, Anh-Thu; Yu, Chao; Lucchese, R. R.; Lin, C. D.

    2016-01-01

    We discuss a scheme to retrieve transient conformational molecular structure information using photoelectron angular distributions (PADs) that have averaged over partial alignments of isolated molecules. The photoelectron is pulled out from a localized inner-shell molecular orbital by an X-ray photon. We show that a transient change in the atomic positions from their equilibrium will lead to a sensitive change in the alignment-averaged PADs, which can be measured and used to retrieve the former. Exploiting the experimental convenience of changing the photon polarization direction, we show that it is advantageous to use PADs obtained from multiple photon polarization directions. A simple single-scattering model is proposed and benchmarked to describe the photoionization process and to do the retrieval using a multiple-parameter fitting method. PMID:27025410

  19. Structural and Conformational Chemistry from Electrochemical Molecular Machines. Replicating Biological Functions. A Review.

    Science.gov (United States)

    Otero, Toribio F

    2017-12-14

    Each constitutive chain of a conducting polymer electrode acts as a reversible multi-step electrochemical molecular motor: reversible reactions drive reversible conformational movements of the chain. The reaction-driven cooperative actuation of those molecular machines generates, or destroys, inside the film the free volume required to lodge/expel balancing counterions and solvent: reactions drive reversible film volume variations, which basic structural components are here identified and quantified from electrochemical responses. The content of the reactive dense gel (chemical molecular machines, ions and water) mimics that of the intracellular matrix in living functional cells. Reaction-driven properties (composition-dependent properties) and devices replicate biological functions and organs. An emerging technological world of soft, wet, reaction-driven, multifunctional and biomimetic devices and the concomitant zoomorphic or anthropomorphic robots is presented. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. The Structure of Nuclei Far from Stability

    International Nuclear Information System (INIS)

    Zganjar, E.F.

    1999-01-01

    From among a number of important nuclear structure results that have emerged from our research program during the past few years, two stand out as being of extra significance. These are: (a) the identification of a diabatic coexisting structure in 187 Au which arises solely from differences in proton occupation of adjacent oscillator shells, and (b) the realization of a method for estimating EO strength in nuclei and the resulting prediction that the de-excitation of superdeformed bands may proceed, in some cases, by strong EO transitions

  1. Atomistic mechanisms governing structural stability change of zinc antimony thermoelectrics

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaolong [Frontier Institute of Science and Technology, Xi' an Jiaotong University, Xi' an 710054 (China); Lin, Jianping, E-mail: jaredlin@163.com [School of Materials Science and Engineering, Xiamen University of Technology, Xiamen 361024 (China); Qiao, Guanjun [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Wang, Zhao, E-mail: zwangzhao@gmail.com [Frontier Institute of Science and Technology, Xi' an Jiaotong University, Xi' an 710054 (China); State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China)

    2015-01-05

    The structural stability of thermoelectric materials is a subject of growing importance for their energy harvesting applications. Here, we study the microscopic mechanisms governing the structural stability change of zinc antimony at its working temperature, using molecular dynamics combined with experimental measurements of the electrical and thermal conductivity. Our results show that the temperature-dependence of the thermal and electrical transport coefficients is strongly correlated with a structural transition. This is found to be associated with a relaxation process, in which a group of Zn atoms migrates between interstitial sites. This atom migration gradually leads to a stabilizing structural transition of the entire crystal framework, and then results in a more stable crystal structure of β–Zn{sub 4}Sb{sub 3} at high temperature.

  2. Comparison of NMR and crystal structures highlights conformational isomerism in protein active sites

    International Nuclear Information System (INIS)

    Serrano, Pedro; Pedrini, Bill; Geralt, Michael; Jaudzems, Kristaps; Mohanty, Biswaranjan; Horst, Reto; Herrmann, Torsten; Elsliger, Marc-André; Wilson, Ian A.; Wüthrich, Kurt

    2010-01-01

    Tools for systematic comparisons of NMR and crystal structures developed by the JCSG were applied to two proteins with known functions: the T. maritima anti-σ factor antagonist TM1081 and the mouse γ-glutamylamine cyclotransferase A2LD1 (gi:13879369). In an attempt to exploit the complementarity of crystal and NMR data, the combined use of the two structure-determination techniques was explored for the initial steps in the challenge of searching proteins of unknown functions for putative active sites. The JCSG has recently developed a protocol for systematic comparisons of high-quality crystal and NMR structures of proteins. In this paper, the extent to which this approach can provide function-related information on the two functionally annotated proteins TM1081, a Thermotoga maritima anti-σ factor antagonist, and A2LD1 (gi:13879369), a mouse γ-glutamylamine cyclotransferase, is explored. The NMR structures of the two proteins have been determined in solution at 313 and 298 K, respectively, using the current JCSG protocol based on the software package UNIO for extensive automation. The corresponding crystal structures were solved by the JCSG at 100 K and 1.6 Å resolution and at 100 K and 1.9 Å resolution, respectively. The NMR and crystal structures of the two proteins share the same overall molecular architectures. However, the precision of the structure determination along the amino-acid sequence varies over a significantly wider range in the NMR structures than in the crystal structures. Thereby, in each of the two NMR structures about 65% of the residues have displacements below the average and in both proteins the less well ordered residues include large parts of the active sites, in addition to some highly solvent-exposed surface areas. Whereas the latter show increased disorder in the crystal and in solution, the active-site regions display increased displacements only in the NMR structures, where they undergo local conformational exchange on the

  3. Structural stability of nano-sized clusters

    NARCIS (Netherlands)

    De Hosson, JTM; Palasantzas, G; Vystavel, T; Koch, S; Ovidko,; Pande, CS; Krishnamoorti, R; Lavernia, E; Skandan, G

    2004-01-01

    This contribution presents challenges to control the microstructure in nano-structured materials via a relatively new approach, i.e. using a so-called nanocluster source. An important aspect is that the cluster size distribution is monodisperse and that the kinetic energy of the clusters during

  4. Structural stability properties of Friedman cosmology

    International Nuclear Information System (INIS)

    Szydlowski, M.; Heller, M.; Pontificial Academy of Cracow, Krakow; Golda, Z.

    1984-01-01

    A dynamical system with Robertson-Walker symmetries and the equation of the state p = γepsilon, O <= γ <= 1, considered both as a conservative and nonconservative system, is studied with respect to its structural properties. Different cases are shown and analyzed on the phase space (x = Rsup(D), γ = (dx/dt)). (author)

  5. A study of the conformation and stability of nitroxide free radicals; Etude de la conformation et de la stabilite de radicaux libres nitroxydes

    Energy Technology Data Exchange (ETDEWEB)

    Briere, R [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1969-03-01

    The first part of this study is an application of nuclear magnetic resonance to the determination of the sign and magnitude of the long range nuclear-electron spin-spin couplings in the free radical nitroxide derived from piperidine. It has been shown that the coupling constants of the protons {gamma} to the nitrogen atom have a pronounced spatial dependence as do the protons in the {beta} position, a point which has not been brought out by previous investigations. Conformational analysis of these compounds has been carried out by measurement of the effect of temperature on the NMR spectra at 310 MHz. The synthesis of di-t-Bu nitroxide labelled with C{sup 13} in the {alpha}-position made possible the unambiguous determination of the corresponding {sup 13}C nuclear-electron spin-spin coupling constant, a parameter which had not previously been measured. The coupling constants measured in the 2,2,6,6-tetramethyl piperidine series could then be attributed to the {sup 13}C atoms in the {beta}-position and their variation related to the conformations of the heterocycles. This constitutes the second part of the work reported here. The final section is devoted to a study of the decomposition of an unstable nitroxide having a hydrogen atom in the p-position. This decomposition is bimolecular and the primary isotope effect shows that the rupture. of the C-H bond is involved. From this one can conclude that a nitroxide is stable when the different groups attached to the nitrogen atom cannot give rise to a decomposition either intra molecularly, if the molecular geometry is suitable, or inter molecularly by dimerisation through attack on a different center of a neighbouring molecule thus leading to a fragmentation or a disproportionation. (author) [French] La premiere partie est une application de la resonance magnetique nucleaire a la determination du signe et de la grandeur des couplages a longue distance dans des radicaux libres nitroxydes piperidiniques. Il est montre que

  6. FINANCIAL SYSTEM STRUCTURE AND STABILITY DURING TRANSITION

    Directory of Open Access Journals (Sweden)

    Firtescu Bogdan

    2012-07-01

    Full Text Available The process of transition from socialist economy to market economy was not considered an end in itself, but a necessity, and standing proof to achieve high levels of sustainable development. All former socialist countries are characterized by an early transition recession transformation result of the restructuring, loss of markets, tough competition from foreign products, best quality, or in other cases cheaper. To express the financial system structure in transition we take into discussion data that reflects representatives mutations and restructuring in Central and Eastern European countries, such Bulgaria, Czech Republic, Hungary, Poland and Romania. For all countries we show some important changes of financial system during transition and construct an image matrix that illustrates important indicators of financial system structure and their adjustment.

  7. Nuclear structure/nuclei far from stability

    International Nuclear Information System (INIS)

    Casten, R.F.; Garrett, J.D.; Moller, P.; Bauer, W.W.; Brenner, D.S.; Butler, G.W.; Crawford, J.E.; Davids, C.N.; Dyer, P.L.; Gregorich, K.; Hagbert, E.G.; Hamilton, W.D.; Harar, S.; Haustein, P.E.; Hayes, A.C.; Hoffman, D.C.; Hsu, H.H.; Madland, D.G.; Myers, W.D.; Penttila, H.T.; Ragnarsson, I.; Reeder, P.L.; Robertson, G.H.; Rowley, N.; Schreiber, F.; Seifert, H.L.; Sherrill, B.M.; Siciliano, E.R.; Sprouse, G.D.; Stephens, F.S.; Subotic, K.; Talbert, W.; Toth, K.S.; Tu, X.L.; Vieira, D.J.; Villari, A.C.C.; Walters, W.B.; Wildenthal, B.H.; Wilhelmy, J.B.; Winger, J.A.; Wohn, F.K.; Wouters, J.M.; Zhou, X.G.; Zhou, Z.Y.

    1990-01-01

    This report outlines some of the nuclear structure topics discussed at the Los Alamos Workshop on the Science of Intense Radioactive Ion Beams (RIB). In it we also tried to convey some of the excitement of the participants for utilizing RIBs in their future research. The introduction of radioactive beams promises to be a major milestone for nuclear structure perhaps even more important than the last such advance in beams based on the advent of heavy-ion accelerators in the 1960's. RIBs not only will allow a vast number of new nuclei to be studies at the extremes of isospin, but the variety of combinations of exotic proton and neutron configurations should lead to entirely new phenomena. A number of these intriguing new studies and the profound consequences that they promise for understanding the structure of the atomic nucleus, nature's only many-body, strongly-inteacting quantum system, are discussed in the preceeding sections. However, as with any scientific frontier, the most interesting phenomena probably will be those that are not anticipated--they will be truly new

  8. Large structural modification with conserved conformation: analysis of delta(3)-fused aryl prolines in model beta-turns.

    Science.gov (United States)

    Jeannotte, Guillaume; Lubell, William D

    2004-11-10

    For the first time, the influence of a fused Delta3-arylproline on peptide conformation has been studied by the synthesis and comparison of the conformations of peptides containing proline and pyrrolo-proline, 3 (PyPro). Pyrrolo-proline was demonstrated to be a conservative replacement for Pro in model beta-turns, 4 and 5, as shown by their similar DMSO titration curves, cis/trans-isomer populations, and NOESY spectral data. Pyrrolo-proline may thus be used for studying the structure activity relationships of Pro-containing peptides with minimal modification of secondary structures.

  9. The Staphylococcus aureus extracellular adherence protein (Eap) adopts an elongated but structured conformation in solution.

    Science.gov (United States)

    Hammel, Michal; Nemecek, Daniel; Keightley, J Andrew; Thomas, George J; Geisbrecht, Brian V

    2007-12-01

    The extracellular adherence protein (Eap) of Staphylococcus aureus participates in a wide range of protein-protein interactions that facilitate the initiation and dissemination of Staphylococcal disease. In this report, we describe the use of a multidisciplinary approach to characterize the solution structure of full-length Eap. In contrast to previous reports suggesting that a six-domain isoform of Eap undergoes multimerization, sedimentation equilibrium analytical ultracentrifugation data revealed that a four-domain isoform of Eap is a monomer in solution. In vitro proteolysis and solution small angle X-ray scattering studies both indicate that Eap adopts an extended conformation in solution, where the linkers connecting sequential EAP modules are solvent exposed. Construction of a low-resolution model of full-length Eap using a combination of ab initio deconvolution of the SAXS data and rigid body modeling of the EAP domain crystal structure suggests that full-length Eap may present several unique concave surfaces capable of participating in ligand binding. These results also raise the possibility that such surfaces may be held together by additional interactions between adjacent EAP modules. This hypothesis is supported by a comparative Raman spectroscopic analysis of full-length Eap and a stoichiometric solution of the individual EAP modules, which indicates the presence of additional secondary structure and a greater extent of hydrogen/deuterium exchange protection in full-length Eap. Our results provide the first insight into the solution structure of full-length Eap and an experimental basis for interpreting the EAP domain crystal structures within the context of the full-length molecule. They also lay a foundation for future studies into the structural and molecular bases of Eap-mediated protein-protein interactions with its many ligands.

  10. Effects of Ecohydraulic Bank Stabilization Structures on Bank Stability and Macroinvertebrate Community in Surabaya River

    Directory of Open Access Journals (Sweden)

    Daru Setyo Rini

    2018-01-01

    Full Text Available There were 18 accelerated erosion sites identified along 7 km of Surabaya River Fishery Sanctuary Area. A model of ecohydraulic bank stabilization was applied to reduce bank erosion in Surabaya River at Gresik Regency Indonesia. The model is combination of reprofiled and revegetated bank with rock toe reinforcement and  addition of log groynes. Various native plant species were planted and naturally grown to establish multi-strata littoral vegetation structure. This study assessed effects of ecohydraulic bank stabilization on bank morphology, near bank velocity and littoral macroinvertebrate community during September 2014 to August 2016. The study found that rock toe enforcement, log groynes and reprofiled bank slope could stabilized the eroded bank, and littoral vegetation formation reduced near bank velocity at restored sites. There were 31 families of macroinvertebrate found in Surabaya River with high abundance of moderately pollution sensitive taxa Atyidae and pollution tolerant taxa Corixidae, Chironomidae and Tubificidae. The taxa richness, diversity index and abundance of sensitive and moderately sensitive macroinvertebrate group were increased after application of ecohydraulic bank stabilization at restored area. The results shown that ecohydraulic bank stabilization structure provides multi-benefits in improving bank stabilization against erosion and providing new micro-habitats for biotic community. Keywords:  ecohydraulic bank stabilization, macroinvertebrates, riparian restoration

  11. A reliable method for the stability analysis of structures ...

    African Journals Online (AJOL)

    The detection of structural configurations with singular tangent stiffness matrix is essential because they can be unstable. The secondary paths, especially in unstable buckling, can play the most important role in the loss of stability and collapse of the structure. A new method for reliable detection and accurate computation of ...

  12. Structure and stability of spiro-cyclic water clusters

    Indian Academy of Sciences (India)

    Administrator

    Abstract. The structure and stability of spiro-cyclic water clusters containing up to 32 water molecules have been ... due to its importance in various real life systems. 1–8. High level ... It is well-known from the crystal structure data- base that the ...

  13. Structure of Nuclei Far From Stability

    Energy Technology Data Exchange (ETDEWEB)

    Blackmon, Jeffery C. [Louisiana State Univ., Baton Rouge, LA (United States); Tribble, Robert E. [Texas A & M Univ., College Station, TX (United States); Sobotka, Lee G. [Washington Univ., St. Louis, MO (United States); Bertulani, Carlos [Texas A & M Univ., Commerce, TX (United States)

    2015-12-29

    The work performed under this grant has led to the development of a detection system that will be used to measure reaction rates for proton or neutron capture reactions at stellar energies on radioactive ions far from stability. The reaction rates are needed to better understand the physics of nucleosynthesis in explosive stellar processes such as supernovae and X-ray burst explosions. The radioactive ions will be produced at the Radioactive Ion Beam Facility (RIBF) at RIKEN near Tokyo, Japan. During the course of this work, the group involved in this project has expanded by several institutions in Europe and Japan and now involves collaborators from the U.S., Japan, Hungary, Romania, Germany, Spain, Italy, China, and South Korea. As part of the project, a novel design based on large-area silicon detectors has been built and tested and the performance characterized in a series of tests using particle beams with a variety of atomic numbers at the Cyclotron Institute of Texas A&M University and the Heavy Ion Medical Accelerator in Chiba facility (HIMAC) in Chiba, Japan. The work has involved mechanical construction of a special purpose vacuum chamber, with a precision mounting system for the silicon detectors, development of a new ASICs readout system that has applications with a wide variety of silicon detector systems, and the development of a data acquisition system that is integrated into the computer system being used at RIBF. The parts noted above that are needed to carry out the research program are completed and ready for installation. Several approved experiments that will use this system will be carried out in the near future. The experimental work has been delayed due to a large increase in the cost and availability of electrical power for RIBF that occurred following the massive earthquake and tsunami that hit Japan in the spring of 2011. Another component of the research carried out with this grant involved developing the theoretical tools that are

  14. Stability of Bulk Metallic Glass Structure. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Jain, H.; Williams, D. B.

    2003-06-01

    The fundamental origins of the stability of the (Pd-Ni){sub 80}P{sub 20} bulk metallic glasses (BMGs), a prototype for a whole class of BMG formers, were explored. While much of the properties of their BMGs have been characterized, their glass-stability have not been explained in terms of the atomic and electronic structure. The local structure around all three constituent atoms was obtained, in a complementary way, using extended X-ray absorption fine structure (EXAFS), to probe the nearest neighbor environment of the metals, and extended energy loss fine structure (EXELFS), to investigate the environment around P. The occupied electronic structure was investigated using X-ray photoelectron spectroscopy (XPS). The (Pd-Ni){sub 80}P{sub 20} BMGs receive their stability from cumulative, and interrelated, effects of both atomic and electronic origin. The stability of the (Pd-Ni){sub 80}P{sub 20} BMGs can be explained in terms of the stability of Pd{sub 60}Ni{sub 20}P{sub 20} and Pd{sub 30}Ni{sub 50}P{sub 20}, glasses at the end of BMG formation. The atomic structure in these alloys is very similar to those of the binary phosphide crystals near x=0 and x=80, which are trigonal prisms of Pd or Ni atoms surrounding P atoms. Such structures are known to exist in dense, randomly-packed systems. The structure of the best glass former in this series, Pd{sub 40}Ni{sub 40}P{sub 20} is further described by a weighted average of those of Pd{sub 30}Ni{sub 50}P{sub 20} and Pd{sub 60}Ni{sub 20}P{sub 20}. Bonding states present only in the ternary alloys were found and point to a further stabilization of the system through a negative heat of mixing between Pd and Ni atoms. The Nagel and Tauc criterion, correlating a decrease in the density of states at the Fermi level with an increase in the glass stability, was consistent with greater stability of the Pd{sub x}Ni{sub 80-x}P{sub 20} glasses with respect to the binary alloys of P. A valence electron concentration of 1.8 e/a, which

  15. The structure of nuclei far from stability

    International Nuclear Information System (INIS)

    Zganjar, E.F.

    1993-01-01

    Studies on nuclei near Z=82 contributed to the establishment of a new region of nuclear deformation and a new class of nuclear structure at closed shells. A important aspect of this work is the establishment of the connection between low-lying 0 + states in even endash even nuclei and the occurrence of shape coexistence in the odd-mass neighbors (E0 transitions in 185 Pt, shape coexistence in 184 Pt and 187 Au). A new type of picosecond lifetime measurement system capable of measuring the lifetime of states that decay only by internal conversion was developed and applied to the 186,188 Tl decay to determine the lifetime of the 0 2 + and 2 2 + deformed states in 186,188 Hg. A search for the population of superdeformed states in 192 Hg by the radioactive decay of 192 Tl was accomplished by using a prototype internal pair formation spectrometer

  16. Thin film structures and phase stability

    International Nuclear Information System (INIS)

    Clemens, B.M.; Johnson, W.L.

    1990-01-01

    This was a two day symposium, with invited and contributed papers as well as an evening poster session. The first day concentrated on solid state reactions with invited talks by Lindsay Greer from the University of Cambridge, King Tu from IBM Yorktown Heights, and Carl Thompson from MIT. Professor Greer observed that the diffusion of Zr is 10 6 times slower than that of Ni in amorphous NiZr, confirming that Ni is the mobile species in solid state amorphization. King Tu explained the formation of metastable phases in this film diffusion couples by the concept of maximum rate of free energy change. Carl Thompson discussed the formation of amorphous phases in metal silicon systems, and discussed a two stage nucleation and growth process. The contributed papers also generated discussion on topics such as phase segregation, amorphous silicide formation, room temperature oxidation of silicon, and nucleation during ion beam irradiation. There was a lively poster session on Monday evening with papers on a wide variety of topics covering the general area of thin film science. The second day had sessions Epitaxy and Multilayer Structure I and II, with the morning focussing on epitaxial and heteroepitaxial growth of thin films. Robin Farrow of IBM Almaden led off with an invited talk where he reported on some remarkable success he and his co-workers have had in growing single crystal epitaxial thin films and superlattices of silver, iron, cobalt and platinum on GaAs. This was followed by several talks on epitaxial growth and characterization. The afternoon focused on interfaces and structure of multilayered materials. A session on possible stress origins of the supermodulus effect was highlighted by lively interaction from the audience. Most of the papers presented at the symposium are presented in this book

  17. A new method for the characterization of strain-specific conformational stability of protease-sensitive and protease-resistant PrPSc.

    Directory of Open Access Journals (Sweden)

    Laura Pirisinu

    Full Text Available Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrP(Sc, a disease-associated isoform of the host-encoded cellular protein (PrP(C. Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrP(Sc. However, PrP(Sc is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrP(Sc aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrP(C and PrP(Sc by means of differential centrifugation. The conformational solubility and stability assay (CSSA was then developed by measuring PrP(Sc solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl](1/2 values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl](1/2 values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M, followed by sheep scrapie (2.2 M and by MM2 sCJD (1.6 M. In order to test the ability of CSSA to characterise protease-sensitive PrP(Sc, we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrP(Sc aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrP(Sc conformational stabilities of protease-resistant and protease-sensitive PrP(Sc and that it is a valuable tool

  18. Ab-initio conformational epitope structure prediction using genetic algorithm and SVM for vaccine design.

    Science.gov (United States)

    Moghram, Basem Ameen; Nabil, Emad; Badr, Amr

    2018-01-01

    T-cell epitope structure identification is a significant challenging immunoinformatic problem within epitope-based vaccine design. Epitopes or antigenic peptides are a set of amino acids that bind with the Major Histocompatibility Complex (MHC) molecules. The aim of this process is presented by Antigen Presenting Cells to be inspected by T-cells. MHC-molecule-binding epitopes are responsible for triggering the immune response to antigens. The epitope's three-dimensional (3D) molecular structure (i.e., tertiary structure) reflects its proper function. Therefore, the identification of MHC class-II epitopes structure is a significant step towards epitope-based vaccine design and understanding of the immune system. In this paper, we propose a new technique using a Genetic Algorithm for Predicting the Epitope Structure (GAPES), to predict the structure of MHC class-II epitopes based on their sequence. The proposed Elitist-based genetic algorithm for predicting the epitope's tertiary structure is based on Ab-Initio Empirical Conformational Energy Program for Peptides (ECEPP) Force Field Model. The developed secondary structure prediction technique relies on Ramachandran Plot. We used two alignment algorithms: the ROSS alignment and TM-Score alignment. We applied four different alignment approaches to calculate the similarity scores of the dataset under test. We utilized the support vector machine (SVM) classifier as an evaluation of the prediction performance. The prediction accuracy and the Area Under Receiver Operating Characteristic (ROC) Curve (AUC) were calculated as measures of performance. The calculations are performed on twelve similarity-reduced datasets of the Immune Epitope Data Base (IEDB) and a large dataset of peptide-binding affinities to HLA-DRB1*0101. The results showed that GAPES was reliable and very accurate. We achieved an average prediction accuracy of 93.50% and an average AUC of 0.974 in the IEDB dataset. Also, we achieved an accuracy of 95

  19. Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site.

    Directory of Open Access Journals (Sweden)

    Barna Dey

    2009-05-01

    Full Text Available The human immunodeficiency virus type 1 (HIV-1 exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region.

  20. Assessing the factor structure of the Chinese conformity to masculine norms inventory.

    Science.gov (United States)

    Rochelle, Tina L; Yim, K H

    2015-01-01

    The purpose of the present study was to examine the factor structure and assess the reliability of the Chinese Conformity to Masculine Norms Inventory-46 (CCMNI-46). Using a cohort of 254 Hong Kong-born Chinese males, scale reliability determination involved the internal consistencies of the entire instrument. Ages of respondents ranged from 18 to 81 years (M = 38.05; SD = 17.3). Confirmatory factor analysis provided support for the psychometric properties of the CCMNI-46, thus confirming the multidimensional structure of the CMNI-46 and the replicability of the CMNI using a Hong Kong Chinese sample. All items loaded onto the corresponding factor with the exception of one item from the emotional control subscale. The overall reliability of the CCMNI-46 was lower than previous Western studies and may well reflect the subtle diversity of masculinity across cultures. The findings offered psychometric support for use of the CCMNI-46 in research and practice regarding Hong Kong Chinese masculinity. The CCMNI-46 provides a useful template for the operationalization of masculine norms in Chinese society.

  1. Micropore Structure of Cement-Stabilized Gold Mine Tailings

    Directory of Open Access Journals (Sweden)

    Joon Kyu Lee

    2018-03-01

    Full Text Available Mine tailings have often to be stabilized by mixing them with cementing agents. In this study, the pore structure of gold tailings stabilized with Portland cement was evaluated by means of mercury intrusion porosimetry. The investigation was conducted on samples prepared with different fractions of tailings and cement as well as on samples activated with elevated temperature curing and chemical (CaCl2 addition. It was observed that all mixed samples exhibit a mono-modal pore size distribution, indicating that the cement-stabilized tailings are characterized by a single-porosity structure. The results also showed that the higher fraction of tailings and cement leads to a dense and finer pore structure. The total porosity of mixture samples decreases with increasing curing temperature and CaCl2 concentration due to the acceleration of hydration reaction.

  2. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility.

    Science.gov (United States)

    Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E; Schief, William R; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D

    2010-01-19

    The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate--and structurally plastic--layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated beta-sandwich and providing for conformational diversity used in immune evasion. A "layered" gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a beta-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.

  3. High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure

    NARCIS (Netherlands)

    M. Rosa-Garrido (Manuel); Chapski, D.J. (Douglas J.); Schmitt, A.D. (Anthony D.); Kimball, T.H. (Todd H.); Karbassi, E. (Elaheh); Monte, E. (Emma); Balderas, E. (Enrique); Pellegrini, M. (Matteo); Shih, T.-T. (Tsai-Ting); Soehalim, E. (Elizabeth); D.A. Liem (David); Ping, P. (Peipei); N.J. Galjart (Niels); Ren, S. (Shuxun); Wang, Y. (Yibin); Ren, B. (Bing); Vondriska, T.M. (Thomas M.)

    2017-01-01

    textabstractBACKGROUND: Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined.METHODS: To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation

  4. Protein energetic conformational analysis from NMR chemical shifts (PECAN) and its use in determining secondary structural elements

    Energy Technology Data Exchange (ETDEWEB)

    Eghbalnia, Hamid R.; Wang Liya; Bahrami, Arash [National Magnetic Resonance Facility at Madison, Biochemistry Department (United States); Assadi, Amir [University of Wisconsin-Madison, Mathematics Department (United States); Markley, John L. [National Magnetic Resonance Facility at Madison, Biochemistry Department (United States)], E-mail: eghbalni@nmrfam.wisc.edu

    2005-05-15

    We present an energy model that combines information from the amino acid sequence of a protein and available NMR chemical shifts for the purposes of identifying low energy conformations and determining elements of secondary structure. The model ('PECAN', Protein Energetic Conformational Analysis from NMR chemical shifts) optimizes a combination of sequence information and residue-specific statistical energy function to yield energetic descriptions most favorable to predicting secondary structure. Compared to prior methods for secondary structure determination, PECAN provides increased accuracy and range, particularly in regions of extended structure. Moreover, PECAN uses the energetics to identify residues located at the boundaries between regions of predicted secondary structure that may not fit the stringent secondary structure class definitions. The energy model offers insights into the local energetic patterns that underlie conformational preferences. For example, it shows that the information content for defining secondary structure is localized about a residue and reaches a maximum when two residues on either side are considered. The current release of the PECAN software determines the well-defined regions of secondary structure in novel proteins with assigned chemical shifts with an overall accuracy of 90%, which is close to the practical limit of achievable accuracy in classifying the states.

  5. Protein energetic conformational analysis from NMR chemical shifts (PECAN) and its use in determining secondary structural elements

    International Nuclear Information System (INIS)

    Eghbalnia, Hamid R.; Wang Liya; Bahrami, Arash; Assadi, Amir; Markley, John L.

    2005-01-01

    We present an energy model that combines information from the amino acid sequence of a protein and available NMR chemical shifts for the purposes of identifying low energy conformations and determining elements of secondary structure. The model ('PECAN', Protein Energetic Conformational Analysis from NMR chemical shifts) optimizes a combination of sequence information and residue-specific statistical energy function to yield energetic descriptions most favorable to predicting secondary structure. Compared to prior methods for secondary structure determination, PECAN provides increased accuracy and range, particularly in regions of extended structure. Moreover, PECAN uses the energetics to identify residues located at the boundaries between regions of predicted secondary structure that may not fit the stringent secondary structure class definitions. The energy model offers insights into the local energetic patterns that underlie conformational preferences. For example, it shows that the information content for defining secondary structure is localized about a residue and reaches a maximum when two residues on either side are considered. The current release of the PECAN software determines the well-defined regions of secondary structure in novel proteins with assigned chemical shifts with an overall accuracy of 90%, which is close to the practical limit of achievable accuracy in classifying the states

  6. Selection of conformational states in self-assembled surface structures formed from an oligo(naphthylene-ethynylene) 3-bit binary switch

    DEFF Research Database (Denmark)

    Ning, Yanxiao; Cramer, Jacob Roland; Nuermaimaiti, Ajiguli

    2015-01-01

    ). The conformations result from binary positions of n = 3 naphtalene units on a linear oligo(naphthylene-ethynylene) backbone. On Au(111), inter-molecular interactions involving carboxyl and bulky tert-butyl-phenyl functional groups induce the molecules to form two ordered phases with brick-wall and lamella structure...... conformational states. Together these observations imply selection and adaptation of conformational states upon molecular self-assembly. From DFT modeling and statistical analysis of the molecular conformations, the observed selection of conformational states is attributed to steric interaction between...

  7. Structure-activity relationships of pyrethroid insecticides. Part 2. The use of molecular dynamics for conformation searching and average parameter calculation

    Science.gov (United States)

    Hudson, Brian D.; George, Ashley R.; Ford, Martyn G.; Livingstone, David J.

    1992-04-01

    Molecular dynamics simulations have been performed on a number of conformationally flexible pyrethroid insecticides. The results indicate that molecular dynamics is a suitable tool for conformational searching of small molecules given suitable simulation parameters. The structures derived from the simulations are compared with the static conformation used in a previous study. Various physicochemical parameters have been calculated for a set of conformations selected from the simulations using multivariate analysis. The averaged values of the parameters over the selected set (and the factors derived from them) are compared with the single conformation values used in the previous study.

  8. Electrochemical stability of ionic clathrate hydrates and their structural consideration

    International Nuclear Information System (INIS)

    Lee, Wonhee; Lim, Dongwook; Lee, Huen

    2013-01-01

    Although electrochemical stability is an essential factor in relation to the potential applications of ionic clathrate hydrates to solid electrolytes, most studies regarding the proton conductors have focused on their ionic conductivity and thermal stability. Solid electrolytes in various electrochemical devices have to endure the applied potentials; thus, we examined the linear sweep voltammograms of various tetraalkylammonium hydroxide hydrates in order to shed light on the trend of electrochemical stability depending on the hydrate structure. We revealed that the electrochemical stability of Me 4 NOH hydrates is mainly affected by both their ionic concentration and cage occupancy. In particular, the true clathrate structures of β-Me 4 NOH hydrates are more electrochemically stable than their α-forms that possess partially broken hydrogen bonds. We also observed that the binary THF–Pr 4 NOH and pure Bu 4 NOH clathrate hydrates exhibit greater electrochemical stability than those of pure Me 4 NOH hydrates having lower or similar ionic concentrations. These results are considered to arise from the fact that each of the Pr 4 N + and Bu 4 N + ions occupies an extended space comprising four cages, which leads to stabilization of the larger unit, whereas a Me 4 N + ion is completely included only in one cage

  9. Conformation Generation: The State of the Art.

    Science.gov (United States)

    Hawkins, Paul C D

    2017-08-28

    The generation of conformations for small molecules is a problem of continuing interest in cheminformatics and computational drug discovery. This review will present an overview of methods used to sample conformational space, focusing on those methods designed for organic molecules commonly of interest in drug discovery. Different approaches to both the sampling of conformational space and the scoring of conformational stability will be compared and contrasted, with an emphasis on those methods suitable for conformer sampling of large numbers of drug-like molecules. Particular attention will be devoted to the appropriate utilization of information from experimental solid-state structures in validating and evaluating the performance of these tools. The review will conclude with some areas worthy of further investigation.

  10. Structural stability and electronic structure of YCu ductile ...

    African Journals Online (AJOL)

    We investigate the structural, elastic and electronic properties of cubic YCu intermetallic compound. Which crystallize in the CsCl- B2 type structure, the investigated using the first principle full potential linearized augmented plane wave method (FP-LAPW) within density functional Theory (DFT). We used generalized ...

  11. Determination of the populations and structures of multiple conformers in an ensemble from NMR data: Multiple-copy refinement of nucleic acid structures using floating weights

    International Nuclear Information System (INIS)

    Goerler, Adrian; Ulyanov, Nikolai B.; James, Thomas L.

    2000-01-01

    A new algorithm is presented for determination of structural conformers and their populations based on NMR data. Restrained Metropolis Monte Carlo simulations or restrained energy minimizations are performed for several copies of a molecule simultaneously. The calculations are restrained with dipolar relaxation rates derived from measured NOE intensities via complete relaxation matrix analysis. The novel feature of the algorithm is that the weights of individual conformers are determined in every refinement step, by the quadratic programming algorithm, in such a way that the restraint energy is minimized. Its design ensures that the calculated populations of the individual conformers are based only on experimental restraints. Presence of internally inconsistent restraints is the driving force for determination of distinct multiple conformers. The method is applied to various simulated test systems. Conformational calculations on nucleic acids are carried out using generalized helical parameters with the program DNAminiCarlo. From different mixtures of A- and B-DNA, minor fractions as low as 10% could be determined with restrained energy minimization. For B-DNA with three local conformers (C2'-endo, O4'-exo, C3'-endo), the minor O4'-exo conformer could not be reliably determined using NOE data typically measured for DNA. The other two conformers, C2'-endo and C3'-endo, could be reproduced by Metropolis Monte Carlo simulated annealing. The behavior of the algorithm in various situations is analyzed, and a number of refinement protocols are discussed. Prior to application of this algorithm to each experimental system, it is suggested that the presence of internal inconsistencies in experimental data be ascertained. In addition, because the performance of the algorithm depends on the type of conformers involved and experimental data available, it is advisable to carry out test calculations with simulated data modeling each experimental system studied

  12. Towards a "Golden Standard" for computing globin stability: Stability and structure sensitivity of myoglobin mutants

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2015-01-01

    Fast and accurate computation of protein stability is increasingly important for e.g. protein engineering and protein misfolding diseases, but no consensus methods exist for important proteins such as globins, and performance may depend on the type of structural input given. This paper reports be...

  13. The crystal structure and stability of molybdenum at ultrahigh pressures

    International Nuclear Information System (INIS)

    Jona, F; Marcus, P M

    2005-01-01

    Crystal structures and their stabilities for molybdenum under increasing hydrostatic pressures are investigated by first-principles calculations of the Gibbs free energy. Three structures are considered: body-centred cubic (bcc, the ground state at zero pressure), hexagonal close-packed (hcp) and face-centred cubic (fcc). For each structure and each pressure (up to 8 Mbar) the equilibrium states are found from minima of the Gibbs free energy at zero temperature. The stability is tested by calculating the elastic constants and checking whether they satisfy the appropriate stability conditions. The bcc structure is confirmed to be stable at zero pressure and at 6 Mbar. At and above 6.2 M-bar the ground-state structure changes to hcp, which is found to be stable at 7 M-bar. At 7.7 Mbar another transition occurs, and the ground-state structure changes from hcp to fcc. The fcc structure, which is unstable at zero pressure, becomes metastable over the range from 3 to 7.7 M-bar and becomes the ground state at higher pressures (at least up to 8 Mbar). Direct confirmation of these calculated transition pressures with experiment is not now possible, as the maximum static pressure currently reached experimentally is 5.6 Mbar, where Mo is found to be still in the bcc phase

  14. Differentiable dynamical systems an introduction to structural stability and hyperbolicity

    CERN Document Server

    Wen, Lan

    2016-01-01

    This is a graduate text in differentiable dynamical systems. It focuses on structural stability and hyperbolicity, a topic that is central to the field. Starting with the basic concepts of dynamical systems, analyzing the historic systems of the Smale horseshoe, Anosov toral automorphisms, and the solenoid attractor, the book develops the hyperbolic theory first for hyperbolic fixed points and then for general hyperbolic sets. The problems of stable manifolds, structural stability, and shadowing property are investigated, which lead to a highlight of the book, the \\Omega-stability theorem of Smale. While the content is rather standard, a key objective of the book is to present a thorough treatment for some tough material that has remained an obstacle to teaching and learning the subject matter. The treatment is straightforward and hence could be particularly suitable for self-study. Selected solutions are available electronically for instructors only. Please send email to textbooks@ams.org for more informatio...

  15. Calcium Stabilized And Geogrid Reinforced Soil Structures In Seismic Areas

    International Nuclear Information System (INIS)

    Rimoldi, Pietro; Intra, Edoardo

    2008-01-01

    In many areas of Italy, and particularly in high seismic areas, there is no or very little availability of granular soils: hence embankments and retaining structures are often built using the locally available fine soil. For improving the geotechnical characteristics of such soils and/or for building steep faced structures, there are three possible techniques: calcium stabilization, geogrid reinforcement, and the combination of both ones, that is calcium stabilized and reinforced soil. The present paper aims to evaluate these three techniques in terms of performance, design and construction, by carrying out FEM modeling and stability analyses of the same reference embankments, made up of soil improved with each one of the three techniques, both in static and dynamic conditions. Finally two case histories are illustrated, showing the practical application of the above outlined techniques

  16. Ab initio study on structural stability of uranium carbide

    International Nuclear Information System (INIS)

    Sahoo, B.D.; Joshi, K.D.; Gupta, Satish C.

    2013-01-01

    First principles calculations have been performed using plane wave pseudopotential and full potential linearized augmented plane wave (FP-LAPW) methods to analyze structural, elastic and dynamic stability of UC under hydrostatic compression. Our calculations within pseudopotential method suggest that the rocksalt (B1) structure will transform to body centered orthorhombic (bco) structure at ∼21.5 GPa. The FP-LAPW calculations put this transition at 23 GPa. The transition pressures determined from our calculations though agree reasonably with the experimental value of 27 GPa, the high pressure bco structure suggested by theory differs slightly from the experimentally reported pseudo bco phase. The elastic stability analysis of B1 phase suggests that the B1 to bco transition is driven by the failure of C 44 modulus. This finding is further substantiated by the lattice dynamic calculations which demonstrate that the B1 phase becomes dynamically unstable around the transition pressure and the instability is of long wavelength nature

  17. Molecular Basis of Inactive B-RAF(WT) and B-RAF(V600E) Ligand Inhibition, Selectivity and Conformational Stability: An in Silico Study

    DEFF Research Database (Denmark)

    Fratev, Filip Filipov; Jonsdottir, Svava Osk; Mihaylova, E.

    2009-01-01

    -PBSA and local-binding energy (LBE) approaches. The conformational stability of the unbounded kinases and in particular the processes of the B-RAF(V600E) mutant activation were analyzed. A unique salt bridge network formed mainly by the catalytic residues was identified in the unbounded B...... effects on B-RAF(V600E) was revealed, which can explain the low mutant selectivity observed for numerous inhibitors. Our results suggest that the interactions between the activation segment and the alpha C-helix, as well as between the residues in the salt bridge network, are the major mechanism of the B...

  18. Structural Stability and Hydraulic Conductivity Of Nkpologu Sandy ...

    African Journals Online (AJOL)

    Studies were conducted in the runoff plots at the University of Nigeria Nsukka Teaching and Resesarch Farm in 2010 and 2011 to monitor the changes in structural stability and saturated hydraulic conductivity (Ksat) of Nkpologu sandy loam soil under different cover management practices. The management practices were ...

  19. The structure of nuclei far from beta stability

    International Nuclear Information System (INIS)

    Zganjar, E.F.

    1992-01-01

    This report discusses: shape coexistence and intruder states; the electric monopole transition in nuclei; gold isotopes; platinum isotopes; iridium isotopes; search for superdeformation in 192 Hg; search for population of superformed states in 194 Pb using 194 Bi β + -decay; detailed nuclear structure studies far from stability; prototype internal pair spectrometer; and picosecond lifetime spectrometer

  20. The stability of gabion walls for earth retaining structures

    OpenAIRE

    Mahyuddin Ramli; T.J.r. Karasu; Eethar Thanon Dawood

    2013-01-01

    The stability of earth retaining structures in flood prone areas has become a serious problem in many countries. The two most basic causes of failure arising from flooding are scouring and erosion of the foundation of the superstructure. Hence, a number of structures like bridges employ scour-arresting devices, e.g., gabions to acting on the piers and abutments during flooding. Research was therefore undertaken to improve gabion resistance against lateral movement by means of an interlocking ...

  1. A conformationally locked tricyclic nucleoside. Synthesis, crystal structure and incorporation into oligonucleotides

    DEFF Research Database (Denmark)

    Ravn, Jacob; Thorup, Niels; Nielsen, Poul

    2001-01-01

    A tricyclic nucleoside is synthesised from a bicyclic nucleoside precursor by applying a stereoselective dihydroxylation, a regioselective tosylation and an intramolecular ether formation. This tricyclic nucleoside is constructed as a conformationally locked thymidine analogue and has been analys...

  2. Conformational flexibility of BECN1: Essential to its key role in autophagy and beyond: BECN1 Structure and Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Mei, Yang [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050; Glover, Karen [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050; Su, Minfei [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050; Sinha, Sangita C. [Department of Chemistry and Biochemistry, North Dakota State University, Fargo North Dakota 58108-6050

    2016-08-13

    BECN1 (Beclin 1), a highly conserved eukaryotic protein, is a key regulator of autophagy, a cellular homeostasis pathway, and also participates in vacuolar protein sorting, endocytic trafficking, and apoptosis. BECN1 is important for embryonic development, the innate immune response, tumor suppression, and protection against neurodegenerative disorders, diabetes, and heart disease. BECN1 mediates autophagy as a core component of the class III phosphatidylinositol 3-kinase complexes. However, the exact mechanism by which it regulates the activity of these complexes, or mediates its other diverse functions is unclear. BECN1 interacts with several diverse protein partners, perhaps serving as a scaffold or interaction hub for autophagy. Based on extensive structural, biophysical and bioinformatics analyses, BECN1 consists of an intrinsically disordered region (IDR), which includes a BH3 homology domain (BH3D); a flexible helical domain (FHD); a coiled-coil domain (CCD); and a β-α-repeated autophagy-specific domain (BARAD). Each of these BECN1 domains mediates multiple diverse interactions that involve concomitant conformational changes. Thus, BECN1 conformational flexibility likely plays a key role in facilitating diverse protein interactions. Further, BECN1 conformation and interactions are also modulated by numerous post-translational modifications. A better structure-based understanding of the interplay between different BECN1 conformational and binding states, and the impact of post-translational modifications will be essential to elucidating the mechanism of its multiple biological roles.

  3. Structural basis of lipid-driven conformational transitions in the KvAP voltage-sensing domain.

    Science.gov (United States)

    Li, Qufei; Wanderling, Sherry; Sompornpisut, Pornthep; Perozo, Eduardo

    2014-02-01

    Voltage-gated ion channels respond to transmembrane electric fields through reorientations of the positively charged S4 helix within the voltage-sensing domain (VSD). Despite a wealth of structural and functional data, the details of this conformational change remain controversial. Recent electrophysiological evidence showed that equilibrium between the resting ('down') and activated ('up') conformations of the KvAP VSD from Aeropyrum pernix can be biased through reconstitution in lipids with or without phosphate groups. We investigated the structural transition between these functional states, using site-directed spin-labeling and EPR spectroscopic methods. Solvent accessibility and interhelical distance determinations suggest that KvAP gates through S4 movements involving an ∼3-Å upward tilt and simultaneous ∼2-Å axial shift. This motion leads to large accessibly changes in the intracellular water-filled crevice and supports a new model of gating that combines structural rearrangements and electric-field remodeling.

  4. Early structure of LPG partially premixed conically stabilized flames

    KAUST Repository

    Elbaz, Ayman M.

    2013-01-01

    This paper presents experimental investigation of LPG partially premixed turbulent flames stabilized within a conical nozzle burner under constant degree of partial premixing. The stability limits and mean flame structure are presented based on the mean gas temperature and the concentration of CO, O 2, NO, and HC at the flame early region of reaction. The investigation covered the influence of the nozzle cone angle, the jet exit velocity and the jet equivalence ratio. The stability results show that the flames with cone are more stable than those without cone. For conical stabilized flames, the stability results exhibit three different sensitivity regions between the jet velocity and equivalence ratio. The inflame measurements prove that the flame stability could be attributed to the triple flame structure at the flame leading edge. The data show that the triple flame structure is influenced by cone angle, the jet velocity and the equivalence ratio. The flame is believed to be controlled by the recirculation flow inside the cone. Increasing the cone angle induced higher air entrainment to the reaction zone as depicted by a higher O 2 concentration within the flame leading edge. Increasing the jet velocity to a certain limit enhances the intensity of combustion at the flame leading edge, while excessive increase in jet velocity reduces this intensity. At a fixed jet velocity the higher the equivalence ratio, the higher the amount of fuel diffused and engulfed to the reaction zone, the more delay of the combustion completion and the higher the emission concentrations of the flame. © 2012 Elsevier Inc.

  5. Kinetic stability and membrane structure of liposomes during in vitro infant intestinal digestion: Effect of cholesterol and lactoferrin.

    Science.gov (United States)

    Liu, Weilin; Wei, Fuqiang; Ye, Aiqian; Tian, Mengmeng; Han, Jianzhong

    2017-09-01

    The effects of cholesterol and lactoferrin on the kinetic stability and membrane structural integrity of negatively charged liposomes under in vitro infant intestinal digestion conditions were elucidated using dynamic light scattering, pH-stat titration, Fourier transform infrared spectroscopy, and pyrene steady state fluorescence probes. The liposomes had a smaller particle diameter, a wider size distribution, and a greater negative charge after digestion. The incorporation of cholesterol into the phospholipid bilayers resulted in a more ordered conformation in the aliphatic tail region and reduced micropolarity, indicating that cholesterol can improve the structural stability of liposomal membranes against intestinal environmental stress. Lactoferrin coverage facilitated the release of free fatty acids and increased the microfluidity of the bilayers, reducing the structural integrity of the liposomes. This study provides useful information on the design of liposomes and other microcapsules with improved and controlled release properties during digestion for particular groups of people. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Protein secondary structure and stability determined by combining exoproteolysis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Villanueva, Josep; Villegas, Virtudes; Querol, Enrique; Avilés, Francesc X; Serrano, Luis

    2002-09-01

    In the post-genomic era, several projects focused on the massive experimental resolution of the three-dimensional structures of all the proteins of different organisms have been initiated. Simultaneously, significant progress has been made in the ab initio prediction of protein three-dimensional structure. One of the keys to the success of such a prediction is the use of local information (i.e. secondary structure). Here we describe a new limited proteolysis methodology, based on the use of unspecific exoproteases coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), to map quickly secondary structure elements of a protein from both ends, the N- and C-termini. We show that the proteolytic patterns (mass spectra series) obtained can be interpreted in the light of the conformation and local stability of the analyzed proteins, a direct correlation being observed between the predicted and the experimentally derived protein secondary structure. Further, this methodology can be easily applied to check rapidly the folding state of a protein and characterize mutational effects on protein conformation and stability. Moreover, given global stability information, this methodology allows one to locate the protein regions of increased or decreased conformational stability. All of this can be done with a small fraction of the amount of protein required by most of the other methods for conformational analysis. Thus limited exoproteolysis, together with MALDI-TOF MS, can be a useful tool to achieve quickly the elucidation of protein structure and stability. Copyright 2002 John Wiley & Sons, Ltd.

  7. Strength Analysis of Coconut Fiber Stabilized Earth for Farm Structures

    Science.gov (United States)

    Enokela, O. S.; P. O, Alada

    2012-07-01

    Investigation of the strength characteristic of soil from alluvial deposit of River Benue in makurdi stabilized with coconut fiber as a stabilizer was carried as local building material for farm structure. Processed coconut fibers were mixed with the soil at four different mix ratios of 1% fiber, 2% fiber, 3% fiber and 4% fiber by percentage weight with 0% fiber as control. Compaction test and compressive strength were carried out on the various stabilizing ratio. From the compaction test, the correlation between the maximum dry density and optimum moisture content is a second order polynomial with a coefficient of 63% obtained at1.91kg/m3and 20.0% respectively while the compressive strength test shows an optimum failure load of 8.62N/mm2 at 2%fibre:100% soil mix ratio at 2.16 maximum dry density.

  8. Effects of lysine residues on structural characteristics and stability of tau proteins

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myeongsang; Baek, Inchul; Choi, Hyunsung; Kim, Jae In; Na, Sungsoo, E-mail: nass@korea.ac.kr

    2015-10-23

    Pathological amyloid proteins have been implicated in neuro-degenerative diseases, specifically Alzheimer's, Parkinson's, Lewy-body diseases and prion related diseases. In prion related diseases, functional tau proteins can be transformed into pathological agents by environmental factors, including oxidative stress, inflammation, Aβ-mediated toxicity and covalent modification. These pathological agents are stable under physiological conditions and are not easily degraded. This un-degradable characteristic of tau proteins enables their utilization as functional materials to capturing the carbon dioxides. For the proper utilization of amyloid proteins as functional materials efficiently, a basic study regarding their structural characteristic is necessary. Here, we investigated the basic tau protein structure of wild-type (WT) and tau proteins with lysine residues mutation at glutamic residue (Q2K) on tau protein at atomistic scale. We also reported the size effect of both the WT and Q2K structures, which allowed us to identify the stability of those amyloid structures. - Highlights: • Lysine mutation effect alters the structure conformation and characteristic of tau. • Over the 15 layers both WT and Q2K models, both tau proteins undergo fractions. • Lysine mutation causes the increment of non-bonded energy and solvent accessible surface area. • Structural instability of Q2K model was proved by the number of hydrogen bonds analysis.

  9. Effects of lysine residues on structural characteristics and stability of tau proteins

    International Nuclear Information System (INIS)

    Lee, Myeongsang; Baek, Inchul; Choi, Hyunsung; Kim, Jae In; Na, Sungsoo

    2015-01-01

    Pathological amyloid proteins have been implicated in neuro-degenerative diseases, specifically Alzheimer's, Parkinson's, Lewy-body diseases and prion related diseases. In prion related diseases, functional tau proteins can be transformed into pathological agents by environmental factors, including oxidative stress, inflammation, Aβ-mediated toxicity and covalent modification. These pathological agents are stable under physiological conditions and are not easily degraded. This un-degradable characteristic of tau proteins enables their utilization as functional materials to capturing the carbon dioxides. For the proper utilization of amyloid proteins as functional materials efficiently, a basic study regarding their structural characteristic is necessary. Here, we investigated the basic tau protein structure of wild-type (WT) and tau proteins with lysine residues mutation at glutamic residue (Q2K) on tau protein at atomistic scale. We also reported the size effect of both the WT and Q2K structures, which allowed us to identify the stability of those amyloid structures. - Highlights: • Lysine mutation effect alters the structure conformation and characteristic of tau. • Over the 15 layers both WT and Q2K models, both tau proteins undergo fractions. • Lysine mutation causes the increment of non-bonded energy and solvent accessible surface area. • Structural instability of Q2K model was proved by the number of hydrogen bonds analysis.

  10. Atomistic structural ensemble refinement reveals non-native structure stabilizes a sub-millisecond folding intermediate of CheY

    International Nuclear Information System (INIS)

    Shi, Jade; Schwantes, Christian; Bilsel, Osman

    2017-01-01

    The dynamics of globular proteins can be described in terms of transitions between a folded native state and less-populated intermediates, or excited states, which can play critical roles in both protein folding and function. Excited states are by definition transient species, and therefore are difficult to characterize using current experimental techniques. We report an atomistic model of the excited state ensemble of a stabilized mutant of an extensively studied flavodoxin fold protein CheY. We employed a hybrid simulation and experimental approach in which an aggregate 42 milliseconds of all-atom molecular dynamics were used as an informative prior for the structure of the excited state ensemble. The resulting prior was then refined against small-angle X-ray scattering (SAXS) data employing an established method (EROS). The most striking feature of the resulting excited state ensemble was an unstructured N-terminus stabilized by non-native contacts in a conformation that is topologically simpler than the native state. We then predict incisive single molecule FRET experiments, using these results, as a means of model validation. Our study demonstrates the paradigm of uniting simulation and experiment in a statistical model to study the structure of protein excited states and rationally design validating experiments.

  11. Fundamental insights into conformational stability and orbital interactions of antioxidant (+)-catechin species and complexation of (+)-catechin with zinc(II) and oxovanadium(IV)

    Science.gov (United States)

    Yasarawan, Nuttawisit; Thipyapong, Khajadpai; Sirichai, Somsak; Ruangpornvisuti, Vithaya

    2013-09-01

    Conformational stability of (+)-catechin species in water has been examined with density functional theory, associated with the polarizable continuum model (PCM) of solvation. Factors such as electron delocalization, lone-pair electron donation and intramolecular hydrogen bonding substantially contribute to the conformational stabilization. Upon deprotonation, the HOMO and LUMO energies for (+)-catechin are both elevated; the energy gaps for the deprotonated species are narrower than the energy gap for the neutral species. The preferential deprotonation occurs at the C3'-, C5-, C7- and C4'-OH groups successively. The pKa value at 9.3 predicted for the most acidic OH group agrees well with previous experimental data; however the values are overestimated for the less acidic OH groups due to limitations of the PCM for charged solutes and/or complex nature of true deprotonation pathways. Formation of hydrogen radicals should be promoted at high pH values following the bond dissociation enthalpies. Complexation of (+)-catechin with either zinc(II) or oxovanadium(IV) is favored at the 1:1 metal-to-ligand (M:L) mole ratio, with the oxovanadium(IV) complex showing higher reaction preference. At M:L = 1:2, formation of two isomeric complexes are plausible for each type of metal ion. Effects of stoichiometry and isomerism on the computational spectral features of the possibly formed metal complexes have been described.

  12. Broadband Chirped-Pulse Fourier-Transform Microwave Spectroscopic Investigation of the Structures of Three Diethylsilane Conformers

    Science.gov (United States)

    Steber, Amanda L.; Obenchain, Daniel A.; Peebles, Rebecca A.; Peebles, Sean A.; Neill, Justin L.; Muckle, Matt T.; Pate, Brooks H.; Guirgis, Gamil A.

    2009-06-01

    The rotational spectrum of diethylsilane has been assigned using broadband chirped-pulse Fourier-transform microwave (CP-FTMW) spectroscopy. Previously, Fourier-transform microwave rotational spectra were observed using a Balle-Flygare type instrument for the ^{28}Si isotopologues of the gauche-gauche, trans-gauche, and trans-trans conformers. In the present study, a broadband microwave spectrum was obtained at the University of Virginia, taking advantage of the ability to perform deep signal averaging to increase the measurement sensitivity. To obtain a full structural determination of the conformers of this molecule, spectra for the ^{29}Si, ^{30}Si, and single ^{13}C substitutions for the gauche-gauche, the trans-gauche, and the trans-trans species were assigned. Substitution (r_s) structures and inertial fit (r_0) structures were determined and a comparison between the experimental and ab initio structures will be presented. For the ^{28}Si isotopologues, the percent differences between the experimental and ab initio rotational constants are less than 1.5% for the trans-trans and trans-gauche and are between 2.0 and 5.0% for the gauche-gauche conformer. The structural parameters will be compared between this molecule, diethylgermane and other silicon containing molecules and the relative abundances of the three conformers will be discussed. S.A. Peebles, M.M. Serafin, R.A. Peebles, G.A. Guirgis, and H.D. Stidham J. Phys. Chem. A, (2009), DOI: 10.1021/jp811049n.

  13. Myotonic Dystrophy Type 1 RNA Crystal Structures Reveal Heterogeneous 1 × 1 Nucleotide UU Internal Loop Conformations

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Amit; Park, HaJeung; Fang, Pengfei; Parkesh, Raman; Guo, Min; Nettles, Kendall W.; Disney, Matthew D. (Scripps)

    2012-03-27

    RNA internal loops often display a variety of conformations in solution. Herein, we visualize conformational heterogeneity in the context of the 5'CUG/3'GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1). Specifically, two crystal structures of a model DM1 triplet repeating construct, 5'r[{und UU}GGGC(C{und U}G){sub 3}GUCC]{sub 2}, refined to 2.20 and 1.52 {angstrom} resolution are disclosed. Here, differences in the orientation of the 5' dangling UU end between the two structures induce changes in the backbone groove width, which reveals that noncanonical 1 x 1 nucleotide UU internal loops can display an ensemble of pairing conformations. In the 2.20 {angstrom} structure, CUGa, the 5' UU forms a one hydrogen-bonded pair with a 5' UU of a neighboring helix in the unit cell to form a pseudoinfinite helix. The central 1 x 1 nucleotide UU internal loop has no hydrogen bonds, while the terminal 1 x 1 nucleotide UU internal loops each form a one-hydrogen bond pair. In the 1.52 {angstrom} structure, CUGb, the 5' UU dangling end is tucked into the major groove of the duplex. While the canonically paired bases show no change in base pairing, in CUGb the terminal 1 x 1 nucleotide UU internal loops now form two hydrogen-bonded pairs. Thus, the shift in the major groove induced by the 5' UU dangling end alters noncanonical base patterns. Collectively, these structures indicate that 1 x 1 nucleotide UU internal loops in DM1 may sample multiple conformations in vivo. This observation has implications for the recognition of this RNA, and other repeating transcripts, by protein and small molecule ligands.

  14. A Novel Method Using Abstract Convex Underestimation in Ab-Initio Protein Structure Prediction for Guiding Search in Conformational Feature Space.

    Science.gov (United States)

    Hao, Xiao-Hu; Zhang, Gui-Jun; Zhou, Xiao-Gen; Yu, Xu-Feng

    2016-01-01

    To address the searching problem of protein conformational space in ab-initio protein structure prediction, a novel method using abstract convex underestimation (ACUE) based on the framework of evolutionary algorithm was proposed. Computing such conformations, essential to associate structural and functional information with gene sequences, is challenging due to the high-dimensionality and rugged energy surface of the protein conformational space. As a consequence, the dimension of protein conformational space should be reduced to a proper level. In this paper, the high-dimensionality original conformational space was converted into feature space whose dimension is considerably reduced by feature extraction technique. And, the underestimate space could be constructed according to abstract convex theory. Thus, the entropy effect caused by searching in the high-dimensionality conformational space could be avoided through such conversion. The tight lower bound estimate information was obtained to guide the searching direction, and the invalid searching area in which the global optimal solution is not located could be eliminated in advance. Moreover, instead of expensively calculating the energy of conformations in the original conformational space, the estimate value is employed to judge if the conformation is worth exploring to reduce the evaluation time, thereby making computational cost lower and the searching process more efficient. Additionally, fragment assembly and the Monte Carlo method are combined to generate a series of metastable conformations by sampling in the conformational space. The proposed method provides a novel technique to solve the searching problem of protein conformational space. Twenty small-to-medium structurally diverse proteins were tested, and the proposed ACUE method was compared with It Fix, HEA, Rosetta and the developed method LEDE without underestimate information. Test results show that the ACUE method can more rapidly and more

  15. Structural characteristics and harmonic vibrational analysis of the stable conformer of 2,3-epoxypropanol by quantum chemical methods.

    Science.gov (United States)

    Arjunan, V; Rani, T; Santhanam, R; Mohan, S

    2012-10-01

    The FT-IR and FT-Raman spectra of H bond inner conformer of 2,3-epoxypropanol have been recorded in the regions 3700-400 and 3700-100 cm(-1), respectively. The spectra were interpreted in terms of fundamentals modes, combination and overtone bands. The normal coordinate analysis was carried out to confirm the precision of the assignments. The structure of the conformers H bond inner and H bond outer1 were optimised and the structural characteristics were determined by density functional theory (DFT) using B3LYP and MP2 methods with 6-31G** and 6-311++G** basis sets. The vibrational frequencies were calculated in all these methods and were compared with the experimental frequencies which yield good agreement between observed and calculated frequencies. The electronic properties HOMO and LUMO energies were measured by time-dependent TD-DFT approach. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. A finite integration method for conformal, structured-grid, electromagnetic simulation

    International Nuclear Information System (INIS)

    Cooke, S.J.; Shtokhamer, R.; Mondelli, A.A.; Levush, B.

    2006-01-01

    We describe a numerical scheme for solving Maxwell's equations in the frequency domain on a conformal, structured, non-orthogonal, multi-block mesh. By considering Maxwell's equations in a volume parameterized by dimensionless curvilinear coordinates, we obtain a set of tensor equations that are a continuum analogue of common circuit equations, and that separate the metrical and metric-free parts of Maxwell's equations and the material constitutive relations. We discretize these equations using a new formulation that treats the electric field and magnetic induction using simple basis-function representations to obtain a discrete form of Faraday's law of induction, but that uses finite integral representations for the displacement current and magnetic field to obtain a discrete form of Ampere's law, as in the finite integration technique [T. Weiland, A discretization method for the solution of Maxwell's equations for six-component fields, Electron. Commun. (AE U) 31 (1977) 116; T. Weiland, Time domain electromagnetic field computation with finite difference methods, Int. J. Numer. Model: Electron. Netw. Dev. Field 9 (1996) 295-319]. We thereby derive new projection operators for the discrete tensor material equations and obtain a compact numerical scheme for the discrete differential operators. This scheme is shown to exhibit significantly reduced numerical dispersion when compared to the standard linear finite element method. We take advantage of the mesh structure on a block-by-block basis to implement these numerical operators efficiently, and achieve computational speed with modest memory requirements when compared to explicit sparse matrix storage. Using the Jacobi-Davidson [G.L.G. Sleijpen, H.A. van der Vorst, A Jacobi-Davidson iteration method for linear eigenvalue problems, SIAM J. Matrix Anal. Appl. 17 (2) (1996) 401-425; S.J. Cooke, B. Levush, Eigenmode solution of 2-D and 3-D electromagnetic cavities containing absorbing materials using the Jacobi

  17. The structure and conformations of piracetam (2-oxo-1-pyrrolidineacetamide): Gas-phase electron diffraction and quantum chemical calculations

    Science.gov (United States)

    Ksenafontov, Denis N.; Moiseeva, Natalia F.; Khristenko, Lyudmila V.; Karasev, Nikolai M.; Shishkov, Igor F.; Vilkov, Lev V.

    2010-12-01

    The geometric structure of piracetam was studied by quantum chemical calculations (DFT and ab initio), gas electron diffraction (GED), and FTIR spectroscopy. Two stable mirror symmetric isomers of piracetam were found. The conformation of pyrrolidine ring is an envelope in which the C4 atom deviates from the ring plane, the angle between the planes (C3 sbnd C4 sbnd C5) and (C2 sbnd C3 sbnd C5) is 154.1°. The direction of the deviation is the same as that of the side acetamide group. The piracetam molecule is stabilized in the gas phase by an intramolecular hydrogen bond between the N9H 2 group and the oxygen O6, bonded to C2. The principal structural parameters ( re, Å and ∠e, degrees; uncertainties are 3 σLS values) were found to be: r(С3 sbnd С4) = 1.533(1), r(C4 sbnd C5) = 1.540(1), r(N1 sbnd C5) = 1.456(1), r(C2 sbnd C3) = 1.520(1), r(N1 sbnd C7) = 1.452(1), r(C7 sbnd C8) = 1.537(1), r(N1 sbnd C2) = 1.365(2), r(C8 sbnd N9) = 1.360(2), r(C2 dbnd O6) = 1.229(1), r(C8 dbnd O10) = 1.221(1), ∠C2 sbnd N1 sbnd C5 = 113.4(6), ∠N1 sbnd C2 sbnd C3 = 106.9(6), ∠N1 sbnd C7 sbnd C8 = 111.9(6), ∠C7 sbnd C8 sbnd N9 = 112.5(6), ∠N1 sbnd C2 sbnd O6 = 123.0(4), ∠C3 sbnd N1 sbnd C7 = 120.4(4), ∠C7 sbnd C8 sbnd O10 = 120.2(4), ∠C5 sbnd N1 sbnd C2 sbnd O6 = 170(6), ∠C3 sbnd C2 sbnd N1 sbnd C7 = 178(6), ∠C2 sbnd N1 sbnd C7 sbnd C8 = 84.2, ∠N1 sbnd C7 sbnd C8 sbnd O10 = 111.9.

  18. Towards a "Golden Standard" for computing globin stability: Stability and structure sensitivity of myoglobin mutants.

    Science.gov (United States)

    Kepp, Kasper P

    2015-10-01

    Fast and accurate computation of protein stability is increasingly important for e.g. protein engineering and protein misfolding diseases, but no consensus methods exist for important proteins such as globins, and performance may depend on the type of structural input given. This paper reports benchmarking of six protein stability calculators (POPMUSIC 2.1, I-Mutant 2.0, I-Mutant 3.0, CUPSAT, SDM, and mCSM) against 134 experimental stability changes for mutations of sperm-whale myoglobin. Six different high-resolution structures were used to test structure sensitivity that may impair protein calculations. The trend accuracy of the methods decreased as I-Mutant 2.0 (R=0.64-0.65), SDM (R=0.57-0.60), POPMUSIC2.1 (R=0.54-0.57), I-Mutant 3.0 (R=0.53-0.55), mCSM (R=0.35-0.47), and CUPSAT (R=0.25-0.48). The mean signed errors increased as SDMMean absolute errors increased as I-Mutant 2.0Structural sensitivity increased as I-Mutant 3.0 (0.05)structures and reveal structure-dependent effects even in the near-atomic resolution limit. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Importance of structural stability to success of mourning dove nests

    Science.gov (United States)

    Coon, R.A.; Nichols, J.D.; Percival, H.F.

    1981-01-01

    Studies of nest-site selection and nesting habitats often involve a "characterization" of nests and of habitats in which nests are found. Our objective in the present work is to identify nest-site characteristics that are associated with variation in components of Mourning Dove (Zenaida macroura) fitness (e.g. the probability of a nest succeeding), as opposed to simply "characterizing" dove nest sites. If certain nest- site characteristics affect the probability that a nest will succeed, then we suspect that these characteristics will be associated with either concealment (the probability of detection by certain predators) or structural stability (the probability of eggs or entire nests falling to the ground as a result of wind, rain storms, parental activity, etc.). Although other workers agree that structural stability is an important determinant of Mourning Dove nesting success (e.g. McClure 1944: 384; Woolfenden and Rohwer 1969: 59), we are aware of no actual tests of this hypothesis.

  20. Formation, structure, and stability of MHD intermediate shocks

    International Nuclear Information System (INIS)

    Wu, C.C.

    1990-01-01

    Contrary to the usual belief that MHD intermediate shocks are extraneous, the author has recently shown by numerical solutions of dissipative MHD equations that intermediate shocks are admissible and can be formed through nonlinear wave steepening from continuous waves. In this paper, the formation, structure and stability of intermediate shocks in dissipative MHD are considered in detail. The differences between the conventional theory and his are pointed out and clarified. He shows that all four types of intermediate shocks can be formed from smooth waves. He also shows that there are free parameters in the structure of the intermediate shocks, and that these parameters are related to the shock stability. In addition, he shows that a rotational discontinuity can not exist with finite width, indicate how this is related to the existence of time-dependent intermediate shocks, and show why the conventional theory is not a good approximation to dissipative MHD solutions whenever there is rotation in magnetic field

  1. Structural stability of interaction networks against negative external fields

    Science.gov (United States)

    Yoon, S.; Goltsev, A. V.; Mendes, J. F. F.

    2018-04-01

    We explore structural stability of weighted and unweighted networks of positively interacting agents against a negative external field. We study how the agents support the activity of each other to confront the negative field, which suppresses the activity of agents and can lead to collapse of the whole network. The competition between the interactions and the field shape the structure of stable states of the system. In unweighted networks (uniform interactions) the stable states have the structure of k -cores of the interaction network. The interplay between the topology and the distribution of weights (heterogeneous interactions) impacts strongly the structural stability against a negative field, especially in the case of fat-tailed distributions of weights. We show that apart from critical slowing down there is also a critical change in the system structure that precedes the network collapse. The change can serve as an early warning of the critical transition. To characterize changes of network structure we develop a method based on statistical analysis of the k -core organization and so-called "corona" clusters belonging to the k -cores.

  2. Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

    Energy Technology Data Exchange (ETDEWEB)

    Fyfe, Cameron D.; Grinter, Rhys; Josts, Inokentijs; Mosbahi, Khedidja [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Roszak, Aleksander W. [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Cogdell, Richard J.; Wall, Daniel M.; Burchmore, Richard J. S.; Byron, Olwyn; Walker, Daniel, E-mail: daniel.walker@glasgow.ac.uk [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom)

    2015-06-30

    The X-ray structure of protease-cleaved E. coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. Bacterial α-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli α-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli α-2-macroglobulin and human α-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group.

  3. Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

    International Nuclear Information System (INIS)

    Fyfe, Cameron D.; Grinter, Rhys; Josts, Inokentijs; Mosbahi, Khedidja; Roszak, Aleksander W.; Cogdell, Richard J.; Wall, Daniel M.; Burchmore, Richard J. S.; Byron, Olwyn; Walker, Daniel

    2015-01-01

    The X-ray structure of protease-cleaved E. coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. Bacterial α-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli α-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli α-2-macroglobulin and human α-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group

  4. PWL approximation of nonlinear dynamical systems, part I: structural stability

    International Nuclear Information System (INIS)

    Storace, M; De Feo, O

    2005-01-01

    This paper and its companion address the problem of the approximation/identification of nonlinear dynamical systems depending on parameters, with a view to their circuit implementation. The proposed method is based on a piecewise-linear approximation technique. In particular, this paper describes the approximation method and applies it to some particularly significant dynamical systems (topological normal forms). The structural stability of the PWL approximations of such systems is investigated through a bifurcation analysis (via continuation methods)

  5. The structure of nuclei far from beta stability

    International Nuclear Information System (INIS)

    Zganjar, E.F.

    1991-01-01

    This report discusses the structural of nuclei for from beta stability of the following isotopes: thallium isotopes; mercury isotopes; gold isotopes; platinum isotopes; iridium isotopes; the neutron deficient rare-earth, Z = 57-72 region, and the neutron deficient Z = 50-56 region; also discussed are in-beam spectroscopy in the A = 70 region and shape coexistence, intruder states, and EO transitions

  6. Ab initio calculations of the structure and conformations of 2,6-lutidine

    International Nuclear Information System (INIS)

    Porcinai, S.; Foggi, P.

    1997-01-01

    Ab initio molecular orbital calculations at the SCF level have been utilized to determine the structure and the electronic and vibrational properties of 2,6-lutidine (2,6-dimethyl-pyridine) in the ground electronic state. Comparative calculations have been performed on the parent molecule pyridine. Structure predictions of both molecules are in good agreement with experimental data. The most stable rotamer of 2,6-lutidine has C 2v symmetry with one of the C-H bonds of both the methyl groups lying in the plane of the aromatic ring and pointing in the opposite direction with respect to the nitrogen atom. This is the result of the minimization of competing forces deriving from steric hindrance and electronic stabilization. Vibrational frequencies and oscillator strengths of C-H stretching in the fundamental region have been calculated for both pyridine and the most stable rotamer of 2,6-lutidine and compared to IR data obtained in pure liquids. The potential energy profile of the C-H bond in and out of plane has been investigated up to five times the equilibrium distance. The trend of the potential curves confirms that the C-H bond lying in the plane has a higher dissociation energy than that of the in-plane bonds as observed in experiments on vibrational overtones

  7. Prospects in the use of aptamers for characterizing the structure and stability of bioactive proteins and peptides in food.

    Science.gov (United States)

    Agyei, Dominic; Acquah, Caleb; Tan, Kei Xian; Hii, Hieng Kok; Rajendran, Subin R C K; Udenigwe, Chibuike C; Danquah, Michael K

    2018-01-01

    Food-derived bioactive proteins and peptides have gained acceptance among researchers, food manufacturers and consumers as health-enhancing functional food components that also serve as natural alternatives for disease prevention and/or management. Bioactivity in food proteins and peptides is determined by their conformations and binding characteristics, which in turn depend on their primary and secondary structures. To maintain their bioactivities, the molecular integrity of bioactive peptides must remain intact, and this warrants the study of peptide form and structure, ideally with robust, highly specific and sensitive techniques. Short single-stranded nucleic acids (i.e. aptamers) are known to have high affinity for cognate targets such as proteins and peptides. Aptamers can be produced cost-effectively and chemically derivatized to increase their stability and shelf life. Their improved binding characteristics and minimal modification of the target molecular signature suggests their suitability for real-time detection of conformational changes in both proteins and peptides. This review discusses the developmental progress of systematic evolution of ligands by exponential enrichment (SELEX), an iterative technology for generating cost-effective aptamers with low dissociation constants (K d ) for monitoring the form and structure of bioactive proteins and peptides. The review also presents case studies of this technique in monitoring the structural stability of bioactive peptide formulations to encourage applications in functional foods. The challenges and potential of aptamers in this research field are also discussed. Graphical abstract Advancing bioactive proteins and peptide functionality via aptameric ligands.

  8. Partially O-Alkylated Thiacalix[4]arenes: Synthesis, Molecular and Crystal Structures, Conformational Behaviour

    Czech Academy of Sciences Publication Activity Database

    Dvořáková, H.; Lang, J.; Vlach, J.; Sýkora, Jan; Čajan, M.; Himl, M.; Pojarová, M.; Stibor, I.; Lhoták, P.

    2007-01-01

    Roč. 72, č. 19 (2007), s. 7157-7166 ISSN 0022-3263 Institutional research plan: CEZ:AV0Z40720504 Keywords : thiacalixarene * conformation conversion * x-ray crystallography Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.959, year: 2007

  9. Structures and Stability of Metal Amidoboranes (MAB): Density Functional Calculations

    International Nuclear Information System (INIS)

    Li Cailin; Wu Chaoling; Chen Yungui; Zhou Jingjing; Zheng Xin; Pang Lijuan; Deng Gang

    2010-01-01

    Molecule geometry structures, frequencies, and energetic stabilities of ammonia borane (AB, NH 3 BH 3 ) and metal amidoboranes (MAB, MNH 2 BH 3 ), formed by substituting H atom in AB with one of main group metal atoms, have been investigated by density-functional theory and optimized at the B3LYP levels with 6-311G++ (3df, 3pd) basic set. Their structural parameters and infrared spectrum characteristic peaks have been predicted, which should be the criterion of a successfully synthesized material. Several parameters such as binding energies, vibrational frequencies, and the energy gaps between the HOMO and the LUMO have been adopted to characterize and evaluate their structure stabilities. It is also found that the binding energies and HOMO-LUMO energy gaps of the MAB obviously change with the substitution of the atoms. MgAB has the lowest binding energy and is easier to decompose than any other substitutional structures under same conditions, while CaAB has the highest chemical activity. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  10. Impact of branched structures on cycloalkane ignition in a motored engine: Detailed product and conformational analyses

    KAUST Repository

    Kang, Dongil

    2015-04-01

    The ignition process of ethylcyclohexane (ECH) and its two isomers, 1,3-dimethylcyclohexane (13DMCH) and 1,2-dimethylcyclohexane (12DMCH) was investigated in a modified CFR engine. The experiment was conducted with intake air temperature of 155. °C, equivalence ratio of 0.5 and engine speed of 600. rpm. The engine compression ratio (CR) was gradually increased in a stepwise manner until autoignition occurred. It was found that ECH exhibited a significantly higher oxidation reactivity compared to its two isomers. The autoignition criterion was based on CO emissions and the apparent heat release rates. Ethylcyclohexane (ECH) indicated noticeable two stage ignition behavior, while less significant heat release occurred for the two isomers at comparable conditions. The mole fractions of unreacted fuel and stable intermediate species over a wide range of compression ratios were analyzed by GC-MS and GC-FID. Most of the species indicated constant rates of formation and the trends of relative yield to unreacted fuel are well in agreement with the oxidation reactivity in the low temperature regime. The major intermediate species are revealed as a group of conjugate olefins, which possess the same molecular structure as the original fuel compound except for the presence of a double carbon bond. Conjugate olefins were mostly formed through (1,4) H-shift isomerization during the low temperature oxidation of alkylcyclohexanes. Conformation analysis explains the reactivity differences in the three isomers as well as the fractions of intermediate species. The hydrogen availability located in alkyl substituents plays an important role in determining oxidation reactivity, requiring less activation energy for abstraction through the (1,5) H-shift isomerization. This reactivity difference contributes to building up the major intermediate species observed during oxidation of each test fuel. 12DMCH, whose ignition reactivity is the lowest, less favors β-scission of C-C backbone of

  11. Structural stability, electronic structure and mechanical properties of actinide carbides AnC (An = U, Np)

    International Nuclear Information System (INIS)

    Manikandan, M.; Santhosh, M.; Rajeswarapalanichamy, R.

    2016-01-01

    Ab initio calculations are performed to investigate the structural stability, electronic structure and mechanical properties of actinide carbides AnC (An=U, Np) for three different crystal structures, namely NaCl, CsCl and ZnS. Among the considered structures, NaCl structure is found to be the most stable structure for these carbides at normal pressure. A pressure induced structural phase transition from NaCl to ZnS is observed. The electronic structure reveals that these carbides are metals. The calculated elastic constants indicate that these carbides are mechanically stable at normal pressure.

  12. Quantum chemical studies on molecular structural conformations and hydrated forms of salicylamide and O-hydroxybenzoyl cyanide

    Science.gov (United States)

    Anandan, K.; Kolandaivel, P.; Kumaresan, R.

    Ab initio and density functional theory (DFT) methods have been employed to study the molecular structural conformations and hydrated forms of both salicylamide (SAM) and O-hydroxybenzoyl cyanide (OHBC). Molecular geometries and energetics have been obtained in the gaseous phase by employing the Møller-Plesset type 2 MP2/6-311G(2d,2p) and B3LYP/6-311G(2d,2p) levels of theory. The presence of an electron-releasing group (SAM) leads to an increase in the energy of the molecular system, while the presence of an electron-withdrawing group (OHBC) drastically decreases the energy. Chemical reactivity parameters (η and μ) have been calculated using the energy values of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) obtained at the Hartree-Fock (HF)/6-311G(2d,2p) level of theory for all the conformers and the principle of maximum hardness (MHP) has been tested. The condensed Fukui functions have been calculated using the atomic charges obtained through the natural bond orbital (NBO) analysis scheme for all the optimized structures at the B3LYP/6-311G(2d,2p) level of theory, and the most reactive sites of the molecules have been identified. Nuclear magnetic resonance (NMR) studies have been carried out at the B3LYP/6-311G(2d,2p) level of theory for all the conformers in the gaseous phase on the basis of the method of Cheeseman and coworkers. The calculated chemical shift values have been used to discuss the delocalization activity of the electron clouds. The dimeric structures of the most stable conformers of both SAM and OHBC in the gaseous phase have been optimized at the B3LYP/6-311G(2d,2p) level of theory, and the interaction energies have been calculated. The most stable conformers of both compounds bear an intramolecular hydrogen bond, which gives rise to the formation of a pseudo-aromatic ring. These conformers have been allowed to interact with the water molecule. Special emphasis has been given to analysis of the

  13. The stability of gabion walls for earth retaining structures

    Directory of Open Access Journals (Sweden)

    Mahyuddin Ramli

    2013-12-01

    Full Text Available The stability of earth retaining structures in flood prone areas has become a serious problem in many countries. The two most basic causes of failure arising from flooding are scouring and erosion of the foundation of the superstructure. Hence, a number of structures like bridges employ scour-arresting devices, e.g., gabions to acting on the piers and abutments during flooding. Research was therefore undertaken to improve gabion resistance against lateral movement by means of an interlocking configuration instead of the conventional stack-and-pair system. This involved simulating lateral thrusts against two dimensionally identical retaining wall systems configured according to the rectangular and hexagonal gabion type. The evolution of deformation observed suggested that the interlocking design exhibits better structural integrity than the conventional box gabion-based wall in resisting lateral movement and therefore warrants consideration for use as an appropriate scour-arresting device for earth retaining structures.

  14. Elastic stability of biaxially loaded longitudinally stiffened composite structures.

    Science.gov (United States)

    Viswanathan, A. V.; Tamekuni, M.; Tripp, L. L.

    1973-01-01

    A linear analysis method is presented for the elastic stability of structures of uniform cross section, that may be idealized as an assemblage of laminated plate-strips, flat and curved, and beams. Each plate-strip and beam covers the entire length of the structure and is simply supported on the edges normal to the longitudinal axis. Arbitrary boundary conditions may be specified on any external longitudinal side of plate-strips. The structure or selected plate-strips may be loaded in any desired combination of inplane biaxial loads. The analysis simultaneously considers all modes of instability and is applicable for the buckling of laminated composite structures. Some numerical results are presented to indicate possible applications.

  15. Contribution of simple saccharides to the stabilization of amyloid structure

    International Nuclear Information System (INIS)

    Fung, Justin; Darabie, Audrey A.; McLaurin, JoAnne

    2005-01-01

    The use of osmolytes or chaperones to stabilize proteins/peptides that misfold in neurodegenerative diseases is an attractive concept for drug development. We have investigated the role of a series of small carbohydrates for protection of the natively structured Alzheimer's amyloid-β peptides (Aβ). Using circular dichroism spectroscopy to follow the β-structural transitions and electron microscopy to examine tertiary structural characteristics, we demonstrate that the hydrogen bonding capacity of the carbohydrate determines the inhibition or promotion of fibrillogenesis. Three sugar molecules that vary only in their distribution of potential H-bonding partners promote various structural changes in Aβ. Two of these sugar molecules are excluded from Aβ during aggregation and promote mature fibre growth, while the other binds Aβ promoting nucleation and the accumulation of protofibrils. Our studies suggest that utilization of a combinatorial strategy to alter H-bonding capacity across a simple carbohydrate molecule may represent a novel drug design strategy

  16. Synthesis and conformational properties of oligonucleotides incorporating 2'-O-phosphorylated ribonucleotides as structural motifs of pre-tRNA splicing intermediates.

    Science.gov (United States)

    Tsuruoka, H; Shohda, K; Wada, T; Sekine, M

    2000-11-03

    To synthesize oligonucleotides containing 2'-O-phosphate groups, four kinds of ribonucleoside 3'-phosphoramidite building blocks 6a-d having the bis(2-cyano-1,1-dimethylethoxy)thiophosphoryl (BCMETP) group were prepared according to our previous phosphorylation procedure. These phosphoramidite units 6a-d were not contaminated with 3'-regioisomers and were successfully applied to solid-phase synthesis to give oligodeoxyuridylates 15, 16 and oligouridylates 21, 22. Self-complementary Drew-Dickerson DNA 12mers 24-28 replaced by a 2'-O-phosphorylated ribonucleotide at various positions were similarly synthesized. In these syntheses, it turned out that KI(3) was the most effective reagent for oxidative desulfurization of the initially generated thiophosphate group to the phosphate group on polymer supports. Without using this conversion step, a tridecadeoxyuridylate 17 incorporating a 2'-O-thiophosphorylated uridine derivative was also synthesized. To investigate the effect of the 2'-phosphate group on the thermal stability and 3D-structure of DNA(RNA) duplexes, T(m) measurement of the self-complementary oligonucleotides obtained and MD simulation of heptamer duplexes 33-36 were carried out. According to these analyses, it was suggested that the nucleoside ribose moiety phosphorylated at the 2'-hydroxyl function predominantly preferred C2'-endo to C3'-endo conformation in DNA duplexes so that it did not significantly affect the stability of the DNA duplex. On the other hand, the 2'-modified ribose moiety was expelled to give a C3'-endo conformation in RNA duplexes so that the RNA duplexes were extremely destabilized.

  17. 1H and 31P resonance assignments and secondary structure of hairpin conformer of IA mismatched oligonucleotide d-GGTACIAGTACC

    International Nuclear Information System (INIS)

    Chary, K.V.R.; Rastogi, V.K.; Govil, Girjesh

    1994-01-01

    Almost complete 1 H and 31 P resonance assignments of two coexisting conformers, duplex and an hairpin, of d-GGTACIAGTACC at 1.25mM concentration and 305 K have been achieved. The results demonstrate that the hairpin conformer has a structure with two purines I6 and A7 forming a two-base loop on a B-DNA stem. Stacking is continued on the 5'-side of the loop, with the I6 stacked upon C5. The base A7, on the 3'-side of the loop stacks partially with I6. The glycosidic angle for G8 is in the anti domain and it maintains normal Watson-Crick base-pairing with the opposite C5. (author). 28 refs., 7 figs., 2 tabs

  18. Structure of Dynamic, Taxol-Stabilized, and GMPPCP-Stabilized Microtubule.

    Science.gov (United States)

    Ginsburg, Avi; Shemesh, Asaf; Millgram, Abigail; Dharan, Raviv; Levi-Kalisman, Yael; Ringel, Israel; Raviv, Uri

    2017-09-14

    Microtubule (MT) is made of αβ-tubulin heterodimers that dynamically assemble into a hollow nanotube composed of straight protofilaments. MT dynamics is facilitated by hydrolysis of guanosine-5'-triphosphate (GTP) and can be inhibited by either anticancer agents like taxol or the nonhydrolyzable GTP analogues like GMPPCP. Using high-resolution synchrotron X-ray scattering, we have measured and analyzed the scattering curves from solutions of dynamic MT (in other words, in the presence of excess GTP and free of dynamic-inhibiting agents) and examined the effect of two MT stabilizers: taxol and GMPPCP. Previously, we have analyzed the structure of dynamic MT by docking the atomic model of tubulin dimer onto a 3-start left handed helical lattice, derived from the PDB ID 3J6F . 3J6F corresponds to a MT with 14 protofilaments. In this paper, we took into account the possibility of having MT structures containing between 12 and 15 protofilaments. MTs with 12 protofilaments were never observed. We determined the radii, the pitch, and the distribution of protofilament number that best fit the scattering data from dynamic MT or stabilized MT by taxol or GMPPCP. We found that the protofilament number distribution shifted when the MT was stabilized. Taxol increased the mass fraction of MT with 13 protofilaments and decreased the mass fraction of MT with 14 protofilaments. GMPPCP reduced the mass fraction of MT with 15 protofilaments and increased the mass fraction of MT with 14 protofilaments. The pitch, however, remained unchanged regardless of whether the MT was dynamic or stabilized. Higher tubulin concentrations increased the fraction of dynamic MT with 14 protofilaments.

  19. Application of a high-throughput relative chemical stability assay to screen therapeutic protein formulations by assessment of conformational stability and correlation to aggregation propensity.

    Science.gov (United States)

    Rizzo, Joseph M; Shi, Shuai; Li, Yunsong; Semple, Andrew; Esposito, Jessica J; Yu, Shenjiang; Richardson, Daisy; Antochshuk, Valentyn; Shameem, Mohammed

    2015-05-01

    In this study, an automated high-throughput relative chemical stability (RCS) assay was developed in which various therapeutic proteins were assessed to determine stability based on the resistance to denaturation post introduction to a chaotrope titration. Detection mechanisms of both intrinsic fluorescence and near UV circular dichroism (near-UV CD) are demonstrated. Assay robustness was investigated by comparing multiple independent assays and achieving r(2) values >0.95 for curve overlays. The complete reversibility of the assay was demonstrated by intrinsic fluorescence, near-UV CD, and biologic potency. To highlight the method utility, we compared the RCS assay with differential scanning calorimetry and dynamic scanning fluorimetry methodologies. Utilizing C1/2 values obtained from the RCS assay, formulation rank-ordering of 12 different mAb formulations was performed. The prediction of long-term stability on protein aggregation is obtained by demonstrating a good correlation with an r(2) of 0.83 between RCS and empirical aggregation propensity data. RCS promises to be an extremely useful tool to aid in candidate formulation development efforts based on the complete reversibility of the method to allow for multiple assessments without protein loss and the strong correlation between the C1/2 data obtained and accelerated stability under stressed conditions. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Role of quaternary structure in muscle creatine kinase stability: tryptophan 210 is important for dimer cohesion.

    Science.gov (United States)

    Perraut, C; Clottes, E; Leydier, C; Vial, C; Marcillat, O

    1998-07-01

    A mutant of the dimeric rabbit muscle creatine kinase (MM-CK) in which tryptophan 210 was replaced has been studied to assess the role of this residue in dimer cohesion and the importance of the dimeric state for the native enzyme stability. Wild-type protein equilibrium unfolding induced by guanidine hydrochloride occurs through intermediate states with formation of a molten globule and a premolten globule. Unlike the wild-type enzyme, the mutant inactivates at lower denaturant concentration and the loss of enzymatic activity is accompanied by the dissociation of the dimer into two apparently compact monomers. However, the Stokes radius of the monomer increases with denaturant concentration as determined by size exclusion chromatography, indicating that, upon monomerization, the protein structure is destabilized. Binding of 8-anilinonaphthalene-1-sulfonate shows that the dissociated monomer exposes hydrophobic patches at its surface, suggesting that it could be a molten globule. At higher denaturant concentrations, both wild-type and mutant follow similar denaturation pathways with formation of a premolten globule around 1.5-M guanidine, indicating that tryptophan 210 does not contribute to a large extent to the monomer conformational stability, which may be ensured in the dimeric state through quaternary interactions.

  1. Structure and stability of charged colloid-nanoparticle mixtures

    Science.gov (United States)

    Weight, Braden M.; Denton, Alan R.

    2018-03-01

    Physical properties of colloidal materials can be modified by addition of nanoparticles. Within a model of like-charged mixtures of particles governed by effective electrostatic interactions, we explore the influence of charged nanoparticles on the structure and thermodynamic phase stability of charge-stabilized colloidal suspensions. Focusing on salt-free mixtures of particles of high size and charge asymmetry, interacting via repulsive Yukawa effective pair potentials, we perform molecular dynamics simulations and compute radial distribution functions and static structure factors. Analysis of these structural properties indicates that increasing the charge and concentration of nanoparticles progressively weakens correlations between charged colloids. We show that addition of charged nanoparticles to a suspension of like-charged colloids can induce a colloidal crystal to melt and can facilitate aggregation of a fluid suspension due to attractive van der Waals interactions. We attribute the destabilizing influence of charged nanoparticles to enhanced screening of electrostatic interactions, which weakens repulsion between charged colloids. This interpretation is consistent with recent predictions of an effective interaction theory of charged colloid-nanoparticle mixtures.

  2. Adenine Nucleotide Analogues Locked in a Northern Methanocarba Conformation: Enhanced Stability and Potency as P2Y1 Receptor Agonists

    Science.gov (United States)

    Ravi, R. Gnana; Kim, Hak Sung; Servos, Jörg; Zimmermann, Herbert; Lee, Kyeong; Maddileti, Savitri; Boyer, José L.; Harden, T. Kendall; Jacobson, Kenneth A.

    2016-01-01

    Preference for the Northern (N) ring conformation of the ribose moiety of nucleotide 5′-triphosphate agonists at P2Y1, P2Y2, P2Y4, and P2Y11 receptors, but not P2Y6 receptors, was established using a ring-constrained methanocarba (a 3.1.0-bicyclohexane) ring as a ribose substitute (Kim et al. J. Med. Chem. 2002, 45, 208–218.). We have now combined the ring-constrained (N)-methanocarba modification of adenine nucleotides with other functionalities known to enhance potency at P2 receptors. The potency of the newly synthesized analogues was determined in the stimulation of phospholipase C through activation of turkey erythrocyte P2Y1 or human P2Y1 and P2Y2 receptors stably expressed in astrocytoma cells. An (N)-methanocarba-2-methylthio-ADP analogue displayed an EC50 at the hP2Y1 receptor of 0.40 nM and was 55-fold more potent than the corresponding triphosphate and 16-fold more potent than the riboside 5′-diphosphate. 2-Cl–(N)-methanocarba-ATP and its N6-Me analogue were also highly selective, full agonists at P2Y1 receptors. The (N)-methanocarba-2-methylthio and 2-chloromonophosphate analogues were full agonists exhibiting micromolar potency at P2Y1 receptors, while the corresponding ribosides were inactive. Although β,γ-methylene-ATP was inactive at P2Y receptors, β,γ-methylene-(N)-methanocarba-ATP was a potent hP2Y1 receptor agonist with an EC50 of 160 nM and was selective versus hP2Y2 and hP2Y4 receptors. The rates of hydrolysis of Northern (N) and Southern (S) methanocarba analogues of AMP by rat 5′-ectonucleotidase were negligible. The rates of hydrolysis of the corresponding triphosphates by recombinant rat NTPDase1 and 2 were studied. Both isomers were hydrolyzed by NTPDase 1 at about half the rate of ATP hydrolysis. The (N) isomer was hardly hydrolyzed by NTPDase 2, while the (S) isomer was hydrolyzed at one-third of the rate of ATP hydrolysis. This suggests that new, more stable and selective nucleotide agonists may be designed on the basis of

  3. Effect of polyethylene glycol conjugation on conformational and colloidal stability of a monoclonal antibody antigen-binding fragment (Fab').

    Science.gov (United States)

    Roque, Cristopher; Sheung, Anthony; Rahman, Nausheen; Ausar, S Fernando

    2015-02-02

    We have investigated the effects of site specific "hinge" polyethylene glycol conjugation (PEGylation) on thermal, pH, and colloidal stability of a monoclonal antibody antigen-binding fragment (Fab') using a variety of biophysical techniques. The results obtained by circular dichroism (CD), ultraviolet (UV) absorbance, and fluorescence spectroscopy suggested that the physical stability of the Fab' is maximized at pH 6-7 with no apparent differences due to PEGylation. Temperature-induced aggregation experiments revealed that PEGylation was able to increase the transition temperature, as well as prevent the formation of visible and subvisible aggregates. Statistical comparison of the three-index empirical phase diagram (EPD) revealed significant differences in thermal and pH stability signatures between Fab' and PEG-Fab'. Upon mechanical stress, micro-flow imaging (MFI) and measurement of the optical density at 360 nm showed that the PEG-Fab' had significantly higher resistance to surface-induced aggregation compared to the Fab'. Analysis of the interaction parameter, kD, indicated repulsive intermolecular forces for PEG-Fab' and attractive forces for Fab'. In conclusion, PEGylation appears to protect Fab' against thermal and mechanical stress-induced aggregation, likely due to a steric hindrance mechanism.

  4. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-08-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  5. A Method to Predict the Structure and Stability of RNA/RNA Complexes.

    Science.gov (United States)

    Xu, Xiaojun; Chen, Shi-Jie

    2016-01-01

    RNA/RNA interactions are essential for genomic RNA dimerization and regulation of gene expression. Intermolecular loop-loop base pairing is a widespread and functionally important tertiary structure motif in RNA machinery. However, computational prediction of intermolecular loop-loop base pairing is challenged by the entropy and free energy calculation due to the conformational constraint and the intermolecular interactions. In this chapter, we describe a recently developed statistical mechanics-based method for the prediction of RNA/RNA complex structures and stabilities. The method is based on the virtual bond RNA folding model (Vfold). The main emphasis in the method is placed on the evaluation of the entropy and free energy for the loops, especially tertiary kissing loops. The method also uses recursive partition function calculations and two-step screening algorithm for large, complicated structures of RNA/RNA complexes. As case studies, we use the HIV-1 Mal dimer and the siRNA/HIV-1 mutant (T4) to illustrate the method.

  6. Conformational control of cofactors in nature: The effect of methoxy group orientation on the electronic structure of ubisemiquinone

    Science.gov (United States)

    De Almeida, Wagner B.; O'Malley, Patrick J.

    2018-03-01

    Ubiquinone is the key electron and proton transfer agent in biology. Its mechanism involves the formation of its intermediate one-electron reduced form, the ubisemiquinone radical. This is formed in a protein-bound form which permits the semiquinone to vary its electronic and redox properties. This can be achieved by hydrogen bonding acceptance by one or both oxygen atoms or as we now propose by restricted orientations for the methoxy groups of the headgroup. We show how the orientation of the two methoxy groups of the quinone headgroup affects the electronic structure of the semiquinone form and demonstrate a large dependence of the ubisemiquinone spin density distribution on the orientation each methoxy group takes with respect to the headgroup ring plane. This is shown to significantly modify associated hyperfine couplings which in turn needs to be accounted for in interpreting experimental values in vivo. The study uncovers the key potential role the methoxy group orientation can play in controlling the electronic structure and spin density of ubisemiquinone and provides an electronic-level insight into the variation in electron affinity and redox potential of ubiquinone as a function of the methoxy orientation. Taken together with the already known influence of cofactor conformation on heme and chlorophyll electronic structure, it reveals a more widespread role for cofactor conformational control of electronic structure and associated electron transfer in biology.

  7. Structure and stabilization of hydrogen-rich transverse.

    Energy Technology Data Exchange (ETDEWEB)

    Lyra, Sgouria [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Wilde, B [Georgia Inst. of Technology, Atlanta, GA (United States); Kolla, Hemanth [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Seitzman, J. [Georgia Inst. of Technology, Atlanta, GA (United States); Lieuwen, T. C. [Georgia Inst. of Technology, Atlanta, GA (United States); Chen, Jacqueline H. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2014-07-01

    This paper reports the results of a joint experimental and numerical study of the ow characteristics and flame stabilization of a hydrogen rich jet injected normal to a turbulent, vitiated cross ow of lean methane combustion products. Simultaneous high-speed stereoscopic PIV and OH PLIF measurements were obtained and analyzed alongside three-dimensional direct numerical simulations of inert and reacting JICF with detailed H2/CO chemistry. Both the experiment and the simulation reveal that, contrary to most previous studies of reacting JICF stabilized in low-to-moderate temperature air cross ow, the present conditions lead to an autoigniting, burner-attached flame that initiates uniformly around the burner edge. Significant asymmetry is observed, however, between the reaction zones located on the windward and leeward sides of the jet, due to the substantially different scalar dissipation rates. The windward reaction zone is much thinner in the near field, while also exhibiting significantly higher local and global heat release than the much broader reaction zone found on the leeward side of the jet. The unsteady dynamics of the windward shear layer, which largely control the important jet/cross flow mixing processes in that region, are explored in order to elucidate the important flow stability implications arising in the reacting JICF. Vorticity spectra extracted from the windward shear layer reveal that the reacting jet is globally unstable and features two high frequency peaks, including a fundamental mode whose Strouhal number of ~0.7 agrees well with previous non-reacting JICF stability studies. The paper concludes with an analysis of the ignition, ame stabilization, and global structure of the burner-attached flame. Chemical explosive mode analysis (CEMA) shows that the entire windward shear layer, and a large region on the leeward side of the jet, are highly explosive prior to ignition and are dominated by non-premixed flame structures after

  8. Microwave-Assisted Extraction, Chemical Structures, and Chain Conformation of Polysaccharides from a Novel Cordyceps Sinensis Fungus UM01.

    Science.gov (United States)

    Cheong, Kit-Leong; Wang, Lan-Ying; Wu, Ding-Tao; Hu, De-Jun; Zhao, Jing; Li, Shao-Ping

    2016-09-01

    Cordyceps sinensis is a well-known tonic food with broad medicinal properties. The aim of the present study was to investigate the optimization of microwave-assisted extraction (MAE) and characterize chemical structures and chain conformation of polysaccharides from a novel C. sinensis fungus UM01. Ion-exchange and gel filtration chromatography were used to purify the polysaccharides. The chemical structure of purified polysaccharide was determined through gas chromatography-mass spectrometry. Moreover, high performance size exclusion chromatography combined with refractive index detector and multiangle laser light scattering were conducted to analyze the molecular weight (Mw ) and chain conformation of purified polysaccharide. Based on the orthogonal design L9 , optimal MAE conditions could be obtained through 1300 W of microwave power, with a 5-min irradiation time at a solid to water ratio of 1:60, generating the highest extraction yield of 6.20%. Subsequently, the polysaccharide UM01-S1 was purified. The UM01-S1 is a glucan-type polysaccharide with a (1→4)-β-d-glucosyl backbone and branching points located at O-3 of Glcp with a terminal-d-Glcp. The Mw , radius of gyration (Rg ) and hydrodynamic radius (Rh ) of UM01-S1 were determined as 5.442 × 10(6)  Da, 21.8 and 20.2 nm, respectively. Using the polymer solution theory, the exponent (ν) value of the power law function was calculated as 0.38, and the shape factor (ρ = Rg /Rh ) was 1.079, indicating that UM01-S1 has a sphere-like conformation with a branched structure in an aqueous solution. These results provide fundamental information for the future application of polysaccharides from cultured C. sinensis in health and functional food area. © 2016 Institute of Food Technologists®

  9. Decentralized stabilization of semi-active vibrating structures

    Science.gov (United States)

    Pisarski, Dominik

    2018-02-01

    A novel method of decentralized structural vibration control is presented. The control is assumed to be realized by a semi-active device. The objective is to stabilize a vibrating system with the optimal rates of decrease of the energy. The controller relies on an easily implemented decentralized switched state-feedback control law. It uses a set of communication channels to exchange the state information between the neighboring subcontrollers. The performance of the designed method is validated by means of numerical experiments performed for a double cantilever system equipped with a set of elastomers with controlled viscoelastic properties. In terms of the assumed objectives, the proposed control strategy significantly outperforms the passive damping cases and is competitive with a standard centralized control. The presented methodology can be applied to a class of bilinear control systems concerned with smart structural elements.

  10. Structural stability analysis considerations in fusion reactor plasma chamber design

    International Nuclear Information System (INIS)

    Delaney, M.J.; Cramer, B.A.

    1978-01-01

    This paper presents an approach to analyzing a toroidal plasma chamber for the prevention of both static and dynamic buckling. Results of stability analyses performed for the doublet shaped plasma chamber of the General Atomic 3.8 meter radius TNS ignition test reactor are presented. Load conditions are the static external atmospheric pressure load and the dynamic plasma disruption pulse load. Methods for analysis of plasma chamber structures are presented for both types of load. Analysis for static buckling is based on idealizing the plasma chamber into standard structural shapes and applying classical cylinder and circular torus buckling equations. Results are verified using the Buckling of Shells of Revolution (BOSOR4) finite difference computer code. Analysis for the dynamic loading is based on a pulse buckling analysis method for circular cylinders

  11. Preparation, structure and thermal stability of Cu/LDPE nanocomposites

    International Nuclear Information System (INIS)

    Xia Xianping; Cai Shuizhou; Xie Changsheng

    2006-01-01

    Copper/low-density-polyethylene (Cu/LDPE) nanocomposites have been prepared using a melt-blending technique in a single-screw extruder. Their structure and thermal characteristics are characterized by using X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (EDS), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The results of XRD, SEM and SEM-EDS Cu-mapping show that the nanocomposites are a hybrid of the polymer and the copper nanoparticles, and the copper nanoparticles aggregates were distributed uniformly in general. The results also show that the nanocomposites and the base resin, the pure LDPE, have a different crystalline structure and the same oriented characteristics owing to the presence of copper nanoparticles and the same cooling condition. The results of DSC show that the incorporation of copper nanoparticles can decrease the melting temperatures but increase the crystallization temperatures, and can lower the crystallinity degree of the matrix of the composites. The results of TGA show that the presence of copper nanoparticles can improve the thermal stability of the nanocomposites, a maximum increment of 18 deg. C is obtained comparing with the pure LDPE in this experiment. The results of TGA also show that the influence of the incorporation of the copper nanoparticles on the thermal stability of the Cu/LDPE nanocomposites is different from that of the non-metal nanoparticles on the polymer/non-metal nanocomposites and the copper microparticles on the Cu/LDPE microcomposites. The increase of the thermal stability of the Cu/LDPE nanocomposites will decrease when the content of the copper nanoparticles is more than 2 wt.%. The difference might be caused by the fact that the activity of the metal nanoparticles is much more higher than that of the non-metal nanoparticles, and the different size effect the different copper particles has

  12. Nonlinear Stability and Structure of Compressible Reacting Mixing Layers

    Science.gov (United States)

    Day, M. J.; Mansour, N. N.; Reynolds, W. C.

    2000-01-01

    The parabolized stability equations (PSE) are used to investigate issues of nonlinear flow development and mixing in compressible reacting shear layers. Particular interest is placed on investigating the change in flow structure that occurs when compressibility and heat release are added to the flow. These conditions allow the 'outer' instability modes- one associated with each of the fast and slow streams-to dominate over the 'central', Kelvin-Helmholtz mode that unaccompanied in incompressible nonreacting mixing layers. Analysis of scalar probability density functions in flows with dominant outer modes demonstrates the ineffective, one-sided nature of mixing that accompany these flow structures. Colayer conditions, where two modes have equal growth rate and the mixing layer is formed by two sets of vortices, offer some opportunity for mixing enhancement. Their extent, however, is found to be limited in the mixing layer's parameter space. Extensive validation of the PSE technique also provides a unique perspective on central- mode vortex pairing, further supporting the view that pairing is primarily governed perspective sheds insight on how linear stability theory is able to provide such an accurate prediction of experimentally-observed, fully nonlinear flow phenomenon.

  13. Seismic stability of a standalone glove box structure

    Energy Technology Data Exchange (ETDEWEB)

    Saraswat, A., E-mail: anupams@barc.gov.in [Bhabha Atomic Research Centre, Mumbai (India); Reddy, G.R. [Bhabha Atomic Research Centre, Mumbai (India); Ghosh, S. [Indian Institute of Technology Bombay, Mumbai (India); Ghosh, A.K.; Kumar, Arun [Bhabha Atomic Research Centre, Mumbai (India)

    2014-09-15

    Highlights: • Glove box is a leak tight, safety related structure used for handling radiotoxic materials. • To study the seismic performance of a freestanding glove box, extensive shake table testing has been carried out. • Glove box maintained structural integrity and leak tightness up to design basis earthquake loading. • Detailed three-dimensional finite element model of the structure is developed and analyzed by using direct time integration methods. • Simplified numerical method is proposed and successfully applied, to quickly estimate sliding displacement and determine upper bounds for it. - Abstract: In a nuclear fuel cycle facility, radiotoxic materials are being handled in freestanding leak tight enclosures called glove boxes (GBs). These glove boxes act as a primary confinement for the radiotoxic materials. Glove boxes are designed as per codal requirements for class I component. They are designed to withstand extreme level of earthquake loading with a return period of 10,000 years. To evaluate seismic performance of the glove box, there is a need to check the stability (sliding and overturning), structural integrity (stresses and strains) and leak tightness under earthquake loading. Extensive shake table experiments were conducted on a single standalone glove box. Actual laboratory conditions were simulated during testing to check the response. After extensive shake table testing, glove box structure was also analyzed using finite element (FE) software. Detailed three-dimensional model of glove box structure was developed and analyzed using nonlinear time history method. It was observed that finite element methods could be utilized to accurately predict dynamic response of glove box structure. This paper discusses the details and results of shake table testing and methodology used for modelling and analysing freestanding glove box structure under seismic loading. In addition, simplified numerical procedure, developed using energy conservation

  14. Seismic stability of a standalone glove box structure

    International Nuclear Information System (INIS)

    Saraswat, A.; Reddy, G.R.; Ghosh, S.; Ghosh, A.K.; Kumar, Arun

    2014-01-01

    Highlights: • Glove box is a leak tight, safety related structure used for handling radiotoxic materials. • To study the seismic performance of a freestanding glove box, extensive shake table testing has been carried out. • Glove box maintained structural integrity and leak tightness up to design basis earthquake loading. • Detailed three-dimensional finite element model of the structure is developed and analyzed by using direct time integration methods. • Simplified numerical method is proposed and successfully applied, to quickly estimate sliding displacement and determine upper bounds for it. - Abstract: In a nuclear fuel cycle facility, radiotoxic materials are being handled in freestanding leak tight enclosures called glove boxes (GBs). These glove boxes act as a primary confinement for the radiotoxic materials. Glove boxes are designed as per codal requirements for class I component. They are designed to withstand extreme level of earthquake loading with a return period of 10,000 years. To evaluate seismic performance of the glove box, there is a need to check the stability (sliding and overturning), structural integrity (stresses and strains) and leak tightness under earthquake loading. Extensive shake table experiments were conducted on a single standalone glove box. Actual laboratory conditions were simulated during testing to check the response. After extensive shake table testing, glove box structure was also analyzed using finite element (FE) software. Detailed three-dimensional model of glove box structure was developed and analyzed using nonlinear time history method. It was observed that finite element methods could be utilized to accurately predict dynamic response of glove box structure. This paper discusses the details and results of shake table testing and methodology used for modelling and analysing freestanding glove box structure under seismic loading. In addition, simplified numerical procedure, developed using energy conservation

  15. Flexible Near-Field Nanopatterning with Ultrathin, Conformal Phase Masks on Nonplanar Substrates for Biomimetic Hierarchical Photonic Structures.

    Science.gov (United States)

    Kwon, Young Woo; Park, Junyong; Kim, Taehoon; Kang, Seok Hee; Kim, Hyowook; Shin, Jonghwa; Jeon, Seokwoo; Hong, Suck Won

    2016-04-26

    Multilevel hierarchical platforms that combine nano- and microstructures have been intensively explored to mimic superior properties found in nature. However, unless directly replicated from biological samples, desirable multiscale structures have been challenging to efficiently produce to date. Departing from conventional wafer-based technology, new and efficient techniques suitable for fabricating bioinspired structures are highly desired to produce three-dimensional architectures even on nonplanar substrates. Here, we report a facile approach to realize functional nanostructures on uneven microstructured platforms via scalable optical fabrication techniques. The ultrathin form (∼3 μm) of a phase grating composed of poly(vinyl alcohol) makes the material physically flexible and enables full-conformal contact with rough surfaces. The near-field optical effect can be identically generated on highly curved surfaces as a result of superior conformality. Densely packed nanodots with submicron periodicity are uniformly formed on microlens arrays with a radius of curvature that is as low as ∼28 μm. Increasing the size of the gratings causes the production area to be successfully expanded by up to 16 in(2). The "nano-on-micro" structures mimicking real compound eyes are transferred to flexible and stretchable substrates by sequential imprinting, facilitating multifunctional optical films applicable to antireflective diffusers for large-area sheet-illumination displays.

  16. /sup 13/C-/sup 13/C spin-spin coupling constants in structural investigations. II. Conformational structure of vinyl ethers

    Energy Technology Data Exchange (ETDEWEB)

    Krivdin, L.B.; Shcherbakov, V.V.; Bzhezovskii, V.M.; Kalabin, G.A.

    1986-10-10

    The /sup 13/C-/sup 13/C spin-spin coupling constants between the carbon nuclei of the vinyl group were measured for a series of vinyl ethers. It was established that the unshared electron pairs of the oxygen atom can make a substantial stereospecific contribution to the direct /sup 13/C-/sup 13/C constants of the adjacent nuclei. The observed effect was used to establish the conformational structure of the compounds.

  17. Assessing the factor structures of the 55- and 22-item versions of the conformity to masculine norms inventory.

    Science.gov (United States)

    Owen, Jesse

    2011-03-01

    The current study examined the psychometric properties of the abbreviated versions, 55- and 22-items, of the Conformity to Masculine Norms Inventory (CMNI). The authors tested the factor structure for the 11 subscales of the CMNI-55 and the global masculinity factor for the CMNI-55 and the CMNI-22. In a clinical sample of men and women (n=522), the results supported the 11-factor model. Furthermore, the factor structure was invariant for men and women. The higher order model, which tested the utility of the global masculine score, demonstrated marginal fit. The factor structures for the global masculinity score for the CMNI-22 demonstrated poor fit. Collectively, the results suggest that the CMNI-55 is better represented in a multidimensional construct. The subscales' alpha levels and factor loadings were, generally, within acceptable limits. Gender and ethnic mean level differences are also reported. © The Author(s) 2011

  18. New conformations of linear polyubiquitin chains from crystallographic and solution-scattering studies expand the conformational space of polyubiquitin.

    Science.gov (United States)

    Thach, Trung Thanh; Shin, Donghyuk; Han, Seungsu; Lee, Sangho

    2016-04-01

    The conformational flexibility of linkage-specific polyubiquitin chains enables ubiquitylated proteins and their receptors to be involved in a variety of cellular processes. Linear or Met1-linked polyubiquitin chains, associated with nondegradational cellular signalling pathways, have been known to adopt multiple conformations from compact to extended conformations. However, the extent of such conformational flexibility remains open. Here, the crystal structure of linear Ub2 was determined in a more compact conformation than that of the previously known structure (PDB entry 3axc). The two structures differ significantly from each other, as shown by an r.m.s.d. between C(α) atoms of 3.1 Å. The compactness of the linear Ub2 structure in comparison with PDB entry 3axc is supported by smaller values of the radius of gyration (Rg; 18 versus 18.9 Å) and the maximum interatomic distance (Dmax; 55.5 versus 57.8 Å). Extra intramolecular hydrogen bonds formed among polar residues between the distal and proximal ubiquitin moieties seem to contribute to stabilization of the compact conformation of linear Ub2. An ensemble of three semi-extended and extended conformations of linear Ub2 was also observed by small-angle X-ray scattering (SAXS) analysis in solution. In addition, the conformational heterogeneity in linear polyubiquitin chains is clearly manifested by SAXS analyses of linear Ub3 and Ub4: at least three distinct solution conformations are observed in each chain, with the linear Ub3 conformations being compact. The results expand the extent of conformational space of linear polyubiquitin chains and suggest that changes in the conformational ensemble may be pivotal in mediating multiple signalling pathways.

  19. The Crystal Structure and Conformations of an Unbranched Mixed Tri-Ubiquitin Chain Containing K48 and K63 Linkages.

    Science.gov (United States)

    Padala, Prasanth; Soudah, Nadine; Giladi, Moshe; Haitin, Yoni; Isupov, Michail N; Wiener, Reuven

    2017-12-08

    The ability of ubiquitin to function in a wide range of cellular processes is ascribed to its capacity to cause a diverse spectrum of modifications. While a target protein can be modified with monoubiquitin, it can also be modified with ubiquitin chains. The latter include seven types of homotypic chains as well as mixed ubiquitin chains. In a mixed chain, not all the isopeptide bonds are restricted to a specific lysine of ubiquitin, resulting in a chain possessing more than one type of linkage. While structural characterization of homotypic chains has been well elucidated, less is known about mixed chains. Here we present the crystal structure of a mixed tri-ubiquitin chain at 3.1-Å resolution. In the structure, the proximal ubiquitin is connected to the middle ubiquitin via K48 and these two ubiquitins adopt a compact structure as observed in K48 di-ubiquitin. The middle ubiquitin links to the distal ubiquitin via its K63 and these ubiquitins adopt two conformations, suggesting a flexible structure. Using small-angle X-ray scattering, we unexpectedly found differences between the conformational ensembles of the above tri-ubiquitin chains and chains possessing the same linkages but in the reverse order. In addition, cleavage of the K48 linkage by DUB is faster if this linkage is at the distal end. Taken together, our results suggest that in mixed chains, not only the type of the linkages but also their sequence determine the structural and functional properties of the chain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Conformal house

    DEFF Research Database (Denmark)

    Ryttov, Thomas Aaby; Sannino, Francesco

    2010-01-01

    fixed point. As a consistency check we recover the previously investigated bounds of the conformal windows when restricting to a single matter representation. The earlier conformal windows can be imagined to be part now of the new conformal house. We predict the nonperturbative anomalous dimensions...... at the infrared fixed points. We further investigate the effects of adding mass terms to the condensates on the conformal house chiral dynamics and construct the simplest instanton induced effective Lagrangian terms...

  1. The Fab Conformations in the Solution Structure of Human Immunoglobulin G4 (IgG4) Restrict Access to Its Fc Region

    Science.gov (United States)

    Rayner, Lucy E.; Hui, Gar Kay; Gor, Jayesh; Heenan, Richard K.; Dalby, Paul A.; Perkins, Stephen J.

    2014-01-01

    Human IgG4 antibody shows therapeutically useful properties compared with the IgG1, IgG2, and IgG3 subclasses. Thus IgG4 does not activate complement and shows conformational variability. These properties are attributable to its hinge region, which is the shortest of the four IgG subclasses. Using high throughput scattering methods, we studied the solution structure of wild-type IgG4(Ser222) and a hinge mutant IgG4(Pro222) in different buffers and temperatures where the proline substitution suppresses the formation of half-antibody. Analytical ultracentrifugation showed that both IgG4 forms were principally monomeric with sedimentation coefficients s20,w0 of 6.6–6.8 S. A monomer-dimer equilibrium was observed in heavy water buffer at low temperature. Scattering showed that the x-ray radius of gyration Rg was unchanged with concentration in 50–250 mm NaCl buffers, whereas the neutron Rg values showed a concentration-dependent increase as the temperature decreased in heavy water buffers. The distance distribution curves (P(r)) revealed two peaks, M1 and M2, that shifted below 2 mg/ml to indicate concentration-dependent IgG4 structures in addition to IgG4 dimer formation at high concentration in heavy water. Constrained x-ray and neutron scattering modeling revealed asymmetric solution structures for IgG4(Ser222) with extended hinge structures. The IgG4(Pro222) structure was similar. Both IgG4 structures showed that their Fab regions were positioned close enough to the Fc region to restrict C1q binding. Our new molecular models for IgG4 explain its inability to activate complement and clarify aspects of its stability and function for therapeutic applications. PMID:24876381

  2. Correlating the Impact of Well-Defined Oligosaccharide Structures on Physical Stability Profiles of IgG1-Fc Glycoforms.

    Science.gov (United States)

    More, Apurva S; Toprani, Vishal M; Okbazghi, Solomon Z; Kim, Jae H; Joshi, Sangeeta B; Middaugh, C Russell; Tolbert, Thomas J; Volkin, David B

    2016-02-01

    As part of a series of articles in this special issue describing 4 well-defined IgG1-Fc glycoforms as a model system for biosimilarity analysis (high mannose-Fc, Man5-Fc, GlcNAc-Fc and N297Q-Fc aglycosylated), the focus of this work is comparisons of their physical properties. A trend of decreasing apparent solubility (thermodynamic activity) by polyethylene glycol precipitation (pH 4.5, 6.0) and lower conformational stability by differential scanning calorimetry (pH 4.5) was observed with reducing size of the N297-linked oligosaccharide structures. Using multiple high-throughput biophysical techniques, the physical stability of the Fc glycoproteins was then measured in 2 formulations (NaCl and sucrose) across a wide range of temperatures (10°C-90°C) and pH (4.0-7.5) conditions. The data sets were used to construct 3-index empirical phase diagrams and radar charts to visualize the regions of protein structural stability. Each glycoform showed improved stability in the sucrose (vs. salt) formulation. The HM-Fc and Man5-Fc displayed the highest relative stability, followed by GlcNAc-Fc, with N297Q-Fc being the least stable. Thus, the overall physical stability profiles of the 4 IgG1-Fc glycoforms also show a correlation with oligosaccharide structure. These data sets are used to develop a mathematical model for biosimilarity analysis (as described in a companion article by Kim et al. in this issue). Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. Deletion of intragenic tandem repeats in unit C of FLO1 of Saccharomyces cerevisiae increases the conformational stability of flocculin under acidic and alkaline conditions.

    Directory of Open Access Journals (Sweden)

    Ee Li

    Full Text Available Flocculation is an attractive property for Saccaromyces cerevisiae, which plays important roles in fermentation industry and environmental remediation. The process of flocculation is mediated by a family of cell surface flocculins. As one member of flocculins, Flo1 is characterized by four families of repeats (designated as repeat units A, B, C and D in the central domain. It is generally accepted that variation of repeat unit A in length in Flo1 influences the degree of flocculation or specificity for sugar recognization. However, no reports were observed for other repeat units. Here, we compared the flocculation ability and its sensitivity to environmental factors between yeast strain YSF1 carrying the intact FLO1 gene and yeast strains carrying the derived forms of FLO1 with partial or complete deletion of repeats in unit C. No obvious differences in flocculation ability and specificity of carbohydrate recognition were observed among these yeast strains, which indicates the truncated flocculins can stride across the cell wall and cluster the N-terminal domain on the surface of yeast cells as the intact Flo1 thereby improving intercellular binding. However, yeast strains with the truncated flocculins required more mannose to inhibit completely the flocculation, displayed broad tolerance of flocculation to pH fluctuation, and the fewer the repeats in unit C, the stronger adaptability of flocculation to pH change, which was not relevant to the position of deletion. This suggests that more stable active conformation is obtained for flocculin by deletion the repeat unit C in the central domain of Flo1, which was validated further by the higher hydrophobicity on the surface of cells of YSF1c with complete deletion of unit C under neutral and alkaline conditions and the stabilization of GFP conformation by fusion with flocculin with complete deletion of unit C in the central domain.

  4. ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters.

    Science.gov (United States)

    Hanukoglu, Israel

    2017-02-01

    The acid-sensing ion channels (ASICs) and epithelial sodium channels (ENaC) are members of a superfamily of channels that play critical roles in mechanosensation, chemosensation, nociception, and regulation of blood volume and pressure. These channels look and function like a tripartite funnel that directs the flow of Na + ions into the cytoplasm via the channel pore in the membrane. The subunits that form these channels share a common structure with two transmembrane segments (TM1 and TM2) and a large extracellular part. In most vertebrates, there are five paralogous genes that code for ASICs (ASIC1-ASIC5), and four for ENaC subunits alpha, beta, gamma, and delta (α, β, γ, and δ). While ASICs can form functional channels as a homo- or heterotrimer, ENaC functions as an obligate heterotrimer composed of α-β-γ or β-γ-δ subunits. The structure of ASIC has been determined in several conformations, including desensitized and open states. This review presents a comparison of the structures of these states using easy-to-understand molecular models of the full complex, the central tunnel that includes an outer vestibule, the channel pore, and ion selectivity filter. The differences in the secondary, tertiary, and quaternary structures of the states are summarized to pinpoint the conformational changes responsible for channel opening. Results of site-directed mutagenesis studies of ENaC subunits are examined in light of ASIC1 models. Based on these comparisons, a molecular model for the selectivity filter of ENaC is built by in silico mutagenesis of an ASIC1 structure. These models suggest that Na + ions pass through the filter in a hydrated state. © 2016 Federation of European Biochemical Societies.

  5. Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration

    Energy Technology Data Exchange (ETDEWEB)

    He, Huawei; Yang, Taehong; Terman, Jonathan R.; Zhang, Xuewu; (UTSMC)

    2010-01-20

    Plexin cell surface receptors bind to semaphorin ligands and transduce signals for regulating neuronal axon guidance. The intracellular region of plexins is essential for signaling and contains a R-Ras/M-Ras GTPase activating protein (GAP) domain that is divided into two segments by a Rho GTPase-binding domain (RBD). The regulation mechanisms for plexin remain elusive, although it is known that activation requires both binding of semaphorin to the extracellular region and a Rho-family GTPase (Rac1 or Rnd1) to the RBD. Here we report the crystal structure of the plexin A3 intracellular region. The structure shows that the N- and C-terminal portions of the GAP homologous regions together form a GAP domain with an overall fold similar to other Ras GAPs. However, the plexin GAP domain adopts a closed conformation and cannot accommodate R-Ras/M-Ras in its substrate-binding site, providing a structural basis for the autoinhibited state of plexins. A comparison with the plexin B1 RBD/Rnd1 complex structure suggests that Rnd1 binding alone does not induce a conformational change in plexin, explaining the requirement of both semaphorin and a Rho GTPase for activation. The structure also identifies an N-terminal segment that is important for regulation. Both the N-terminal segment and the RBD make extensive interactions with the GAP domain, suggesting the presence of an allosteric network connecting these three domains that integrates semaphorin and Rho GTPase signals to activate the GAP. The importance of these interactions in plexin signaling is shown by both cell-based and in vivo axon guidance assays.

  6. Structure and Stability of Deflagrations in Porous Energetic Materials

    Energy Technology Data Exchange (ETDEWEB)

    stephen B. Margolis; Forman A. Williams

    1999-03-01

    Theoretical two-phase-flow analyses have recently been developed to describe the structure and stability of multi-phase deflagrations in porous energetic materials, in both confined and unconfined geometries. The results of these studies are reviewed, with an emphasis on the fundamental differences that emerge with respect to the two types of geometries. In particular, pressure gradients are usually negligible in unconfined systems, whereas the confined problem is generally characterized by a significant gas-phase pressure difference, or overpressure, between the burned and unburned regions. The latter leads to a strong convective influence on the burning rate arising from the pressure-driven permeation of hot gases into the solid/gas region and the consequent preheating of the unburned material. It is also shown how asymptotic models that are suitable for analyzing stability may be derived based on the largeness of an overall activation-energy parameter. From an analysis of such models, it is shown that the effects of porosity and two-phase flow are generally destabilizing, suggesting that degraded propellants, which exhibit greater porosity than their pristine counterparts, may be more readily subject to combustion instability and nonsteady deflagration.

  7. STRUCTURAL STABILITY OF HIGH NITROGEN AUSTENITIC STAINLESS STEELS

    Directory of Open Access Journals (Sweden)

    Jana Bakajová

    2011-05-01

    Full Text Available This paper deals with the structural stability of an austenitic stainless steel with high nitrogen content. The investigated steel was heat treated at 800°C using different annealing times. Investigation was carried out using light microscopy, transmission electron microscopy and thermodynamic calculations. Three phases were identified by electron diffraction: Cr2N, sigma – phase and M23C6. The thermodynamic prediction is in good agreement with the experimental result. The only is the M23C6 carbide phase which is not thermodynamically predicted. Cr2N is the majority secondary phase and occurs in the form of discrete particles or cells (lamellas of Cr2N and austenite.

  8. Enhanced structural stability of DNA origami nanostructures by graphene encapsulation

    International Nuclear Information System (INIS)

    Matković, Aleksandar; Vasić, Borislav; Pešić, Jelena; Gajić, Radoš; Prinz, Julia; Bald, Ilko; Milosavljević, Aleksandar R

    2016-01-01

    We demonstrate that a single-layer graphene replicates the shape of DNA origami nanostructures very well. It can be employed as a protective layer for the enhancement of structural stability of DNA origami nanostructures. Using the AFM based manipulation, we show that the normal force required to damage graphene encapsulated DNA origami nanostructures is over an order of magnitude greater than for the unprotected ones. In addition, we show that graphene encapsulation offers protection to the DNA origami nanostructures against prolonged exposure to deionized water, and multiple immersions. Through these results we demonstrate that graphene encapsulated DNA origami nanostructures are strong enough to sustain various solution phase processing, lithography and transfer steps, thus extending the limits of DNA-mediated bottom-up fabrication. (paper)

  9. Hydrolytic catalysis and structural stabilization in a designed metalloprotein

    Science.gov (United States)

    Zastrow, Melissa L.; Peacock, Anna F. A.; Stuckey, Jeanne A.; Pecoraro, Vincent L.

    2011-01-01

    Metal ions are an important part of many natural proteins, providing structural, catalytic and electron transfer functions. Reproducing these functions in a designed protein is the ultimate challenge to our understanding of them. Here, we present an artificial metallohydrolase, which has been shown by X-ray crystallography to contain two different metal ions – a Zn(II) ion which is important for catalytic activity and a Hg(II) ion which provides structural stability. This metallohydrolase displays catalytic activity that compares well with several characteristic reactions of natural enzymes. It catalyses p-nitrophenyl acetate hydrolysis (pNPA) to within ~100-fold of the efficiency of human carbonic anhydrase (CA)II and is at least 550-fold better than comparable synthetic complexes. Similarly, CO2 hydration occurs with an efficiency within ~500-fold of CAII. While histidine residues in the absence of Zn(II) exhibit pNPA hydrolysis, miniscule apopeptide activity is observed for CO2 hydration. The kinetic and structural analysis of this first de novo designed hydrolytic metalloenzyme uncovers necessary design features for future metalloenzymes containing one or more metals. PMID:22270627

  10. Structures of Rotavirus Reassortants Demonstrate Correlation of Altered Conformation of the VP4 Spike and Expression of Unexpected VP4-Associated Phenotypes

    Science.gov (United States)

    Pesavento, Joseph B.; Billingsley, Angela M.; Roberts, Ed J.; Ramig, Robert F.; Prasad, B. V. Venkataram

    2003-01-01

    Numerous prior studies have indicated that viable rotavirus reassortants containing structural proteins of heterologous parental origin may express unexpected phenotypes, such as changes in infectivity and immunogenicity. To provide a structural basis for alterations in phenotypic expression, a three-dimensional structural analysis of these reassortants was conducted. The structures of the reassortants show that while VP4 generally maintains the parental structure when moved to a heterologous protein background, in certain reassortants, there are subtle alterations in the conformation of VP4. The alterations in VP4 conformation correlated with expression of unexpected VP4-associated phenotypes. Interactions between heterologous VP4 and VP7 in reassortants expressing unexpected phenotypes appeared to induce the conformational alterations seen in VP4. PMID:12584352

  11. DNA secondary structures: stability and function of G-quadruplex structures

    Science.gov (United States)

    Bochman, Matthew L.; Paeschke, Katrin; Zakian, Virginia A.

    2013-01-01

    In addition to the canonical double helix, DNA can fold into various other inter- and intramolecular secondary structures. Although many such structures were long thought to be in vitro artefacts, bioinformatics demonstrates that DNA sequences capable of forming these structures are conserved throughout evolution, suggesting the existence of non-B-form DNA in vivo. In addition, genes whose products promote formation or resolution of these structures are found in diverse organisms, and a growing body of work suggests that the resolution of DNA secondary structures is critical for genome integrity. This Review focuses on emerging evidence relating to the characteristics of G-quadruplex structures and the possible influence of such structures on genomic stability and cellular processes, such as transcription. PMID:23032257

  12. Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

    Science.gov (United States)

    Regad, Leslie; Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

    2017-01-01

    Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels.

  13. Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

    Directory of Open Access Journals (Sweden)

    Leslie Regad

    Full Text Available Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC, obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at

  14. Structural ordering of disordered ligand-binding loops of biotin protein ligase into active conformations as a consequence of dehydration.

    Directory of Open Access Journals (Sweden)

    Vibha Gupta

    Full Text Available Mycobacterium tuberculosis (Mtb, a dreaded pathogen, has a unique cell envelope composed of high fatty acid content that plays a crucial role in its pathogenesis. Acetyl Coenzyme A Carboxylase (ACC, an important enzyme that catalyzes the first reaction of fatty acid biosynthesis, is biotinylated by biotin acetyl-CoA carboxylase ligase (BirA. The ligand-binding loops in all known apo BirAs to date are disordered and attain an ordered structure only after undergoing a conformational change upon ligand-binding. Here, we report that dehydration of Mtb-BirA crystals traps both the apo and active conformations in its asymmetric unit, and for the first time provides structural evidence of such transformation. Recombinant Mtb-BirA was crystallized at room temperature, and diffraction data was collected at 295 K as well as at 120 K. Transfer of crystals to paraffin and paratone-N oil (cryoprotectants prior to flash-freezing induced lattice shrinkage and enhancement in the resolution of the X-ray diffraction data. Intriguingly, the crystal lattice rearrangement due to shrinkage in the dehydrated Mtb-BirA crystals ensued structural order of otherwise flexible ligand-binding loops L4 and L8 in apo BirA. In addition, crystal dehydration resulted in a shift of approximately 3.5 A in the flexible loop L6, a proline-rich loop unique to Mtb complex as well as around the L11 region. The shift in loop L11 in the C-terminal domain on dehydration emulates the action responsible for the complex formation with its protein ligand biotin carboxyl carrier protein (BCCP domain of ACCA3. This is contrary to the involvement of loop L14 observed in Pyrococcus horikoshii BirA-BCCP complex. Another interesting feature that emerges from this dehydrated structure is that the two subunits A and B, though related by a noncrystallographic twofold symmetry, assemble into an asymmetric dimer representing the ligand-bound and ligand-free states of the protein, respectively. In

  15. Structure validation of the Josephin domain of ataxin-3: Conclusive evidence for an open conformation

    International Nuclear Information System (INIS)

    Nicastro, Giuseppe; Habeck, Michael; Masino, Laura; Svergun, Dmitri I.; Pastore, Annalisa

    2006-01-01

    The availability of new and fast tools in structure determination has led to a more than exponential growth of the number of structures solved per year. It is therefore increasingly essential to assess the accuracy of the new structures by reliable approaches able to assist validation. Here, we discuss a specific example in which the use of different complementary techniques, which include Bayesian methods and small angle scattering, resulted essential for validating the two currently available structures of the Josephin domain of ataxin-3, a protein involved in the ubiquitin/proteasome pathway and responsible for neurodegenerative spinocerebellar ataxia of type 3. Taken together, our results demonstrate that only one of the two structures is compatible with the experimental information. Based on the high precision of our refined structure, we show that Josephin contains an open cleft which could be directly implicated in the interaction with polyubiquitin chains and other partners

  16. Insight into the conformational stability of membrane-embedded BamA using a combined solution and solid-state NMR approach

    Energy Technology Data Exchange (ETDEWEB)

    Sinnige, Tessa; Houben, Klaartje [Utrecht University, NMR Spectroscopy, Department of Chemistry, Faculty of Science, Bijvoet Center for Biomolecular Research (Netherlands); Pritisanac, Iva [Physical and Theoretical Chemistry Laboratory (United Kingdom); Renault, Marie [Institute of Pharmacology and Structural Biology (France); Boelens, Rolf; Baldus, Marc, E-mail: m.baldus@uu.nl [Utrecht University, NMR Spectroscopy, Department of Chemistry, Faculty of Science, Bijvoet Center for Biomolecular Research (Netherlands)

    2015-04-15

    The β-barrel assembly machinery (BAM) is involved in folding and insertion of outer membrane proteins in Gram-negative bacteria, a process that is still poorly understood. With its 790 residues, BamA presents a challenge to current NMR methods. We utilized a “divide and conquer” approach in which we first obtained resonance assignments for BamA’s periplasmic POTRA domains 4 and 5 by solution NMR. Comparison of these assignments to solid-state NMR (ssNMR) data obtained on two BamA constructs including the transmembrane domain and one or two soluble POTRA domains suggested that the fold of POTRA domain 5 critically depends on the interface with POTRA 4. Using specific labeling schemes we furthermore obtained ssNMR resonance assignments for residues in the extracellular loop 6 that is known to be crucial for BamA-mediated substrate folding and insertion. Taken together, our data provide novel insights into the conformational stability of membrane-embedded, non-crystalline BamA.

  17. Conformational Sampling in Template-Free Protein Loop Structure Modeling: An Overview

    OpenAIRE

    Li, Yaohang

    2013-01-01

    Accurately modeling protein loops is an important step to predict three-dimensional structures as well as to understand functions of many proteins. Because of their high flexibility, modeling the three-dimensional structures of loops is difficult and is usually treated as a “mini protein folding problem” under geometric constraints. In the past decade, there has been remarkable progress in template-free loop structure modeling due to advances of computational methods as well as stably increas...

  18. Crystal structure, conformational analysis, and molecular dynamics of tetra-0-methyl-(+)-catechin

    Science.gov (United States)

    Frank R. Fronczek; Richard W. Hemingway; G. Wayne McGraw; Jan P. Steynberg; Carin A. Helfer; Wayne L. Mattice

    1993-01-01

    The structure of tetra-O-methyl-(+)-catechin has been determined in the crystalline state. Two independent molecules, denoted structure A and structure B, exist in the unit cell. Crystals are triclinic, space group P1, a=4.8125(2) Ǻ, b=12.9148(8) Ǻ, c=13.8862(11) Ǻ, α=86.962(6)°, β=89.120(5)°, γ=...

  19. Structure of conjugated polyketone reductase from Candida parapsilosis IFO 0708 reveals conformational changes for substrate recognition upon NADPH binding.

    Science.gov (United States)

    Qin, Hui-Min; Yamamura, Akihiro; Miyakawa, Takuya; Kataoka, Michihiko; Nagai, Takahiro; Kitamura, Nahoko; Urano, Nobuyuki; Maruoka, Shintaro; Ohtsuka, Jun; Nagata, Koji; Shimizu, Sakayu; Tanokura, Masaru

    2014-01-01

    Conjugated polyketone reductase C2 (CPR-C2) from Candida parapsilosis IFO 0708, identified as a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent ketopantoyl lactone reductase, belongs to the aldo-keto reductase superfamily. This enzyme reduces ketopantoyl lactone to D-pantoyl lactone in a strictly stereospecific manner. To elucidate the structural basis of the substrate specificity, we determined the crystal structures of the apo CPR-C2 and CPR-C2/NADPH complex at 1.70 and 1.80 Å resolutions, respectively. CPR-C2 adopted a triose-phosphate isomerase barrel fold at the core of the structure. Binding with the cofactor NADPH induced conformational changes in which Thr27 and Lys28 moved 15 and 5.0 Å, respectively, in the close vicinity of the adenosine 2'-phosphate group of NADPH to form hydrogen bonds. Based on the comparison of the CPR-C2/NADPH structure with 3-α-hydroxysteroid dehydrogenase and mutation analyses, we constructed substrate binding models with ketopantoyl lactone, which provided insight into the substrate specificity by the cofactor-induced structure. The results will be useful for the rational design of CPR-C2 mutants targeted for use in the industrial manufacture of ketopantoyl lactone.

  20. Molecular dynamics studies of the conformation of sorbitol

    Science.gov (United States)

    Lerbret, A.; Mason, P.E.; Venable, R.M.; Cesàro, A.; Saboungi, M.-L.; Pastor, R.W.; Brady, J.W.

    2009-01-01

    Molecular dynamics simulations of a 3 m aqueous solution of D-sorbitol (also called D-glucitol) have been performed at 300 K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2–C-3 torsion (spanned by the O-2–O-4 hydrogen bond), where the NMR data supports a more bent structure. PMID:19744646

  1. Structurally stabilized organosilane-templated thermostable mesoporous titania.

    Science.gov (United States)

    Amoli, Vipin; Tiwari, Rashmi; Dutta, Arghya; Bhaumik, Asim; Sinha, Anil Kumar

    2014-01-13

    Structurally thermostable mesoporous anatase TiO2 (m-TiO2) nanoparticles, uniquely decorated with atomically dispersed SiO2, is reported for the first time. The inorganic Si portion of the novel organosilane template, used as a mesopores-directing agent, is found to be incorporated in the pore walls of the titania aggregates, mainly as isolated sites. This is evident by transmission electron microscopy and high-angle annular dark field scanning transmission electron microscopy, combined with electron dispersive X-ray spectroscopy. This type of unique structure provides exceptional stability to this new material against thermal collapse of the mesoporous structure, which is reflected in its high surface area (the highest known for anatase titania), even after high-temperature (550 °C) calcination. Control of crystallite size, pore diameter, and surface area is achieved by varying the molar ratios of the titanium precursor and the template during synthesis. These mesoporous materials retain their porosity and high surface area after template removal and further NaOH/HCl treatment to remove silica. We investigate their performance for dye-sensitized solar cells (DSSCs) with bilayer TiO2 electrodes, which are prepared by applying a coating of m-TiO2 onto a commercial titania (P25) film. The high surface area of the upper mesoporous layer in the P25-m-TiO2 DSSC significantly increases the dye loading ability of the photoanode. The photocurrent and fill factor for the DSSC with the bilayer TiO2 electrode are greatly improved. The large increase in photocurrent current (ca. 56%) in the P25-m-TiO2 DSSC is believed to play a significant role in achieving a remarkable increase in the photovoltaic efficiency (60%) of the device, compared to DSSCs with a monolayer of P25 as the electrode. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Conformational Effects through Hydrogen Bonding in a Constrained γ-Peptide Template: From Intraresidue Seven-Membered Rings to a Gel-Forming Sheet Structure.

    Science.gov (United States)

    Awada, Hawraà; Grison, Claire M; Charnay-Pouget, Florence; Baltaze, Jean-Pierre; Brisset, François; Guillot, Régis; Robin, Sylvie; Hachem, Ali; Jaber, Nada; Naoufal, Daoud; Yazbeck, Ogaritte; Aitken, David J

    2017-05-05

    A series of three short oligomers (di-, tri-, and tetramers) of cis-2-(aminomethyl)cyclobutane carboxylic acid, a γ-amino acid featuring a cyclobutane ring constraint, were prepared, and their conformational behavior was examined spectroscopically and by molecular modeling. In dilute solutions, these peptides showed a number of low-energy conformers, including ribbonlike structures pleated around a rarely observed series of intramolecular seven-membered hydrogen bonds. In more concentrated solutions, these interactions defer to an organized supramolecular assembly, leading to thermoreversible organogel formation notably for the tripeptide, which produced fibrillar xerogels. In the solid state, the dipeptide adopted a fully extended conformation featuring a one-dimensional network of intermolecularly H-bonded molecules stacked in an antiparallel sheet alignment. This work provides unique insight into the interplay between inter- and intramolecular H-bonded conformer topologies for the same peptide template.

  3. X-ray and 1H-NMR spectroscopic studies of the structures and conformations of the new nootropic agents RU-35929, RU-47010 and RU-35965

    Science.gov (United States)

    Amato, Maria E.; Bandoli, Giuliano; Casellato, Umberto; Pappalardo, Giuseppe C.; Toja, Emilio

    1990-10-01

    The crystal and molecular structures of the nootropics (±)1-benzenesulphonyl-2-oxo-5-ethoxypyrrolidine ( 1), (±)1-(3-pyridinylsulphonyl)-2-oxo-5-ethoxypyrrolidine ( 2) and (±)1-benzenesulphonyl-2-oxo-5-isopropyloxypyrrolidine ( 3) have been determined by X-ray analysis. The solution conformation of 1, 2 and 3 has been investigated by 1H NMR spectroscopy. In the solid state, the main feature consists of the similar structural parameters and conformations, with the exception of the conformation adopted by the 5-ethoxy moiety which changes on passing from 1 to 2. The solid state overall enveloped conformation of the 2-pyrrolidinone ring for the three nootropics is found to be retained in solution on the basis of NMR evidence. Comparison between calculated and experimental coupling constant values shows that one of the two possible puckered opposite conformational isomers (half-chair shapes) occurs in solution. The relative pharmacological potencies of 1, 2 and 3 cannot therefore be interpreted in terms of the different conformation features presently detectable by available experimental methods.

  4. Transportation Conformity

    Science.gov (United States)

    This section provides information on: current laws, regulations and guidance, policy and technical guidance, project-level conformity, general information, contacts and training, adequacy review of SIP submissions

  5. Conformal invariance in supergravity

    International Nuclear Information System (INIS)

    Bergshoeff, E.A.

    1983-01-01

    In this thesis the author explains the role of conformal invariance in supergravity. He presents the complete structure of extended conformal supergravity for N <= 4. The outline of this work is as follows. In chapter 2 he briefly summarizes the essential properties of supersymmetry and supergravity and indicates the use of conformal invariance in supergravity. The idea that the introduction of additional symmetry transformations can make clear the structure of a field theory is not reserved to supergravity only. By means of some simple examples it is shown in chapter 3 how one can always introduce additional gauge transformations in a theory of massive vector fields. Moreover it is shown how the gauge invariant formulation sometimes explains the quantum mechanical properties of the theory. In chapter 4 the author defines the conformal transformations and summarizes their main properties. He explains how these conformal transformations can be used to analyse the structure of gravity. The supersymmetric extension of these results is discussed in chapter 5. Here he describes as an example how N=1 supergravity can be reformulated in a conformally-invariant way. He also shows that beyond N=1 the gauge fields of the superconformal symmetries do not constitute an off-shell field representation of extended conformal supergravity. Therefore, in chapter 6, a systematic method to construct the off-shell formulation of all extended conformal supergravity theories with N <= 4 is developed. As an example he uses this method to construct N=1 conformal supergravity. Finally, in chapter 7 N=4 conformal supergravity is discussed. (Auth.)

  6. Constraints on the nature of inertial motion arising from the universality of free fall and the conformal causal structure of space-time

    International Nuclear Information System (INIS)

    Coleman, R.A.; Korte, H.

    1984-01-01

    According to the principle of the universality of free fall, the motions of all neutral monopole particles are governed by one common path structure. This principle does not, however, require the path structure to be geodesic; that is, the path structure need not be a projective structure. It is shown that any equation of motion structure (either a curve or a path structure) that has sufficient microisotropy to be compatible with the conformal causal structure of space-time must be geodesic and must be unique. Hence, the empirically well-supported principles of conformal causality and of the universality of free fall together require the existence of a unique Weyl structure on space-time

  7. Structural analysis of prolyl oligopeptidases using molecular docking and dynamics: insights into conformational changes and ligand binding.

    Directory of Open Access Journals (Sweden)

    Swati Kaushik

    Full Text Available Prolyl oligopeptidase (POP is considered as an important pharmaceutical target for the treatment of numerous diseases. Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, human and A. thaliana. Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, human POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in human context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of molecular dynamics (MD simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in β-propeller pore size, which was found to be hidden by five lysine residues present on blades one and seven. During simulation, β-propeller pore size was increased by ∼2 Å in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in human and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several neurodegenerative diseases.

  8. Conformal special relativity

    International Nuclear Information System (INIS)

    Maia, M.D.

    2006-01-01

    It is shown that the information loss/recovery theorem based on the ADS/CFT correspondence is not consistent with the stability of the Schwarzschild or Reissner-Nordstrom black holes. Nonetheless, the conformal invariance of Yang-Mills theory points to new relativity principle compatible with quantum unitarity near those black holes

  9. DFT approach to (benzylthio)acetic acid: Conformational search, molecular (monomer and dimer) structure, vibrational spectroscopy and some electronic properties

    Science.gov (United States)

    Sienkiewicz-Gromiuk, Justyna

    2018-01-01

    The DFT studies were carried out with the B3LYP method utilizing the 6-31G and 6-311++G(d,p) basis sets depending on whether the aim of calculations was to gain the geometry at equilibrium, or to calculate the optimized molecular structure of (benzylthio)acetic acid (Hbta) in the forms of monomer and dimer. The minimum conformational energy search was followed by the potential energy surface (PES) scan of all rotary bonds existing in the acid molecule. The optimized geometrical monomeric and dimeric structures of the title compound were compared with the experimental structural data in the solid state. The detailed vibrational interpretation of experimental infrared and Raman bands was performed on the basis of theoretically simulated ESFF-scaled wavenumbers calculated for the monomer and dimer structures of Hbta. The electronic characteristics of Hbta is also presented in terms of Mulliken atomic charges, frontier molecular orbitals and global reactivity descriptors. Additionally, the MEP and ESP surfaces were computed to predict coordination sites for potential metal complex formation.

  10. SL1 revisited: functional analysis of the structure and conformation of HIV-1 genome RNA.

    Science.gov (United States)

    Sakuragi, Sayuri; Yokoyama, Masaru; Shioda, Tatsuo; Sato, Hironori; Sakuragi, Jun-Ichi

    2016-11-11

    The dimer initiation site/dimer linkage sequence (DIS/DLS) region of HIV is located on the 5' end of the viral genome and suggested to form complex secondary/tertiary structures. Within this structure, stem-loop 1 (SL1) is believed to be most important and an essential key to dimerization, since the sequence and predicted secondary structure of SL1 are highly stable and conserved among various virus subtypes. In particular, a six-base palindromic sequence is always present at the hairpin loop of SL1 and the formation of kissing-loop structure at this position between the two strands of genomic RNA is suggested to trigger dimerization. Although the higher-order structure model of SL1 is well accepted and perhaps even undoubted lately, there could be stillroom for consideration to depict the functional SL1 structure while in vivo (in virion or cell). In this study, we performed several analyses to identify the nucleotides and/or basepairing within SL1 which are necessary for HIV-1 genome dimerization, encapsidation, recombination and infectivity. We unexpectedly found that some nucleotides that are believed to contribute the formation of the stem do not impact dimerization or infectivity. On the other hand, we found that one G-C basepair involved in stem formation may serve as an alternative dimer interactive site. We also report on our further investigation of the roles of the palindromic sequences on viral replication. Collectively, we aim to assemble a more-comprehensive functional map of SL1 on the HIV-1 viral life cycle. We discovered several possibilities for a novel structure of SL1 in HIV-1 DLS. The newly proposed structure model suggested that the hairpin loop of SL1 appeared larger, and genome dimerization process might consist of more complicated mechanism than previously understood. Further investigations would be still required to fully understand the genome packaging and dimerization of HIV.

  11. Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): effects on size, physical stability and particle matrix structure.

    Science.gov (United States)

    Kovacevic, A; Savic, S; Vuleta, G; Müller, R H; Keck, C M

    2011-03-15

    The two polyhydroxy surfactants polyglycerol 6-distearate (Plurol(®)Stearique WL1009 - (PS)) and caprylyl/capryl glucoside (Plantacare(®) 810 - (PL)) are a class of PEG-free stabilizers, made from renewable resources. They were investigated for stabilization of aqueous solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) dispersions. Production was performed by high pressure homogenization, analysis by photon correlation spectroscopy (PCS), laser diffraction (LD), zeta potential measurements and differential scanning calorimetry (DSC). Particles were made from Cutina CP as solid lipid only (SLN) and its blends with Miglyol 812 (NLC, the blends containing increasing amounts of oil from 20% to 60%). The obtained particle sizes were identical for both surfactants, about 200 nm with polydispersity indices below 0.20 (PCS), and unimodal size distribution (LD). All dispersions with both surfactants were physically stable for 3 months at room temperature, but Plantacare (PL) showing a superior stability. The melting behaviour and crystallinity of bulk lipids/lipid blends were compared to the nanoparticles. Both were lower for the nanoparticles. The crystallinity of dispersions stabilized with PS was higher, the zeta potential decreased with storage time associated with this higher crystallinity, and leading to a few, but negligible larger particles. The lower crystallinity particles stabilized with PL remained unchanged in zeta potential (about -50 mV) and in size. These data show that surfactants have a distinct influence on the particle matrix structure (and related stability and drug loading), to which too little attention was given by now. Despite being from the same surfactant class, the differences on the structure are pronounced. They are attributed to the hydrophobic-lipophilic tail structure with one-point anchoring in the interface (PL), and the loop conformation of PS with two hydrophobic anchor points, i.e. their molecular structure and its

  12. Structural stabilities and electronic properties of fully hydrogenated SiC sheet

    International Nuclear Information System (INIS)

    Wang, Xin-Quan; Wang, Jian-Tao

    2011-01-01

    The intriguing structural and electronic properties of fully hydrogenated SiC honeycomb sheet are studied by means of ab initio calculations. Based on structure optimization and phonon dispersion analysis, we find that both chair-like and boat-like configurations are dynamically stable, and the chair-like conformer is energetically more favored with an energy gain of 0.03 eV per C atom relative to the boat-like one. The chair-like and boat-like conformers are revealed to be nonmagnetic semiconductors with direct band gaps of 3.84 and 4.29 eV, respectively, both larger than 2.55 eV of pristine SiC sheet. The charge density distributions show that the bondings are characterized with covalency for both chair-like and boat-like conformers. -- Highlights: → Structural and electronic properties of fully hydrogenated SiC sheet are studied. → Both chair-like and boat-like configurations are dynamically stable. → While the chair-like conformer is energetically more favored. → The chair-like and boat-like conformers are nonmagnetic semiconductors. → The bondings are characterized with covalency.

  13. Dynamic conformations of nucleophosmin (NPM1 at a key monomer-monomer interface affect oligomer stability and interactions with granzyme B.

    Directory of Open Access Journals (Sweden)

    Wei D Duan-Porter

    Full Text Available Nucleophosmin (NPM1 is an abundant, nucleolar tumor antigen with important roles in cell proliferation and putative contributions to oncogenesis. Wild-type NPM1 forms pentameric oligomers through interactions at the amino-terminal core domain. A truncated form of NPM1 found in some hepatocellular carcinoma tissue formed an unusually stable oligomer and showed increased susceptibility to cleavage by granzyme B. Initiation of translation at the seventh methionine generated a protein (M7-NPM that shared all these properties. We used deuterium exchange mass spectrometry (DXMS to perform a detailed structural analysis of wild-type NPM1 and M7-NPM, and found dynamic conformational shifts or local "unfolding" at a specific monomer-monomer interface which included the β-hairpin "latch." We tested the importance of interactions at the β-hairpin "latch" by replacing a conserved tyrosine in the middle of the β-hairpin loop with glutamic acid, generating Y67E-NPM. Y67E-NPM did not form stable oligomers and further, prevented wild-type NPM1 oligomerization in a dominant-negative fashion, supporting the critical role of the β-hairpin "latch" in monomer-monomer interactions. Also, we show preferential cleavage by granzyme B at one of two available aspartates (either D161 or D122 in M7-NPM and Y67E-NPM, whereas wild-type NPM1 was cleaved at both sites. Thus, we observed a correlation between the propensity to form oligomers and granzyme B cleavage site selection in nucleophosmin proteins, suggesting that a small change at an important monomer-monomer interface can affect conformational shifts and impact protein-protein interactions.

  14. Structures and related properties of helical, disulfide-stabilized peptides

    Energy Technology Data Exchange (ETDEWEB)

    Pagel, Mark D. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    1993-11-01

    The three dimensional structure of several peptides were determined by NMR spectroscopy and distance geometry calculations. Each peptide formed a predictable, rigid structure, consisting of an α-helix, a "scaffold" region which packed along one face of the helix, and two disulfide bridges which covalently connect the helix and scaffold regions. The peptide Apa-M5 was designed to constrain the M5 peptide from MLCK in a helical geometry using the apamin disulfide scaffold. This scaffold constrains the N- terminal end of the helix with two disulfide bridges and a reverse turn. Like the M5 peptide, Apa-M5 was found to bind calmodulin in a Ca2+-dependent 1:1 stoichiometry. However, the dissociation constant of the (Apa-M5)-calmodulin complex, 107 nM, was 100-fold higher than the dissociation constant of the M5-calmodulin complex. This difference was due to a putative steric overlap between the Apa-M5 scaffold and calmodulin. The peptide Apa-Cro was designed to replace the large structural protein matrix of λ Cro with the apamin disulfide scaffold. However, Apa-Cro did not bind the consensus DNA operator half-site of λ Cro, probably due to a steric overlap between the Apa-Cro disulfide framework and the DNA. The amino acid sequence of the scaffold-disulfide bridge arrangement of the peptide Max was derived from the core sequence of scyllatoxin, which contains an α-helix constrained at the C-terminal end by two disulfide bridges and a two-stranded βsheet scaffold. Max was shown to fold with >84% yield to form a predictable, stable structure that is similar to scyllatoxin. The folding and stability properties of Max make this scaffold and disulfide bridge arrangement an ideal candidate for the development of hybrid sequence peptides. The dynamics of a fraying C-terminal end of the helix of the peptide Apa-AlaN was determined by analysis of 15N NMR relaxation properties.

  15. Structure and stability of small H clusters on graphene

    DEFF Research Database (Denmark)

    Sljivancanin, Zeljko; Andersen, Mie; Hammer, Bjørk

    2011-01-01

    The structure and stability of small hydrogen clusters adsorbed on graphene is studied by means of density functional theory (DFT) calculations. Clusters containing up to six H atoms are investigated systematically, with the clusters having either all H atoms on one side of the graphene sheet (cis......-clusters) or having the H atoms on both sides in an alternating manner (trans-clusters). The most stable cis-clusters found have H atoms in ortho- and para-positions with respect to each other (two H’s on neighboring or diagonally opposite carbon positions within one carbon hexagon), while the most stable trans......-clusters found have H atoms in ortho-trans-positions with respect to each other (two H’s on neighboring carbon positions, but on opposite sides of the graphene). Very stable trans-clusters with 13–22 H atoms were identified by optimizing the number of H atoms in ortho-trans-positions and thereby the number...

  16. STABILITY AND DYNAMICS OF SPATIO-TEMPORAL STRUCTURES

    Energy Technology Data Exchange (ETDEWEB)

    Hermann Riecke

    2005-10-21

    This document constitutes the final report for the grant. It provides a complete list of publications and presentations that arose from the project as well as a brief description of the highlights of the research results. The research funded by this grant has provided insights into the spontaneous formation of structures of increasing complexity in systems driven far from thermodynamic equilibrium. A classic example of such a system is thermally driven convection in a horizontal fluid layer. Highlights of the research are: (1) explanation of the localized traveling wave pulses observed in binary-mixture convection, (2) explanation of the localized waves in electroconvection, (3) introduction of a new diagnostics for spatially and temporally chaotic states, which is based on the statistics of defect trajectories, (4) prediction of complex states in thermally driven convection in rotating systems. Additional contributions provided insight into the localization mechanism for oscillons, the prediction of a new localization mechanism for traveling waves based on a resonant periodic forcing, and an analysis of the stability of quasi-periodic patterns.

  17. Structure, spectra and stability of solid bismuth carbonates

    International Nuclear Information System (INIS)

    Taylor, Peter; Sunder, S.; Lopata, V.J.

    1984-01-01

    A previously unreported basic bismuth carbonate, (BiO)sub(4)(OH)sub(2)COsub(3), has been identified as an intermediate product in the interconversion of α-Bisub(2)Osub(3) and synthetic bismutite, (BiO)sub(2)COsub(3), in aqueous carbonate solutions. It has a narrow stability field between COsub(2) partial pressures of 10sup(-5.5+-1.0) Pa, in the presence of dilute aqueous solution at 25 degrees C. Gibbs energies of formation, calculated from these partial pressures, are Δsub(f)Gsup(0)((BiO)sub(4)(OH)sub(2)COsub(3),s,298.15 K)-1678 +- 9 kJ molsup(-1) and Δsub(f)Gsup(0)((BiO)sub(2)COsub(3),s,298.15 K)=-945 +- 7 kJ molsup(-1). The two carbonates have been compared by thermogravimetric analysis, X-ray powder diffractometry, and infrared and Raman spectroscopy. The unit cell of (BiO)sub(4)(OH)sub(2)COsub(3) is dimensionally orthorhombic, with a=10.772(1), b=5.4898(5), c=14.757(1)angstrom,Z=4, but its true symmetry is probably triclinic. A structural model for (BiO)sub(4)(OH)sub(2)COsub(3), and two modified models for (BiO)sub(2)COsub(3), are proposed. The possible natural occurrence of (BiO)sub(4)(OH)sub(2)COsub(3) is discussed

  18. 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.

  19. Workers’ Conformism

    Directory of Open Access Journals (Sweden)

    Nikolay Ivantchev

    2013-10-01

    Full Text Available Conformism was studied among 46 workers with different kinds of occupations by means of two modified scales measuring conformity by Santor, Messervey, and Kusumakar (2000 – scale for perceived peer pressure and scale for conformism in antisocial situations. The hypothesis of the study that workers’ conformism is expressed in a medium degree was confirmed partly. More than a half of the workers conform in a medium degree for taking risk, and for the use of alcohol and drugs, and for sexual relationships. More than a half of the respondents conform in a small degree for anti-social activities (like a theft. The workers were more inclined to conform for risk taking (10.9%, then – for the use of alcohol, drugs and for sexual relationships (8.7%, and in the lowest degree – for anti-social activities (6.5%. The workers who were inclined for the use of alcohol and drugs tended also to conform for anti-social activities.

  20. Bicyclo[3.2.0]heptane as a Core Structure for Conformational Locking of 1,3-Bis-Pharmacophores, Exemplified by GABA

    DEFF Research Database (Denmark)

    Vorberg, Raffael; Trapp, Nils; Carreira, Erick M

    2017-01-01

    The synthesis and X-ray crystal structures of syn and anti 4-N-Boc-aminobicyclo[3.2.0]heptane-1-carboxylic acids are described. The placement of the N-Boc-amino groups in the two stereoisomers in either pseudo-equatorial or pseudo-axial positions renders the molecules conformationally locked......, with N-Boc-protected γ-aminobutyric acid (GABA) embedded within the bicyclic core. Despite the different conformations of the urethane and distinct crystal packing, the bicyclic core units of the two stereoisomers adopt virtually identical structures. They correspond to in silico models of the parent...

  1. Accuracy Enhanced Stability and Structure Preserving Model Reduction Technique for Dynamical Systems with Second Order Structure

    DEFF Research Database (Denmark)

    Tahavori, Maryamsadat; Shaker, Hamid Reza

    A method for model reduction of dynamical systems with the second order structure is proposed in this paper. The proposed technique preserves the second order structure of the system, and also preserves the stability of the original systems. The method uses the controllability and observability...... gramians within the time interval to build the appropriate Petrov-Galerkin projection for dynamical systems within the time interval of interest. The bound on approximation error is also derived. The numerical results are compared with the counterparts from other techniques. The results confirm...

  2. Structure and conformational dynamics of the domain 5 RNA hairpin of a bacterial group II intron revealed by solution nuclear magnetic resonance and molecular dynamics simulations.

    Science.gov (United States)

    Pechlaner, Maria; Sigel, Roland K O; van Gunsteren, Wilfred F; Dolenc, Jožica

    2013-10-08

    Nuclear magnetic resonance (NMR) nuclear Overhauser enhancement (NOE) data obtained for a 35-nucleotide RNA segment of a bacterial group II intron indicate a helical hairpin structure in which three parts, a terminal pentaloop, a bulge, and a G-A mismatch, display no Watson-Crick base pairing. The 668 NOE upper distance bounds for atom pairs are insufficient to uniquely determine the conformation of these segments. Therefore, molecular dynamics simulations including time-averaged distance restraints have been used to obtain a conformational ensemble compatible with the observed NMR data. The ensemble shows alternating hydrogen bonding patterns for the mentioned segments. In particular, in the pentaloop and in the bulge, the hydrogen bonding networks correspond to distinct conformational clusters that could not be captured by using conventional single-structure refinement techniques. This implies that, to obtain a realistic picture of the conformational ensemble of such flexible biomolecules, it is necessary to properly account for the conformational variability in the structure refinement of RNA fragments.

  3. The changing face of glucagon fibrillation: Structural polymorphism and conformational imprinting

    DEFF Research Database (Denmark)

    Pedersen, J.S.; Dikov, D.; Flink, J.L.

    2006-01-01

    concentration) appear less thermostable than those formed under more challenging conditions (high temperatures, low glucagon or low salt concentrations). Properties of preformed fibrils used for seeding are inherited in a prion-like manner. Thus, we conclude that the structure of fibrils formed by glucagon...

  4. Structural domains and conformational changes in nuclear chromatin: a quantitative thermodynamic approach by differential scanning calorimetry.

    Science.gov (United States)

    Balbi, C; Abelmoschi, M L; Gogioso, L; Parodi, S; Barboro, P; Cavazza, B; Patrone, E

    1989-04-18

    A good deal of information on the thermodynamic properties of chromatin was derived in the last few years from optical melting experiments. The structural domains of the polynucleosomal chain, the linker, and the core particle denature as independent units. The differential scanning calorimetry profile of isolated chromatin is made up of three endotherms, at approximately 74, 90, and 107 degrees C, having an almost Gaussian shape. Previous work on this matter, however, was mainly concerned with the dependence of the transition enthalpy on external parameters, such as the ionic strength, or with the melting of nuclei from different sources. In this paper we report the structural assignment of the transitions of rat liver nuclei, observed at 58, 66, 75, 92, and 107 degrees C. They are representative of the quiescent state of the cell. The strategy adopted in this work builds on the method developed for the investigation of complex biological macromolecules. The heat absorption profile of the nucleus was related to the denaturation of isolated nuclear components; electron microscopy and electrophoretic techniques were used for their morphological and molecular characterization. The digestion of chromatin by endogenous nuclease mimics perfectly the decondensation of the higher order structure and represented the source of several misinterpretations. This point was carefully examined in order to define unambiguously the thermal profile of native nuclei. The low-temperature transitions, centered around 58 and 66 degrees C, arise from the melting of scaffolding structures and of the proteins associated with heterogeneous nuclear RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Conformational, structural, vibrational, electronic and quantum chemical investigations of cis-2-methoxycinnamic acid

    Science.gov (United States)

    Arjunan, V.; Anitha, R.; Marchewka, M. K.; Mohan, S.; Yang, Haifeng

    2015-01-01

    The Fourier transform infrared (FTIR) and FT-Raman spectra of cis-2-methoxycinnamic acid have been measured in the range 4000-400 and 4000-100 cm-1, respectively. Complete vibrational assignment and analysis of the fundamental modes of the compound were carried out using the observed FTIR and FT-Raman data. The geometry was optimised without any symmetry constrains using the DFT/B3LYP method utilising 6-311++G∗∗ and cc-pVTZ basis sets. The thermodynamic stability and chemical reactivity descriptors of the molecule have been determined. The exact environment of C and H of the molecule has been analysed by NMR spectroscopies through 1H and 13C NMR chemical shifts of the molecule. The energies of the frontier molecular orbitals have also been determined. Complete NBO analysis was also carried out to find out the intramolecular electronic interactions and their stabilisation energy. The vibrational frequencies which were determined experimentally are compared with those obtained theoretically from density functional theory (DFT) gradient calculations employing the B3LYP/6-311++G∗∗ and cc-pVTZ methods.

  6. Role and structural mechanism of WASP-triggered conformational changes in branched actin filament nucleation by Arp2/3 complex.

    Science.gov (United States)

    Rodnick-Smith, Max; Luan, Qing; Liu, Su-Ling; Nolen, Brad J

    2016-07-05

    The Arp2/3 (Actin-related proteins 2/3) complex is activated by WASP (Wiskott-Aldrich syndrome protein) family proteins to nucleate branched actin filaments that are important for cellular motility. WASP recruits actin monomers to the complex and stimulates movement of Arp2 and Arp3 into a "short-pitch" conformation that mimics the arrangement of actin subunits within filaments. The relative contribution of these functions in Arp2/3 complex activation and the mechanism by which WASP stimulates the conformational change have been unknown. We purified budding yeast Arp2/3 complex held in or near the short-pitch conformation by an engineered covalent cross-link to determine if the WASP-induced conformational change is sufficient for activity. Remarkably, cross-linked Arp2/3 complex bypasses the need for WASP in activation and is more active than WASP-activated Arp2/3 complex. These data indicate that stimulation of the short-pitch conformation is the critical activating function of WASP and that monomer delivery is not a fundamental requirement for nucleation but is a specific requirement for WASP-mediated activation. During activation, WASP limits nucleation rates by releasing slowly from nascent branches. The cross-linked complex is inhibited by WASP's CA region, even though CA potently stimulates cross-linking, suggesting that slow WASP detachment masks the activating potential of the short-pitch conformational switch. We use structure-based mutations and WASP-Arp fusion chimeras to determine how WASP stimulates movement toward the short-pitch conformation. Our data indicate that WASP displaces the autoinhibitory Arp3 C-terminal tail from a hydrophobic groove at Arp3's barbed end to destabilize the inactive state, providing a mechanism by which WASP stimulates the short-pitch conformation and activates Arp2/3 complex.

  7. Conformal superalgebras via tractor calculus

    Science.gov (United States)

    Lischewski, Andree

    2015-01-01

    We use the manifestly conformally invariant description of a Lorentzian conformal structure in terms of a parabolic Cartan geometry in order to introduce a superalgebra structure on the space of twistor spinors and normal conformal vector fields formulated in purely algebraic terms on parallel sections in tractor bundles. Via a fixed metric in the conformal class, one reproduces a conformal superalgebra structure that has been considered in the literature before. The tractor approach, however, makes clear that the failure of this object to be a Lie superalgebra in certain cases is due to purely algebraic identities on the spinor module and to special properties of the conformal holonomy representation. Moreover, it naturally generalizes to higher signatures. This yields new formulas for constructing new twistor spinors and higher order normal conformal Killing forms out of existing ones, generalizing the well-known spinorial Lie derivative. Moreover, we derive restrictions on the possible dimension of the space of twistor spinors in any metric signature.

  8. Conformational analysis and electronic structure of chiral carbon and carbon nitride nanotubes

    Directory of Open Access Journals (Sweden)

    Cristiano Geraldo de Faria

    2011-12-01

    Full Text Available Geometry and electronic structure of chiral carbon and carbon nitride (CNx nanotubes were investigated through quantum chemical methods. Finite nanotubes with diameters ranging from 5 to 10 Å and containing up to 500 atoms were considered. CNx structures were built through random substitution of carbon atoms by nitrogen. The molecules were fully optimized by semi-empirical quantum chemical method (PM3. Our results show that the energy associated with nitrogen incorporation depends strongly upon the tube helicity and diameter. The doping of nanotubes with nitrogen contributes to reduce the stress caused by the small diameter of the studied systems. Density of States (DOS results for pure carbon and CNx nanostructures, obtained through DFT and Hartree-Fock calculations, were analyzed. The introduction of nitrogen in the tube produce states in the gap region which characterizes the metallic behavior, as expected for these systems after N-doping.

  9. Spatial structure of neuropeptide allatostatin-4

    International Nuclear Information System (INIS)

    Veliyeva, L.I.; Aliyev, E.Z.

    2011-01-01

    By method of conformational analysis there was determined the spatial structure of neuropeptide allatostatin-4 belonging to allatostatins family. On the basic of value of intramolecular conformational energy calculation was conducted quantitative assessment of the stability of molecule's possible conformational status in dipolar medium terms

  10. Conformal structure in the spectrum of an altered quantum Ising chain

    International Nuclear Information System (INIS)

    Henkel, M.; Patkos, A.

    1986-07-01

    The Ising model with an infinite line of defects is mapped onto a strip with two defect lines. The Hamiltonian spectrum is studied at the bulk critical point. Its exact diagonal form is found for an infinite number of sites. The spectrum of physical excitations contains an infinite number of primary fields, while the leading ground state energy correction is independent of the defect strength. A novel algebraic structure interpolating between those belonging to periodic and free boundary conditions is signalled. (orig.)

  11. The Staphylococcus aureus extracellular adherence protein (Eap) adopts an elongated but structured conformation in solution

    OpenAIRE

    Hammel, Michal; Němeček, Daniel; Keightley, J. Andrew; Thomas, George J.; Geisbrecht, Brian V.

    2007-01-01

    The extracellular adherence protein (Eap) of Staphylococcus aureus participates in a wide range of protein–protein interactions that facilitate the initiation and dissemination of Staphylococcal disease. In this report, we describe the use of a multidisciplinary approach to characterize the solution structure of full-length Eap. In contrast to previous reports suggesting that a six-domain isoform of Eap undergoes multimerization, sedimentation equilibrium analytical ultracentrifugation data r...

  12. Modeling Insight into Battery Electrolyte Electrochemical Stability and Interfacial Structure.

    Science.gov (United States)

    Borodin, Oleg; Ren, Xiaoming; Vatamanu, Jenel; von Wald Cresce, Arthur; Knap, Jaroslaw; Xu, Kang

    2017-12-19

    Electroactive interfaces distinguish electrochemistry from chemistry and enable electrochemical energy devices like batteries, fuel cells, and electric double layer capacitors. In batteries, electrolytes should be either thermodynamically stable at the electrode interfaces or kinetically stable by forming an electronically insulating but ionically conducting interphase. In addition to a traditional optimization of electrolytes by adding cosolvents and sacrificial additives to preferentially reduce or oxidize at the electrode surfaces, knowledge of the local electrolyte composition and structure within the double layer as a function of voltage constitutes the basis of manipulating an interphase and expanding the operating windows of electrochemical devices. In this work, we focus on how the molecular-scale insight into the solvent and ion partitioning in the electrolyte double layer as a function of applied potential could predict changes in electrolyte stability and its initial oxidation and reduction reactions. In molecular dynamics (MD) simulations, highly concentrated lithium aqueous and nonaqueous electrolytes were found to exclude the solvent molecules from directly interacting with the positive electrode surface, which provides an additional mechanism for extending the electrolyte oxidation stability in addition to the well-established simple elimination of "free" solvent at high salt concentrations. We demonstrate that depending on their chemical structures, the anions could be designed to preferentially adsorb or desorb from the positive electrode with increasing electrode potential. This provides additional leverage to dictate the order of anion oxidation and to effectively select a sacrificial anion for decomposition. The opposite electrosorption behaviors of bis(trifluoromethane)sulfonimide (TFSI) and trifluoromethanesulfonate (OTF) as predicted by MD simulation in highly concentrated aqueous electrolytes were confirmed by surface enhanced infrared

  13. Theoretical study of γ-aminobutyric acid conformers: Intramolecular interactions and ionization energies

    Science.gov (United States)

    Wang, Ke-Dong; Wang, Mei-Ting; Meng, Ju

    2014-10-01

    Allowing for all combinations of internal single-bond rotamers, 1,296 unique trial structures of γ-Aminobutyric acid (GABA) are obtained. All of these structures are optimized at the M06-2X level of theory and a total of 68 local minimal conformers are found. The nine low-lying conformers are used for further studies. According to the calculated relative Gibbs free energies at M06-2X level of theory, we find that the dispersion is important for the relative energy of GABA. The intramolecular hydrogen bonds and hyperconjugative interaction and their effects on the conformational stability are studied. The results show that both of them have great influence on the conformers. The vertical ionization energies (VIE) are calculated and match the experimental data well. The results show that the neutral GABA in the gas phase is a multi-conformer system and at least four conformations exist.

  14. Conformational analysis, spectroscopic, structure-activity relations and quantum chemical simulation studies of 4-(trifluoromethyl)benzylamine

    Science.gov (United States)

    Arjunan, V.; Devi, L.; Mohan, S.

    2018-05-01

    The FT-IR and FT-Raman spectra of 4-trifluoromethylbenzylamine (TFMBA) have been recorded in the range 4000-450 and 4000-100 cm-1 respectively. The conformational analysis of the compound has been carried out to attain stable geometry of the compound. The complete vibrational assignment and analysis of the fundamental modes of the compound are carried out using the experimental FTIR and FT-Raman data and quantum chemical studies. The experimental vibrational frequencies are compared with the wavenumbers obtained theoretically from the B3LYP gradient calculations employing the standard high level 6-311++G** and cc-pVTZ basis sets for the optimised geometry of the compound. The structural parameters, thermodynamic properties and vibrational frequencies of the normal modes obtained from the B3LYP methods are in good agreement with the experimental data. The 1H (400 MHz; CDCl3) and 13C (100 MHz; CDCl3) nuclear magnetic resonance (NMR) spectra were also recorded. The electronic properties, highest occupied molecular orbital and lowest unoccupied molecular orbital energies are measured by DFT approach. The charges of the atoms by natural bond orbital (NBO) analysis are determined by B3LYP/cc-pVTZ method. The structure-chemical reactivity relations of the compound are determined through chemical potential, global hardness, global softness, electronegativity, electrophilicity and local reactivity descriptors by conceptual DFT methods.

  15. Structures of LeuT in bicelles define conformation and substrate binding in a membrane-like context

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui; Elferich, Johannes; Gouaux, Eric (Oregon HSU)

    2012-02-13

    Neurotransmitter sodium symporters (NSSs) catalyze the uptake of neurotransmitters into cells, terminating neurotransmission at chemical synapses. Consistent with the role of NSSs in the central nervous system, they are implicated in multiple diseases and disorders. LeuT, from Aquifex aeolicus, is a prokaryotic ortholog of the NSS family and has contributed to our understanding of the structure, mechanism and pharmacology of NSSs. At present, however, the functional state of LeuT in crystals grown in the presence of n-octyl-{beta}-D-glucopyranoside ({beta}-OG) and the number of substrate binding sites are controversial issues. Here we present crystal structures of LeuT grown in DMPC-CHAPSO bicelles and demonstrate that the conformations of LeuT-substrate complexes in lipid bicelles and in {beta}-OG detergent micelles are nearly identical. Furthermore, using crystals grown in bicelles and the substrate leucine or the substrate analog selenomethionine, we find only a single substrate molecule in the primary binding site.

  16. Counterion Association and Structural Conformation Change of Charged PAMAM Dendrimer in Aqueous Solutions Revealed by Small Angle Neutron Scattering

    International Nuclear Information System (INIS)

    Chen, Wei-Ren

    2009-01-01

    Our previous study of the structure change of poly(amidoamine) starburst dendrimers (PAMAM) dendrimer of generation 5 (G5) have demonstrated that although the overall molecular size is practically unaffected by increasing DCl concentration, a configurational transformation, from a diffusive density profile to a more uniform density distribution, is clearly observed. In the current paper, the focus is placed on understanding the effect of counterion identity on the inter-molecular structure and the conformational properties by studying the effect due to DBr using small angle neutron scattering (SANS) and integral equation theory. While the overall molecular size is found to be essentially unaffected by the change in the pD of solutions, it is surprising that the intra-molecular configurational transformation is not observed when DBr is used. The overall effective charge of a dendrimer is nearly the same for 1, the effect of counterion identity becomes significant, the effective charge carried by a charged G5 PAPAM protonated by DBr becomes smaller than that of solutions with DCl. As a consequence, a counterion identity dependence of counterion association is revealed: Under the same level of molecular protonation, the specific counterion association, which is defined as the ratio of bound chloride anions to positively charged amines per molecule, is larger for the G5 PAMAM dendrimer charged by DBr than the one by DCl.

  17. Structural fluctuations and orientational glass of levoglucosan--High stability against ordering and absence of structural glass.

    Science.gov (United States)

    Tombari, Elpidio; Johari, G P

    2015-03-14

    To investigate whether a non-exponential relaxation always indicates 2-4 nm-size regions of dynamic heterogeneity, we studied the kinetic freezing and unfreezing of structural fluctuations involving the rotational modes in orientationally disordered crystal (ODIC) of levoglucosan by calorimetry. The heat capacity, Cp, of levoglucosan measured over the 203 K-463 K range shows that its low-temperature, orientationally ordered crystal (ORC) transforms to ODIC phase on heating, which then melts to a low viscosity liquid. On cooling, the melt transforms to the ODIC which then does not transform to the ORC. Instead, the ODIC supercools. Fluctuations resulting from hindered (random) rotations of levoglucosan molecules confined to the lattice sites and from their conformational changes become progressively slower on cooling and an orientational glass (O-G) forms showing the sigmoid shape decrease in Cp characteristic of structural arrest like that of a glass. On heating the O-G state, rotational fluctuations begin to contribute to Cp at To-g of 247.8 K and there is an overshoot in Cp and thermal hysteresis (characteristic of physical ageing) in the temperature range of 230-260 K. The non-exponential relaxation parameter, β(cal), determined by fitting the Cp data to a non-exponential, nonlinear model for relaxation of a glass is 0.60, which is similar to β(cal) found for polymers, molecular liquids, and metal-alloy melts in which Brownian diffusion occurs. Such β(cal) glass formation, but its value of 0.60 for ODIC levoglucosan, in which Brownian diffusion does not occur, would not indicate such domains. Despite the lack of Brownian diffusion, we discuss these findings in the potential energy landscape paradigm. Levoglucosan melt, which is believed to vitrify and to stabilize a protein's disordered structure, did not supercool even at 200 K/min cooling rate. The findings have consequences for reports on the dielectric relaxation studies that indicated that levoglucosan

  18. ON THE STABILIZATION OF THE LINEAR HYBRID SYSTEM STRUCTURE

    Directory of Open Access Journals (Sweden)

    Kirillov

    2014-11-01

    Full Text Available The linear control hybrid system, consisting of a fi- nite set of subsystems (modes having different dimensions, is considered. The moments of reset time are determined by some complementary function – evolutionary time. This function satisfies the special complementary ordinary differential equation. The mode stabilization problem is solved for some class of piecewise linear controls. The method of stabilization relies on the set of invariant planes, the existence of which is due to the special form of the hybrid system.

  19. THE IMPACT OF CAPITAL STRUCTURE ON THE ENTERPRISE FINANCIAL STABILITY

    Directory of Open Access Journals (Sweden)

    A. V. Ivanyshcheva

    2009-06-01

    Full Text Available Functioning of production enterprises in the conditions of continuous change of market environment require a special attention of management system to providing their activities. The enterprise financial stability management is one of integral parts of the management system. The increased or insufficient financial stability adversely affects the enterprise competition ability that leads to decreasing the profitability and worsening the financial results of its activities.

  20. Using mass spectrometry and small molecule reagents to detect distinctive structural features of different prion conformations (strains)

    Science.gov (United States)

    A prion (PrPSc) is a conformer of a normal cellular prion protein (PrPC). Although they are isosequential, PrPSc is an infectious protein able to convert PrPC into the prion conformation and thereby propagate an infection. PrPC is monomeric while PrPSc is a multimer. PrPSc can adopt more than one co...

  1. Molecular structure and conformation of two acyclic polythioethers: Implications for the design of heavy metal chelators

    Energy Technology Data Exchange (ETDEWEB)

    Desper, J.M.; Powell, D.R.; Gellman, S.H. (Univ. of Wisconsin, Madison (USA))

    1990-05-23

    The crystal structures of the 1,9-bis(p-tolyl)-2,5,8-trithianonane (1) and 1,12-bis(p-tolyl)-2,5,8,11-tetrathiadodecane (2) are reported. Previous studies of macrocyclic polythioethers have revealed a pronounced tendency for backbone CS-CC bonds to adopt gauche torsion angles. The same tendency is observed in the homologous acyclic polythioethers 1 and 2, demonstrating that the gauche preference is not simply the result of a macrocyclic constraint. Because of this gauche preference of CS-CC torsion units and the well-established anti preference of SC-CS torsion units, polythioethers constructed from ethylene sulfide subunits are generally far from preorganized for metal ion chelation.

  2. A new look into conformational, vibrational and electronic structure analysis of 3,4-dimethoxybenzonitrile.

    Science.gov (United States)

    Arjunan, V; Devi, L; Remya, P; Mohan, S

    2013-09-01

    The FTIR and FT-Raman spectra of 3,4-dimethoxybenzonitrile (34DMBN) have been analysed. Quantum chemical studies were performed with B3LYP method using 6-311++G(d,p), 6-31G(d,p) and cc-pVTZ basis sets. The electron donating effect of -OCH3 and electron withdrawing effect of -C≡N groups on the ring parameters were thoroughly analysed. The structural parameters, energies, thermodynamic properties, vibrational frequencies and the NBO charges of 34DMBN were determined. The (1)H and (13)C chemical shifts with respect to TMS were investigated and also calculated theoretically using the gauge independent atomic orbital method and compared with the experimental data. The delocalisation energy of different types of bonding interactions was investigated. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Conformal Infinity

    Directory of Open Access Journals (Sweden)

    Frauendiener Jörg

    2000-08-01

    Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, ``conformal infinity'' is related with almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved out of physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation and how it lends itself very naturally to solve radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  4. Conformal Infinity.

    Science.gov (United States)

    Frauendiener, Jörg

    2004-01-01

    The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  5. Conformal Infinity

    Directory of Open Access Journals (Sweden)

    Frauendiener Jörg

    2004-01-01

    Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, 'conformal infinity' is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  6. General Conformity

    Science.gov (United States)

    The General Conformity requirements ensure that the actions taken by federal agencies in nonattainment and maintenance areas do not interfere with a state’s plans to meet national standards for air quality.

  7. The influence of the side-chain sequence on the structure-activity correlations of immunomodulatory branched polypeptides. Synthesis and conformational analysis of new model polypeptides.

    Science.gov (United States)

    Mezö, G; Hudecz, F; Kajtár, J; Szókán, G; Szekerke, M

    1989-10-01

    New branched polypeptides were synthesized for a detailed study of the influence of the side-chain structure on the conformation and biological properties. The first subset of polypeptides were prepared by coupling of tetrapeptides to poly[L-Lys]. These polymers contain either DL-Ala3-X [poly[Lys-(X-DL-Ala3)n

  8. Crystal Structure, Conformational Analysis, and Charge Density Distribution for Eng-Epifisetinidol: An Explanation for Regiospecific Aromatic Substitution of 5-Deoxyflavan

    Science.gov (United States)

    Fred L. Tobiason; Frank R. Fronczek; Jan P. Steynberg; Elizabeth C. Steynberg; Richard W. Hemingway; Wayne L. Mattice

    1993-01-01

    Molecular modeling and molecular orbital analyses of ent-epifisetinidol gave &ood predictions of the approximate "reverse half-chair" conformation found for the crystal structure. MNDO and AM1 analyses of HOMO electron densities provided an explanation for the stereospecific electrophilic aromatic substitution at C(6) in 5-deoxy-flavans...

  9. Analytic structure of the n=7 scattering amplitude in N=4 SYM theory in multi-Regge kinematics. Conformal Regge cut contribution

    International Nuclear Information System (INIS)

    Bartels, Jochen; Kormilitzin, Andrey; Oxford Univ.; Lipatov, Lev N.; Oxford Univ.; St. Petersburg State Univ.

    2014-11-01

    In this second part of our investigation of the analytic structure of the 2→5 scattering amplitude in the planar limit of N=4 SYM in multi-Regge kinematics we compute, in all kinematic regions, the Regge cut contributions in leading order. The results are infrared finite and conformally invariant.

  10. Conformal Infinity

    OpenAIRE

    Frauendiener, J?rg

    2000-01-01

    The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, 'conformal infinity' is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory...

  11. Synthesis, Structure, Stability and Redispersion of Gold-based Nanoparticles

    Science.gov (United States)

    Tiruvalam, Ram Chandra

    ' particles with Pd-shell/Au-core and Au-shell/Pd-core morphologies, have been prepared and immobilized on both activated carbon and TiO2 supports. These have subsequently been compared as catalysts for the direct production of H2O2 and for benzyl alcohol oxidation in an attempt to elucidate the optimum particle morphology/support combination for both these reactions. Aberration corrected analytical electron microscopy has been used extensively to characterize these sol-immobilized materials. In particular, the STEM -HAADF technique has provided invaluable new (and often unexpected) information on the atomic structure, elemental distribution within particles, and compositional variations between particles for these controlled catalyst preparations. In addition, we have been able to compare their differing thermal stability and sintering behaviors, and to demonstrate that they have quite varying wetting interactions with activated carbon and TiO2 supports. Over the course of their lifetime, many supported metal catalysts exposed to elevated temperatures tend to de-activate by nanoparticle sintering, which decreases the overall exposed metal surface area and the number of active sites available for catalysis. It is sometimes desirable to devise chemical re-dispersion treatments whereby the mean size of the particles is reduced and the catalytic activity regenerated. In this work, the possibility of re-dispersing gold nanoparticles by a simple low temperature methyl iodide (CH3 I) treatment has been investigated. A variety of characterization techniques, including EXAFS, XRD, XPS, UV-DRS and STEM-HAADF imaging has been applied to samples before and after CH3 I treatment, in an attempt to determine the efficacy of the re-dispersion method. It is shown that re-dispersion of Au nanoparticles on activated carbon, graphite, Al2 O3 and TiO2 substrates is possible to varying degrees. A complete re-dispersion of `bulk' gold nanoparticles down to the atomic scale has been achieved on

  12. Relationship of the vibrational frequency of the nuclear pair Mo-Cl with it electronegativity, force constant and bond length in the structural conformation of molybden dichloride

    International Nuclear Information System (INIS)

    Rodriguez S, A.; Martinez Q, E.

    1990-08-01

    The structural elucidation of the cluster hexamerico (MO 6 C1 8 ) 4+ , it has been characterized for but of twenty-five years like a conformation octahedrica of simple metallic connections. However, the determination has not been attempted of some physical characteristics of this conformation by means of measures espectroscopicas. We present the electronegatividad measures now, constant of force and it distances of connection of the nuclear couple Mo-Cl, using only their frequency vibracional taken directly of the infrared spectra. (Author)

  13. Constitutional Isomers of Dendrimer-like Star Polymers: Design, Synthesis and Conformational and Structural Properties; TOPICAL

    International Nuclear Information System (INIS)

    Pople, John A.

    2001-01-01

    The design, synthesis and solution properties of six constitutional isomers of dendrimer-like star polymers is described. Each of the polymers have comparable molecular weights ((approx) 80,000 g/mol), narrow polydispersities ( and lt; 1.19) and an identical number of branching junctures (45) and surface hydroxyl functionalities (48). The only difference in the six isomers is the placement of the branching junctures. The polymers are constructed from high molecular weight poly(e-caprolactone) with branching junctures derived from 2,2'-bis(hydroxylmethyl) propionic acid (bis-MPA) emanating from a central core. The use of various generations of dendritic initiators and dendrons coupled with the ring opening polymerization of e-caprolactones allowed a modular approach to the dendrimer-like star polymer isomers. The most pronounced effects on the physical properties/morphology and hydrodynamic volume was for those polymers in which the branching was distributed throughout the sample in a dendrimer-like fashion. The versatility of this approach has provided the possibility of understanding the relationship between architecture and physical properties. Dynamic light scattering and small angle X-ray scattering techniques were used to determine the hydrodynamic radius Rh and radius of gyration Rg respectively. The relationship between Rg and molecular weight was indicative of a compact star-like structure, and did not show advanced bias towards either the dense core or dense shell models. The radial density distribution of the isomers was therefore modeled according to a many arm star polymer, and good agreement was found with experimental measures of Rh/Rg

  14. Synthesis, structure combined with conformational analysis, biological activities and docking studies of bis benzylidene cyclohexanone derivatives

    Directory of Open Access Journals (Sweden)

    Gehad Lotfy

    2017-07-01

    Full Text Available We report the synthesis and biological evaluation of bis benzylidne cyclohexanone derivatives 2,6-di(4-fluorobenzylidenecyclohexanone 3a and (2E,6E‐2,6‐bis({[4‐(trifluoromethylphenyl]methylidene}cyclohexanone 3b. Compound 3b crystallized in the monoclinic space group P21/n with unit cell parameters a = 29.3527(12 Å, b = 8.3147(3 Å, c = 32.7452(14 Å, β = 112.437(2°, and V = 7386.8(5 Å3, Z = 16, and Rint = 0.072 at T = 100 K. The asymmetric unit contains four independent molecules, each of which has slight differences in the bond lengths and angles. One non-classical C11D–H11F⋯F3A hydrogen bond connects the molecules. Density functional theory was used to optimize the structures and calculate the natural charges, dipole moments, frontier molecular orbitals, and NMR and UV–Vis spectroscopic properties, which are discussed and compared with the experimental data. The synthetic derivatives were evaluated for α-glucosidase inhibitory activity, and we found that compound 3a (IC50 = 96.3 ± 0.51 μM is a potent α-glucosidase inhibitor, showing superior activity to the standard drug acarbose (IC50 = 841 ± 1.73 μM. Compound 3b (IC50 = 7.92 ± 1.3 μg/mL was found to be a potent antileishmanial compound, especially compared to the antileishmanial drugs pentamidine (IC50 = 5.09 ± 0.04 μM and amphotericine B (IC50 = 0.29 ± 0.05 μg/mL. In addition, 3a and 3b have cytotoxic effects against PC3 (prostate cancer, HeLa (cervical cancer, and MCF-3 (breast cancer cell lines. Docking study for compounds activity was performed with Openeye software in order to understanding their pose of interaction in the target receptors.

  15. Characterization of the Elusive Conformers of Glycine from State-of-the-Art Structural, Thermodynamic, and Spectroscopic Computations: Theory Complements Experiment.

    Science.gov (United States)

    Barone, Vincenzo; Biczysko, Malgorzata; Bloino, Julien; Puzzarini, Cristina

    2013-03-12

    A state-of-the-art computational strategy for the evaluation of accurate molecular structures as well as thermodynamic and spectroscopic properties along with the direct simulation of infrared (IR) and Raman spectra is established, validated (on the basis of the experimental data available for the Ip glycine conformer) and then used to provide a reliable and accurate characterization of the elusive IVn/gtt and IIIp/tct glycine conformers. The integrated theoretical model proposed is based on accurate post-Hartree-Fock computations (involving composite schemes) of energies, structures, properties, and harmonic force fields coupled to DFT corrections for the proper inclusion of vibrational effects at an anharmonic level (as provided by general second-order perturbative approach). It is shown that the approach presented here allows the evaluation of structural, thermodynamic, and spectroscopic properties with an overall accuracy of about, or better than, 0.001 Å, 20 MHz, 1 kJ·mol(-1), and 10 cm(-1) for bond distances, rotational constants, conformational enthalpies, and vibrational frequencies, respectively. The high accuracy of the computational results allows one to support and complement experimental studies, thus providing (i) an unequivocal identification of several conformers concomitantly present in the experimental mixture and (ii) data not available or difficult to experimentally derive.

  16. Numerical estimation of structure constants in the three-dimensional Ising conformal field theory through Markov chain uv sampler

    Science.gov (United States)

    Herdeiro, Victor

    2017-09-01

    Herdeiro and Doyon [Phys. Rev. E 94, 043322 (2016), 10.1103/PhysRevE.94.043322] introduced a numerical recipe, dubbed uv sampler, offering precise estimations of the conformal field theory (CFT) data of the planar two-dimensional (2D) critical Ising model. It made use of scale invariance emerging at the critical point in order to sample finite sublattice marginals of the infinite plane Gibbs measure of the model by producing holographic boundary distributions. The main ingredient of the Markov chain Monte Carlo sampler is the invariance under dilation. This paper presents a generalization to higher dimensions with the critical 3D Ising model. This leads to numerical estimations of a subset of the CFT data—scaling weights and structure constants—through fitting of measured correlation functions. The results are shown to agree with the recent most precise estimations from numerical bootstrap methods [Kos, Poland, Simmons-Duffin, and Vichi, J. High Energy Phys. 08 (2016) 036, 10.1007/JHEP08(2016)036].

  17. Chain conformations of the component polymers and the microphase separation structures of homopolymer/block coplymer blends

    International Nuclear Information System (INIS)

    Torikai, Naoya; Mogi, Yasuhiro; Matsushita, Yushu; Noda, Ichiro; Han, C.C.

    1993-01-01

    Microdomain spacings of lamellar structures formed by styrene homopolymer/styrene-2-vinylpyridine diblock copolymer/2-vinylpyridine homopolymer blends were measured by small-angle X-ray scattering (SAXS) and single chain conformations of block copolymers in the same blend system were measured by small-angle neutron scattering (SANS). The molecular weight of diblock copolymers is 78K-72K, and three kinds of styrene homopolymer (S H ) and 2-vinylpyridine homopolymer (P H ) pairs were blended, their molecular weight ratios to that of host block chains were 0.17, 0.38, and 0.78, respectively. Two blend ratios of homopolymer (H)/block copolymer (B), i.e. 1/2 and 1/1 were examined. It was found that the domain spacings of all blends are larger than that of pure block copolymer and that they are increasing with increasing the molecular weight of homopolymers and/or with increasing the volume fraction of homopolymers. Further, block chains in the blends were confirmed to have almost the same chain dimension as that of block chain in pure block copolymer system in the direction parallel to the domain interface irrespective of molecular weight and volume fraction of homopolymers. (author)

  18. Conformation and structural changes of diblock copolymers with octopus-like micelle formation in the presence of external stimuli

    Science.gov (United States)

    Dammertz, K.; Saier, A. M.; Marti, O.; Amirkhani, M.

    2014-04-01

    External stimuli such as vapours and electric fields can be used to manipulate the formation of AB-diblock copolymers on surfaces. We study the conformational variation of PS-b-PMMA (polystyrene-block-poly(methyl methacrylate)), PS and PMMA adsorbed on mica and their response to saturated water or chloroform atmospheres. Using specimens with only partial polymer coverage, new unanticipated effects were observed. Water vapour, a non-solvent for all three polymers, was found to cause high surface mobility. In contrast, chloroform vapour (a solvent for all three polymers) proved to be less efficient. Furthermore, the influence of an additional applied electric field was investigated. A dc field oriented parallel to the sample surface induces the formation of polymer islands which assemble into wormlike chains. Moreover, PS-b-PMMA forms octopus-like micelles (OLMs) on mica. Under the external stimuli mentioned above, the wormlike formations of OLMs are able to align in the direction of the external electric field. In the absence of an electric field, the OLMs disaggregate and exhibit phase separated structures under chloroform vapour.

  19. Conformation and structural changes of diblock copolymers with octopus-like micelle formation in the presence of external stimuli

    International Nuclear Information System (INIS)

    Dammertz, K; Saier, A M; Marti, O; Amirkhani, M

    2014-01-01

    External stimuli such as vapours and electric fields can be used to manipulate the formation of AB-diblock copolymers on surfaces. We study the conformational variation of PS-b-PMMA (polystyrene-block-poly(methyl methacrylate)), PS and PMMA adsorbed on mica and their response to saturated water or chloroform atmospheres. Using specimens with only partial polymer coverage, new unanticipated effects were observed. Water vapour, a non-solvent for all three polymers, was found to cause high surface mobility. In contrast, chloroform vapour (a solvent for all three polymers) proved to be less efficient. Furthermore, the influence of an additional applied electric field was investigated. A dc field oriented parallel to the sample surface induces the formation of polymer islands which assemble into wormlike chains. Moreover, PS-b-PMMA forms octopus-like micelles (OLMs) on mica. Under the external stimuli mentioned above, the wormlike formations of OLMs are able to align in the direction of the external electric field. In the absence of an electric field, the OLMs disaggregate and exhibit phase separated structures under chloroform vapour. (paper)

  20. Balanced Electrostatic and Structural Forces Guide the Large Conformational Change Associated with Maturation of T = 4 Virus

    Science.gov (United States)

    Matsui, Tsutomu; Tsuruta, Hiro; Johnson, John E.

    2010-01-01

    Nudaurelia capensis omega virus has a well-characterized T = 4 capsid that undergoes a pH-dependent large conformational changes (LCC) and associated auto-catalytic cleavage of the subunit. We examined previously the particle size at different pH values and showed that maturation occurred at pH 5.5. We now characterized the LCC with time-resolved small-angle x-ray scattering and showed that there were three kinetic stages initiated with an incremental drop in pH: 1), a rapid (electrostatic and structural forces shapes the energy landscape of the LCC with the latter requiring annealing of portions of the subunit. Equilibrium experiments showed that many intermediate states could be populated with a homogeneous ensemble of particles by carefully controlling the pH. A titration curve for the LCC was generated that showed that the virtual pKa (i.e., the composite of all titratable residues that contribute to the LCC) is 5.8. PMID:20371334

  1. Conformational, structural, vibrational and quantum chemical analysis on 4-aminobenzohydrazide and 4-hydroxybenzohydrazide--a comparative study.

    Science.gov (United States)

    Arjunan, V; Jayaprakash, A; Carthigayan, K; Periandy, S; Mohan, S

    2013-05-01

    Experimental and theoretical quantum chemical studies were carried out on 4-hydroxybenzohydrazide (4HBH) and 4-aminobenzohydrazide (4ABH) using FTIR and FT-Raman spectral data. The structural characteristics and vibrational spectroscopic analysis were carried performed by quantum chemical methods with the hybrid exchange-correlation functional B3LYP using 6-31G(**), 6-311++G(**) and aug-cc-pVDZ basis sets. The most stable conformer of the title compounds have been determined from the analysis of potential energy surface. The stable molecular geometries, electronic and thermodynamic parameters, IR intensities, harmonic vibrational frequencies, depolarisation ratio and Raman intensities have been computed. Molecular electrostatic potential and frontier molecular orbitals were constructed to understand the electronic properties. The potential energy distributions (PEDs) were calculated to explain the mixing of fundamental modes. The theoretical geometrical parameters and the fundamental frequencies were compared with the experimental. The interactions of hydroxy and amino group substitutions on the characteristic vibrations of the ring and hydrazide group have been analysed. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. A Novel Inversion Method of Manufacturing Flaws in the Packaging of Conformal Load-Bearing Antenna Structure

    Directory of Open Access Journals (Sweden)

    P. Li

    2015-01-01

    Full Text Available Composite material is widely used in the conformal load-bearing antenna structure (CLAS, and the manufacturing flaws in the packaging process of the CLAS will lead to the degradation of its wave-transparent property. For this problem, a novel inverse method of the flaw’s dimension by antenna-radome system’s far field data has been proposed. Two steps are included in the inversion: the first one is the inversion from the far filed data to the transmission coefficient of the CLAS’s radome; the second one is the inversion from the transmission coefficient to the flaw’s dimension. The inversion also has a good potential for the separable multilayer composite material radome. A 12.5 GHz CLAS with microstrip antenna array is used in the simulation, which indicates the effectiveness of the novel inversion method. Finally, the error analysis of the inversion method is presented by numerical simulation; the results is that the inversed error could be less than 10%, if the measurement error of far field data is less than 0.45 dB in amplitude and ±5° in phase.

  3. Conformation radiotherapy and conformal radiotherapy

    International Nuclear Information System (INIS)

    Morita, Kozo

    1999-01-01

    In order to coincide the high dose region to the target volume, the 'Conformation Radiotherapy Technique' using the multileaf collimator and the device for 'hollow-out technique' was developed by Prof. S. Takahashi in 1960. This technique can be classified a type of 2D-dynamic conformal RT techniques. By the clinical application of this technique, the late complications of the lens, the intestine and the urinary bladder after radiotherapy for the maxillary cancer and the cervical cancer decreased. Since 1980's the exact position and shape of the tumor and the surrounding normal tissues can be easily obtained by the tremendous development of the CT/MRI imaging technique. As a result, various kinds of new conformal techniques such as the 3D-CRT, the dose intensity modulation, the tomotherapy have been developed since the beginning of 1990'. Several 'dose escalation study with 2D-/3D conformal RT' is now under way to improve the treatment results. (author)

  4. Local chromatin structure of heterochromatin regulates repeated DNA stability, nucleolus structure, and genome integrity

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Jamy C. [Univ. of California, Berkeley, CA (United States)

    2007-01-01

    Heterochromatin constitutes a significant portion of the genome in higher eukaryotes; approximately 30% in Drosophila and human. Heterochromatin contains a high repeat DNA content and a low density of protein-encoding genes. In contrast, euchromatin is composed mostly of unique sequences and contains the majority of single-copy genes. Genetic and cytological studies demonstrated that heterochromatin exhibits regulatory roles in chromosome organization, centromere function and telomere protection. As an epigenetically regulated structure, heterochromatin formation is not defined by any DNA sequence consensus. Heterochromatin is characterized by its association with nucleosomes containing methylated-lysine 9 of histone H3 (H3K9me), heterochromatin protein 1 (HP1) that binds H3K9me, and Su(var)3-9, which methylates H3K9 and binds HP1. Heterochromatin formation and functions are influenced by HP1, Su(var)3-9, and the RNA interference (RNAi) pathway. My thesis project investigates how heterochromatin formation and function impact nuclear architecture, repeated DNA organization, and genome stability in Drosophila melanogaster. H3K9me-based chromatin reduces extrachromosomal DNA formation; most likely by restricting the access of repair machineries to repeated DNAs. Reducing extrachromosomal ribosomal DNA stabilizes rDNA repeats and the nucleolus structure. H3K9me-based chromatin also inhibits DNA damage in heterochromatin. Cells with compromised heterochromatin structure, due to Su(var)3-9 or dcr-2 (a component of the RNAi pathway) mutations, display severe DNA damage in heterochromatin compared to wild type. In these mutant cells, accumulated DNA damage leads to chromosomal defects such as translocations, defective DNA repair response, and activation of the G2-M DNA repair and mitotic checkpoints that ensure cellular and animal viability. My thesis research suggests that DNA replication, repair, and recombination mechanisms in heterochromatin differ from those in

  5. The flow field structure of highly stabilized partially premixed flames in a concentric flow conical nozzle burner with coflow

    KAUST Repository

    Elbaz, Ayman M.; Zayed, M.F.; Samy, M.; Roberts, William L.; Mansour, Mohy S.

    2015-01-01

    The stability limits, the stabilization mechanism, and the flow field structure of highly stabilized partially premixed methane flames in a concentric flow conical nozzle burner with air co-flow have been investigated and presented in this work

  6. Primary structure and conformational analysis of peptide methionine-tyrosine, a peptide related to neuropeptide Y and peptide YY isolated from lamprey intestine

    DEFF Research Database (Denmark)

    Conlon, J M; Bjørnholm, B; Jørgensen, Flemming Steen

    1991-01-01

    A peptide belonging to the pancreatic-polypeptide-fold family of regulatory peptides has been isolated from the intestine of an Agnathan, the sea lamprey (Petromyzon marinus). The primary structure of the peptide (termed peptide methionine-tyrosine) was established as Met-Pro-Pro-Lys-Pro-Asp-Asn-...... in a preferred structure in which the conformation of the beta-turn between the two helical domains (residues 9-14) is appreciably different....

  7. Extending Entropy Stability Measure To External Debt Structure ...

    African Journals Online (AJOL)

    This study focuses on the measure of stability of external debt using entropy. This is achieved by modifying the conglomerate of Shannon and Boltzmann entropy. This modification rectifies the limitations of these models. Practical illustration of the modified model is also given to justify its use. Journal of Science ...

  8. Structural stability of high entropy alloys under pressure and temperature

    DEFF Research Database (Denmark)

    Ahmad, Azkar S.; Su, Y.; Liu, S. Y.

    2017-01-01

    The stability of high-entropy alloys (HEAs) is a key issue before their selection for industrial applications. In this study, in-situ high-pressure and high-temperature synchrotron radiation X-ray diffraction experiments have been performed on three typical HEAs Ni20Co20Fe20Mn20Cr20, Hf25Nb25Zr25Ti...

  9. Influence of structure of crown ethers on their radiation stability

    International Nuclear Information System (INIS)

    Grigor'ev, E.I.; Myasoedova, T.G.; Nesterov, S.V.; Trakhtenberg, L.I.

    1988-01-01

    Primary products of γ-radiolysis of crown ethers with the same size of the macrocyclic ring and different substituents were studied by EPR and mass spectrometry. It was shown that introduction of substituents into the polyether ring increases the radiation stability of crown ethers due to intramolecular transfer of energy from the polyether ring to a substituent

  10. Structure and Stability of Complex Coacervate Core Micelles with Lysozyme

    NARCIS (Netherlands)

    Lindhoud, Saskia; de Vries, Renko; Norde, Willem; Cohen Stuart, Martinus Abraham

    2007-01-01

    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA42PAAm417 and

  11. Structure and stability of complex coacervate core micelles with lysozyme

    NARCIS (Netherlands)

    Lindhoud, Saskia; de Vries, Renko; Norde, Willem; Cohen Stuart, Martien A.

    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA(42)PAAm(417)

  12. Conformal Gravity

    International Nuclear Information System (INIS)

    Hooft, G.

    2012-01-01

    The dynamical degree of freedom for the gravitational force is the metric tensor, having 10 locally independent degrees of freedom (of which 4 can be used to fix the coordinate choice). In conformal gravity, we split this field into an overall scalar factor and a nine-component remainder. All unrenormalizable infinities are in this remainder, while the scalar component can be handled like any other scalar field such as the Higgs field. In this formalism, conformal symmetry is spontaneously broken. An imperative demand on any healthy quantum gravity theory is that black holes should be described as quantum systems with micro-states as dictated by the Hawking-Bekenstein theory. This requires conformal symmetry that may be broken spontaneously but not explicitly, and this means that all conformal anomalies must cancel out. Cancellation of conformal anomalies yields constraints on the matter sector as described by some universal field theory. Thus black hole physics may eventually be of help in the construction of unified field theories. (author)

  13. Multiple spectroscopic studies of the structural conformational changes of human serum albumin—Essential oil based nanoemulsions conjugates

    International Nuclear Information System (INIS)

    Sekar, Gajalakshmi; Sugumar, Saranya; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2015-01-01

    Nanoemulsions have numerous biomedical applications. For the first time, we have investigated the effects of orange and eucalyptus essential oil based nanoemulsions towards the structural aspect of human serum albumin (HSA). Quenching effect of nanoemulsion against the intrinsic fluorescence potential of tryptophan and tyrosine residues were evidenced from the fluorescence spectroscopic analysis. Static quenching mechanism was found to lead the binding of HSA–nanoemulsion systems. Synchronous and three dimensional spectroscopic studies have revealed the possible changes to the aromatic environment of HSA by the nanoemulsion. UV–Visible spectroscopic studies have confirmed the existence of the ground state complex formation between HSA and the surface of nanoemulsions by exhibiting the hyper-chromic effect in a concentration dependant manner. FTIR spectroscopy revealed the slight alteration in the Amide I, II and III bands of HSA after interaction. FT-Raman spectroscopy showed the decrease in the Raman intensity of the aromatic amino acid residues and shift in the amide bands of HSA upon binding with the nanoemulsion. Dichoric band obtained from the far UV-CD spectra at 208 and 222 nm of HSA showed the corresponding decrease in the alpha-helical contents upon interaction with nanoemulsions. Near UV-CD spectra also showed the prominent changes in the aromatic positions of the amino acid residues of HSA on binding with nanoemulsions. The above study has extrapolated the side effect analysis of the nanoemulsions in pharmaceutical applications in vitro in reference to their interaction with serum proteins. - Highlights: • Orange and eucalyptus oil based nanoemulsions were formulated and characterized. • UV–Visible spectroscopy confirmed the ground state complex formation. • Fluorescence spectroscopy confirmed the molecular conformational changes. • FTIR spectroscopy deep-rooted the alteration in the amide bands of HSA. • FT-Raman spectroscopy established

  14. Multiple spectroscopic studies of the structural conformational changes of human serum albumin—Essential oil based nanoemulsions conjugates

    Energy Technology Data Exchange (ETDEWEB)

    Sekar, Gajalakshmi; Sugumar, Saranya; Mukherjee, Amitava; Chandrasekaran, Natarajan, E-mail: nchandra40@hotmail.com

    2015-05-15

    Nanoemulsions have numerous biomedical applications. For the first time, we have investigated the effects of orange and eucalyptus essential oil based nanoemulsions towards the structural aspect of human serum albumin (HSA). Quenching effect of nanoemulsion against the intrinsic fluorescence potential of tryptophan and tyrosine residues were evidenced from the fluorescence spectroscopic analysis. Static quenching mechanism was found to lead the binding of HSA–nanoemulsion systems. Synchronous and three dimensional spectroscopic studies have revealed the possible changes to the aromatic environment of HSA by the nanoemulsion. UV–Visible spectroscopic studies have confirmed the existence of the ground state complex formation between HSA and the surface of nanoemulsions by exhibiting the hyper-chromic effect in a concentration dependant manner. FTIR spectroscopy revealed the slight alteration in the Amide I, II and III bands of HSA after interaction. FT-Raman spectroscopy showed the decrease in the Raman intensity of the aromatic amino acid residues and shift in the amide bands of HSA upon binding with the nanoemulsion. Dichoric band obtained from the far UV-CD spectra at 208 and 222 nm of HSA showed the corresponding decrease in the alpha-helical contents upon interaction with nanoemulsions. Near UV-CD spectra also showed the prominent changes in the aromatic positions of the amino acid residues of HSA on binding with nanoemulsions. The above study has extrapolated the side effect analysis of the nanoemulsions in pharmaceutical applications in vitro in reference to their interaction with serum proteins. - Highlights: • Orange and eucalyptus oil based nanoemulsions were formulated and characterized. • UV–Visible spectroscopy confirmed the ground state complex formation. • Fluorescence spectroscopy confirmed the molecular conformational changes. • FTIR spectroscopy deep-rooted the alteration in the amide bands of HSA. • FT-Raman spectroscopy established

  15. Exploring the atomic structure and conformational flexibility of a 320 Å long engineered viral fiber using X-ray crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Bhardwaj, Anshul [Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107 (United States); Casjens, Sherwood R. [University of Utah School of Medicine, Salt Lake City, UT 84112 (United States); Cingolani, Gino, E-mail: gino.cingolani@jefferson.edu [Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107 (United States)

    2014-02-01

    This study presents the crystal structure of a ∼320 Å long protein fiber generated by in-frame extension of its repeated helical coiled-coil core. Protein fibers are widespread in nature, but only a limited number of high-resolution structures have been determined experimentally. Unlike globular proteins, fibers are usually recalcitrant to form three-dimensional crystals, preventing single-crystal X-ray diffraction analysis. In the absence of three-dimensional crystals, X-ray fiber diffraction is a powerful tool to determine the internal symmetry of a fiber, but it rarely yields atomic resolution structural information on complex protein fibers. An 85-residue-long minimal coiled-coil repeat unit (MiCRU) was previously identified in the trimeric helical core of tail needle gp26, a fibrous protein emanating from the tail apparatus of the bacteriophage P22 virion. Here, evidence is provided that an MiCRU can be inserted in frame inside the gp26 helical core to generate a rationally extended fiber (gp26-2M) which, like gp26, retains a trimeric quaternary structure in solution. The 2.7 Å resolution crystal structure of this engineered fiber, which measures ∼320 Å in length and is only 20–35 Å wide, was determined. This structure, the longest for a trimeric protein fiber to be determined to such a high resolution, reveals the architecture of 22 consecutive trimerization heptads and provides a framework to decipher the structural determinants for protein fiber assembly, stability and flexibility.

  16. Exploring the atomic structure and conformational flexibility of a 320 Å long engineered viral fiber using X-ray crystallography

    International Nuclear Information System (INIS)

    Bhardwaj, Anshul; Casjens, Sherwood R.; Cingolani, Gino

    2014-01-01

    This study presents the crystal structure of a ∼320 Å long protein fiber generated by in-frame extension of its repeated helical coiled-coil core. Protein fibers are widespread in nature, but only a limited number of high-resolution structures have been determined experimentally. Unlike globular proteins, fibers are usually recalcitrant to form three-dimensional crystals, preventing single-crystal X-ray diffraction analysis. In the absence of three-dimensional crystals, X-ray fiber diffraction is a powerful tool to determine the internal symmetry of a fiber, but it rarely yields atomic resolution structural information on complex protein fibers. An 85-residue-long minimal coiled-coil repeat unit (MiCRU) was previously identified in the trimeric helical core of tail needle gp26, a fibrous protein emanating from the tail apparatus of the bacteriophage P22 virion. Here, evidence is provided that an MiCRU can be inserted in frame inside the gp26 helical core to generate a rationally extended fiber (gp26-2M) which, like gp26, retains a trimeric quaternary structure in solution. The 2.7 Å resolution crystal structure of this engineered fiber, which measures ∼320 Å in length and is only 20–35 Å wide, was determined. This structure, the longest for a trimeric protein fiber to be determined to such a high resolution, reveals the architecture of 22 consecutive trimerization heptads and provides a framework to decipher the structural determinants for protein fiber assembly, stability and flexibility

  17. Structure and stability of complexes of agmatine with some functional receptor residues of proteins

    Science.gov (United States)

    Remko, Milan; Broer, Ria; Remková, Anna; Van Duijnen, Piet Th.

    2017-04-01

    The paper reports the results of a theoretical study of the conformational behavior and basicity of biogenic amine agmatine. The complexes modelling of agmatine - protein interaction are also under scrutiny of our investigation using the Becke3LYP and B97D levels of the density functional theory. The relative stabilities (Gibbs energies) of individual complexes are by both DFT methods described equally. Hydration has a dramatic effect on the hydrogen bonded complexes studied. The pairing acidic carboxylate group with different agmatine species resulted in charged hydrogen bond complexes containing negatively charged acetate species acting as proton acceptors.

  18. Squaraine rotaxanes with boat conformation macrocycles.

    Science.gov (United States)

    Fu, Na; Baumes, Jeffrey M; Arunkumar, Easwaran; Noll, Bruce C; Smith, Bradley D

    2009-09-04

    Mechanical encapsulation of fluorescent, deep-red bis(anilino)squaraine dyes inside Leigh-type tetralactam macrocycles produces interlocked squaraine rotaxanes. The surrounding macrocycles are flexible and undergo rapid exchange of chair and boat conformations in solution. A series of X-ray crystal structures show how the rotaxane co-conformational exchange process involves simultaneous lateral oscillation of the macrocycle about the center of the encapsulated squaraine thread. Rotaxane macrocycles with 1,4-phenylene sidewalls and 2,6-pyridine dicarboxamide bridging units are more likely to adopt boat conformations in the solid state than analogous squaraine rotaxane systems with isophthalamide-containing macrocycles. A truncated squaraine dye, with a secondary amine attached directly to the central C(4)O(2) core, is less electrophilic than the extended bis(anilino)squaraine analogue, but it is still susceptible to chemical and photochemical bleaching. Its stability is greatly enhanced when it is encapsulated as an interlocked squaraine rotaxane. An X-ray crystal structure of this truncated squaraine rotaxane shows the macrocycle in a boat conformation, and NMR studies indicate that the boat is maintained in solution. Encapsulation as a rotaxane increases the dye's brightness by a factor of 6. The encapsulation process appears to constrain the dye and reduce deformation of the chromophore from planarity. This study shows how mechanical encapsulation as a rotaxane can be used as a rational design parameter to fine-tune the chemical and photochemical properties of squaraine dyes.

  19. Structural characterization of POM6 Fab and mouse prion protein complex identifies key regions for prions conformational conversion.

    Science.gov (United States)

    Baral, Pravas Kumar; Swayampakula, Mridula; Aguzzi, Adriano; James, Michael N G

    2018-05-01

    Conversion of the cellular prion protein PrP C into its pathogenic isoform PrP S c is the hallmark of prion diseases, fatal neurodegenerative diseases affecting many mammalian species including humans. Anti-prion monoclonal antibodies can arrest the progression of prion diseases by stabilizing the cellular form of the prion protein. Here, we present the crystal structure of the POM6 Fab fragment, in complex with the mouse prion protein (moPrP). The prion epitope of POM6 is in close proximity to the epitope recognized by the purportedly toxic antibody fragment, POM1 Fab also complexed with moPrP. The POM6 Fab recognizes a larger binding interface indicating a likely stronger binding compared to POM1. POM6 and POM1 exhibit distinct biological responses. Structural comparisons of the bound mouse prion proteins from the POM6 Fab:moPrP and POM1 Fab:moPrP complexes reveal several key regions of the prion protein that might be involved in initiating mis-folding events. The structural data of moPrP:POM6 Fab complex are available in the PDB under the accession number www.rcsb.org/pdb/search/structidSearch.do?structureId=6AQ7. © 2018 Federation of European Biochemical Societies.

  20. Structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase in complex with the feedback inhibitor CoA reveals only one active-site conformation

    Energy Technology Data Exchange (ETDEWEB)

    Wubben, T.; Mesecar, A.D. (Purdue); (UIC)

    2014-10-02

    Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway, reversibly transferring an adenylyl group from ATP to 4'-phosphopantetheine to form dephosphocoenzyme A (dPCoA). To complement recent biochemical and structural studies on Mycobacterium tuberculosis PPAT (MtPPAT) and to provide further insight into the feedback regulation of MtPPAT by CoA, the X-ray crystal structure of the MtPPAT enzyme in complex with CoA was determined to 2.11 {angstrom} resolution. Unlike previous X-ray crystal structures of PPAT-CoA complexes from other bacteria, which showed two distinct CoA conformations bound to the active site, only one conformation of CoA is observed in the MtPPAT-CoA complex.

  1. Stability and recovery of DNA origami structure with cation concentration

    Science.gov (United States)

    Chen, Yi; Wang, Ping; Liu, Yang; Liu, Ting; Xu, Yan; Zhu, Shanshan; Zhu, Jun; Ye, Kai; Huang, Guang; Dannong, He

    2018-01-01

    We synthesized triangular and rectangular DNA origami nanostructures and investigated the stability and recovery of them under low cation concentration. Our results demonstrated that the origami nanostructures would melt when incubated in low cation concentration, and recover whilst kept in the concentration for less than 10 min. However, extending the incubation time would lead to irreversible melting. Our results show the possibility of application of DNA origami nanostructures for things such as a sensor for cation concentration response, etc.

  2. First Principles Prediction of Structure, Structure Selectivity, and Thermodynamic Stability under Realistic Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Ceder, Gerbrand [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Materials and Engineering

    2018-01-28

    Novel materials are often the enabler for new energy technologies. In ab-initio computational materials science, method are developed to predict the behavior of materials starting from the laws of physics, so that properties can be predicted before compounds have to be synthesized and tested. As such, a virtual materials laboratory can be constructed, saving time and money. The objectives of this program were to develop first-principles theory to predict the structure and thermodynamic stability of materials. Since its inception the program focused on the development of the cluster expansion to deal with the increased complexity of complex oxides. This research led to the incorporation of vibrational degrees of freedom in ab-initio thermodynamics, developed methods for multi-component cluster expansions, included the explicit configurational degrees of freedom of localized electrons, developed the formalism for stability in aqueous environments, and culminated in the first ever approach to produce exact ground state predictions of the cluster expansion. Many of these methods have been disseminated to the larger theory community through the Materials Project, pymatgen software, or individual codes. We summarize three of the main accomplishments.

  3. Frame Stability of Tunnel‐Structured Cryptomelane Nanofibers: The Role of Tunnel Cations

    DEFF Research Database (Denmark)

    Gao, Tao; Norby, Poul

    2013-01-01

    precursor to the tunnel‐structured cryptomelane, in which the K+ ions play important roles in templating and stabilizing the tunneled framework. The presence of tunnel K+ ions also enhances the frame stability of the cryptomelane nanofibers at elevated temperatures. The formation of a layered KxMn2O4 (x ≈ 0...

  4. Calcium binding promotes prion protein fragment 90-231 conformational change toward a membrane destabilizing and cytotoxic structure.

    Directory of Open Access Journals (Sweden)

    Sacha Sorrentino

    Full Text Available The pathological form of prion protein (PrP(Sc, as other amyloidogenic proteins, causes a marked increase of membrane permeability. PrP(Sc extracted from infected Syrian hamster brains induces a considerable change in membrane ionic conductance, although the contribution of this interaction to the molecular mechanism of neurodegeneration process is still controversial. We previously showed that the human PrP fragment 90-231 (hPrP₉₀₋₂₃₁ increases ionic conductance across artificial lipid bilayer, in a calcium-dependent manner, producing an alteration similar to that observed for PrP(Sc. In the present study we demonstrate that hPrP₉₀₋₂₃₁, pre-incubated with 10 mM Ca⁺⁺ and then re-suspended in physiological external solution increases not only membrane conductance but neurotoxicity as well. Furthermore we show the existence of a direct link between these two effects as demonstrated by a highly statistically significant correlation in several experimental conditions. A similar correlation between increased membrane conductance and cell degeneration has been observed assaying hPrP₉₀₋₂₃₁ bearing pathogenic mutations (D202N and E200K. We also report that Ca⁺⁺ binding to hPrP₉₀₋₂₃₁ induces a conformational change based on an alteration of secondary structure characterized by loss of alpha-helix content causing hydrophobic amino acid exposure and proteinase K resistance. These features, either acquired after controlled thermal denaturation or induced by D202N and E200K mutations were previously identified as responsible for hPrP₉₀₋₂₃₁ cytotoxicity. Finally, by in silico structural analysis, we propose that Ca⁺⁺ binding to hPrP₉₀₋₂₃₁ modifies amino acid orientation, in the same way induced by E200K mutation, thus suggesting a pathway for the structural alterations responsible of PrP neurotoxicity.

  5. Market structure and the stability and volatility of electricity prices

    International Nuclear Information System (INIS)

    Bask, Mikael; Widerberg, Anna

    2009-01-01

    By using a novel approach in this paper, (λ,σ 2 )-analysis, we have found that electricity prices most of the time have increased in stability and decreased in volatility when the Nordic power market has expanded and the degree of competition has increased. That electricity prices at Nord Pool have been generated by a stochastic dynamic system that most often has become more stable during the step-wise integration of the Nordic power market means that this market is less sensitive to shocks after the integration process than it was before this process. This is good news

  6. Structural stability of DNA origami nanostructures in the presence of chaotropic agents.

    Science.gov (United States)

    Ramakrishnan, Saminathan; Krainer, Georg; Grundmeier, Guido; Schlierf, Michael; Keller, Adrian

    2016-05-21

    DNA origami represent powerful platforms for single-molecule investigations of biomolecular processes. The required structural integrity of the DNA origami may, however, pose significant limitations regarding their applicability, for instance in protein folding studies that require strongly denaturing conditions. Here, we therefore report a detailed study on the stability of 2D DNA origami triangles in the presence of the strong chaotropic denaturing agents urea and guanidinium chloride (GdmCl) and its dependence on concentration and temperature. At room temperature, the DNA origami triangles are stable up to at least 24 h in both denaturants at concentrations as high as 6 M. At elevated temperatures, however, structural stability is governed by variations in the melting temperature of the individual staple strands. Therefore, the global melting temperature of the DNA origami does not represent an accurate measure of their structural stability. Although GdmCl has a stronger effect on the global melting temperature, its attack results in less structural damage than observed for urea under equivalent conditions. This enhanced structural stability most likely originates from the ionic nature of GdmCl. By rational design of the arrangement and lengths of the individual staple strands used for the folding of a particular shape, however, the structural stability of DNA origami may be enhanced even further to meet individual experimental requirements. Overall, their high stability renders DNA origami promising platforms for biomolecular studies in the presence of chaotropic agents, including single-molecule protein folding or structural switching.

  7. Conformational analysis of lignin models

    International Nuclear Information System (INIS)

    Santos, Helio F. dos

    2001-01-01

    The conformational equilibrium for two 5,5' biphenyl lignin models have been analyzed using a quantum mechanical semiempirical method. The gas phase and solution structures are discussed based on the NMR and X-ray experimental data. The results obtained showed that the observed conformations are solvent-dependent, being the geometries and the thermodynamic properties correlated with the experimental information. This study shows how a systematic theoretical conformational analysis can help to understand chemical processes at a molecular level. (author)

  8. Broadband Liquid Dampers to Stabilize Flexible Spacecraft Structures

    NARCIS (Netherlands)

    Kuiper, J.M.

    2012-01-01

    Mass-spring and liquid dampers enable structural vibration control to attenuate single, coupled lateral and torsional vibrations in diverse structures. Out of these, the passively tuned liquid damper (TLD) class is wanted due to its broad applicability, extreme reliability, robustness, long life

  9. The structure and stability of common mental disorders - The NEMESIS Study

    NARCIS (Netherlands)

    Vollebergh, W.A.M.; Iedema, J; Bijl, R.V.; de Graaf, R.; Smit, F.; Ormel, J.

    Background: We analyzed the underlying latent structure of 12-month DSM-III-R diagnoses of 9 common disorders for the general population in the Netherlands. In addition, we sought to establish (1) the stability of the latent structure underlying mental disorders across a 1-year period (structural

  10. Stability of material in dynamics of structural organization

    Directory of Open Access Journals (Sweden)

    Vyrovoy Valery

    2017-01-01

    Full Text Available Formation of the scientific ideology is based on the basic model of the structured medium and demands the formalization of the term «structure». The objects-systems are offered to be present in the form of models. It is shown that the mechanism of structure formation on the solid level where gravity prevails differs from mechanism of structure formation at the level where forces of interparticle interactions dominate. It is asserted that geometrical characteristics of products define conditions of the organization of its integral structure. Rather independent coexistence of various solid levels assumes spontaneous realization of various interconnected events which provides the wholeness and safe functioning of a construction-system.

  11. Theory of lithium islands and monolayers: Electronic structure and stability

    International Nuclear Information System (INIS)

    Quassowski, S.; Hermann, K.

    1995-01-01

    Systematic calculations on planar clusters and monolayers of lithium are performed to study geometries and stabilities of the clusters as well as their convergence behavior with increasing cluster size. The calculations are based on ab initio methods using density-functional theory within the local-spin-density approximation for exchange and correlation. The optimized nearest-neighbor distances d NN of the Li n clusters, n=1,...,25, of both hexagonal and square geometry increase with cluster size, converging quite rapidly towards the monolayer results. Further, the cluster cohesive energies E c increase with cluster size and converge towards the respective monolayer values that form upper bounds. Clusters of hexagonal geometry are found to be more stable than square clusters of comparable size, consistent with the monolayer results. The size dependence of the cluster cohesive energies can be described approximately by a coordination model based on the concept of pairwise additive nearest-neighbor binding. This indicates that the average binding in the Li n clusters and their relative stabilities can be explained by simple geometric effects which derive from the nearest-neighbor coordination

  12. Stabilization

    Directory of Open Access Journals (Sweden)

    Muhammad H. Al-Malack

    2016-07-01

    Full Text Available Fuel oil flyash (FFA produced in power and water desalination plants firing crude oils in the Kingdom of Saudi Arabia is being disposed in landfills, which increases the burden on the environment, therefore, FFA utilization must be encouraged. In the current research, the effect of adding FFA on the engineering properties of two indigenous soils, namely sand and marl, was investigated. FFA was added at concentrations of 5%, 10% and 15% to both soils with and without the addition of Portland cement. Mixtures of the stabilized soils were thoroughly evaluated using compaction, California Bearing Ratio (CBR, unconfined compressive strength (USC and durability tests. Results of these tests indicated that stabilized sand mixtures could not attain the ACI strength requirements. However, marl was found to satisfy the ACI strength requirement when only 5% of FFA was added together with 5% of cement. When the FFA was increased to 10% and 15%, the mixture’s strength was found to decrease to values below the ACI requirements. Results of the Toxicity Characteristics Leaching Procedure (TCLP, which was performed on samples that passed the ACI requirements, indicated that FFA must be cautiously used in soil stabilization.

  13. A chemometric analysis of ligand-induced changes in intrinsic fluorescence of folate binding protein indicates a link between altered conformational structure and physico-chemical characteristics

    DEFF Research Database (Denmark)

    Bruun, Susanne W; Holm, Jan; Hansen, Steen Ingemann

    2009-01-01

    Ligand binding alters the conformational structure and physico-chemical characteristics of bovine folate binding protein (FBP). For the purpose of achieving further information we analyzed ligand (folate and methotrexate)-induced changes in the fluorescence landscape of FBP. Fluorescence excitation...... of folate accords fairly well with the disappearance of strongly hydrophobic tryptophan residues from the solvent-exposed surface of FBP. The PARAFAC has thus proven useful to establish a hitherto unexplained link between parallel changes in conformational structure and physico-chemical characteristics...... of FBP induced by folate binding. Parameters for ligand binding derived from PARAFAC analysis of the fluorescence data were qualitatively and quantitatively similar to those obtained from binding of radiofolate to FBP. Herein, methotrexate exhibited a higher affinity for FBP than in competition...

  14. Small Angle Neutron Scattering Studies of the Counterion Effects on the Molecular Conformation and Structure of Charged G4 PAMAM Dendrimers in Aqueous Solutions

    International Nuclear Information System (INIS)

    Chen, Wei-Ren

    2007-01-01

    The structural properties of generation 4 (G4) poly(amidoamine) starburst dendrimers (PAMAM) with an ethylenediamine ne (EDA) central core in D O 2 solutions have been studied by small angle neutron scattering. Upon the addition of DCl , SANS patterns show a pronounced inter-particle 2 correlation peaks due to the strong repulsion introduced by the protonation of the amino groups of the dendrimers. By solving the Ornstein-Zernike integral equation (OZ) with hypernetted chain closure (HNC), the dendrimer-dendrimer er structure factor S(Q) is determined and used to fit the experimental data. Quantitative information such as the effective charge per dendrimer and its conformational change at different conditions can be obtained. The results obtained show clear evidence that significant counterion association occurs, strongly mediating the inter-dendrimer interaction. The influence of interplay between counterions and molecular protonation of dendrimers has strong effect on the dendrimer conformation and effective interaction.

  15. Structure-based network analysis of activation mechanisms in the ErbB family of receptor tyrosine kinases: the regulatory spine residues are global mediators of structural stability and allosteric interactions.

    Directory of Open Access Journals (Sweden)

    Kevin A James

    Full Text Available The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced "superacceptor" activity in oncogenic EGFR dimers. We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. The results of this study have pointed to a central role of the conserved His-Arg-Asp (HRD motif in the catalytic loop and the Asp-Phe-Gly (DFG motif as key mediators of structural stability and allosteric communications in the ErbB kinases. We have determined that residues that are indispensable for kinase regulation and catalysis often corresponded to the high centrality nodes within the protein structure network and could be distinguished by their unique network signatures. The optimal communication pathways are also controlled by these nodes and may ensure efficient allosteric signaling in the functional kinase state. Structure-based network analysis has quantified subtle effects of ATP binding on conformational dynamics and stability of the EGFR structures. Consistent with the NMR studies, we have found that nucleotide-induced modulation of the residue interaction networks is not

  16. Conformational characterization of nerve growth factor-β reveals that its regulatory pro-part domain stabilizes three loop regions in its mature part

    DEFF Research Database (Denmark)

    Trabjerg, Esben; Kartberg, Fredrik; Christensen, Søren

    2017-01-01

    of the common neurotrophin receptor (p75NTR) and sortilin. The overexpression of both proNGF and sortilin has been associated with several neurodegenerative diseases. Insights into the conformational differences between proNGF and NGF are central to a better understanding of the opposing mechanisms of action...

  17. Structure and Stability of Pt-Y Alloy Particles for Oxygen Reduction Studied by Electron Microscopy

    DEFF Research Database (Denmark)

    Deiana, Davide; Wagner, Jakob Birkedal; Hansen, Thomas Willum

    2015-01-01

    Platinum-yttrium alloy nanoparticles show both a high activity and stability for the oxygen reduction reaction. The catalysts were prepared by magnetron sputter aggregation and mass filtration providing a model catalyst system with a narrow size distribution. The structure and stability of nanost...... the catalyst after reaction and after aging tests shows the development of a core-shell type structure after being exposed to reaction conditions....

  18. Structure and Mechanical Properties of Al-Cu-Fe-X Alloys with Excellent Thermal Stability

    OpenAIRE

    Školáková, Andrea; Novák, Pavel; Mejzlíková, Lucie; Průša, Filip; Salvetr, Pavel; Vojtěch, Dalibor

    2017-01-01

    In this work, the structure and mechanical properties of innovative Al-Cu-Fe based alloys were studied. We focused on preparation and characterization of rapidly solidified and hot extruded Al-Cu-Fe, Al-Cu-Fe-Ni and Al-Cu-Fe-Cr alloys. The content of transition metals affects mechanical properties and structure. For this reason, microstructure, phase composition, hardness and thermal stability have been investigated in this study. The results showed exceptional thermal stability of these allo...

  19. The structure of nuclei far from beta stability

    International Nuclear Information System (INIS)

    Zganjar, E.F.

    1990-01-01

    This report discusses the following topics: shape coexistence, intruder states, and E0 transitions; the Ir isotopes; the Pt isotopes; the Au isotopes; the Hg isotopes; the Tl isotopes; decay properties of 153 Yb and 153 Tm; non-yrast levels structure of 135 Nd via beta decay of 135 Pm; decay of mass-separated 137 Eu and 137 Sm; structure of 130,132 Ce, 132,134 Nd, and 134 Pm; decay of 127 Cs to levels of odd-neutron 127 Xe; level structure of 119 Te; conversion electron spectroscopy in 116 Xe and 126 Xe; signature of the shape coexistence in 72 Kr; identification of transitions in 73 Kr and search for large oblate; high spin states and multiple band structure in 68 Ge; high spin states in 65 Ga and 67 Ga; electron spectroscopy; ion sources; and the on-line nuclear orientation facility

  20. Configurational Model for Conductivity of Stabilized Fluorite Structure Oxides

    DEFF Research Database (Denmark)

    Poulsen, Finn Willy

    1981-01-01

    The formalism developed here furnishes means by which ionic configurations, solid solution limits, and conductivity mechanisms in doped fluorite structures can be described. The present model differs markedly from previous models but reproduces qualitatively reality. The analysis reported...

  1. Design Formulae for Hydraulic Stability and Structural Integrity of Dolos Breakwater Round-Heads

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Jensen, Jacob Birk; Liu, Z.

    1995-01-01

    A rational design of Dolos armour unit should incorporate both the hydraulic stability and the structural integrity. The previous tests performed by Aalborg University (AU) resulted in design formulae for the trunk of a 1:1.5 slope Dolos breakwater without superstructure including both...... the hydraulic stability and the structural integrity. The objective of the round-head tests is to produce similar design formulae for Dolos armour in around-head. The tests will also include examinations of the hydraulic stability and run-up for a trunk section adjacent to the round-head. A run-up formula...

  2. Critical Role of Crystalline Anisotropy in the Stability of Cellular Array Structures in Directional Solidification

    International Nuclear Information System (INIS)

    Kopczynski, P.; Rappel, W.; Karma, A.

    1996-01-01

    We calculate numerically the full Floquet-Bloch stability spectrum of cellular array structures in a symmetric model of directional solidification. Our results demonstrate that crystalline anisotropy critically influences the stability of these structures. Without anisotropy, the stability balloon of cells in the plane of wave number and velocity closes near the onset of morphological instability. With a finite, but even small, amount of anisotropy this balloon remains open and a band of stable solutions persists for higher velocities into a deep cell regime. The width of the balloon depends critically on the anisotropy strength. copyright 1996 The American Physical Society

  3. Oxidative stability of structured lipids produced from sunflower oil and caprylic acid

    DEFF Research Database (Denmark)

    Timm Heinrich, Maike; Xu, Xuebing; Nielsen, Nina Skall

    2003-01-01

    Traditional sunflower oil (SO), randomized lipid (RL) and specific structured lipid (SL), both produced from SO and tricaprylin/caprylic acid, respectively, were stored for up to 12 wk to compare their oxidative stabilities by chemical and sensory analyses. Furthermore, the effect of adding...... a commercial antioxidant blend Grindox 117 (propyl gallate/citric acid/ascorbyl palmitate) or gallic acid to the SL was investigated. The lipid type affected the oxidative stability: SL was less stable than SO and RL. The reduced stability was most likely caused by both the structure of the lipid...

  4. The Structure and Stability of Molybdenum Ditelluride Thin Films

    Directory of Open Access Journals (Sweden)

    Zhouling Wang

    2014-01-01

    Full Text Available Molybdenum-tellurium alloy thin films were fabricated by electron beam evaporation and the films were annealed in different conditions in N2 ambient. The hexagonal molybdenum ditelluride thin films with well crystallization annealed at 470°C or higher were obtained by solid state reactions. Thermal stability measurements indicate the formation of MoTe2 took place at about 350°C, and a subtle weight-loss was in the range between 30°C and 500°C. The evolution of the chemistry for Mo-Te thin films was performed to investigate the growth of the MoTe2 thin films free of any secondary phase. And the effect of other postdeposition treatments on the film characteristics was also investigated.

  5. Calculation of 3D genome structures for comparison of chromosome conformation capture experiments with microscopy: An evaluation of single-cell Hi-C protocols.

    Science.gov (United States)

    Lando, David; Stevens, Tim J; Basu, Srinjan; Laue, Ernest D

    2018-01-01

    Single-cell chromosome conformation capture approaches are revealing the extent of cell-to-cell variability in the organization and packaging of genomes. These single-cell methods, unlike their multi-cell counterparts, allow straightforward computation of realistic chromosome conformations that may be compared and combined with other, independent, techniques to study 3D structure. Here we discuss how single-cell Hi-C and subsequent 3D genome structure determination allows comparison with data from microscopy. We then carry out a systematic evaluation of recently published single-cell Hi-C datasets to establish a computational approach for the evaluation of single-cell Hi-C protocols. We show that the calculation of genome structures provides a useful tool for assessing the quality of single-cell Hi-C data because it requires a self-consistent network of interactions, relating to the underlying 3D conformation, with few errors, as well as sufficient longer-range cis- and trans-chromosomal contacts.

  6. Logarithmic conformal field theory through nilpotent conformal dimensions

    International Nuclear Information System (INIS)

    Moghimi-Araghi, S.; Rouhani, S.; Saadat, M.

    2001-01-01

    We study logarithmic conformal field theories (LCFTs) through the introduction of nilpotent conformal weights. Using this device, we derive the properties of LCFTs such as the transformation laws, singular vectors and the structure of correlation functions. We discuss the emergence of an extra energy momentum tensor, which is the logarithmic partner of the energy momentum tensor

  7. Structural stability, dynamical stability, thermoelectric properties, and elastic properties of GeTe at high pressure

    Science.gov (United States)

    Kagdada, Hardik L.; Jha, Prafulla K.; Śpiewak, Piotr; Kurzydłowski, Krzysztof J.

    2018-04-01

    The stability of GeTe in rhombohedral (R 3 m ), face centred cubic (F m 3 m ), and simple cubic (P m 3 m ) phases has been studied using density functional perturbation theory. The rhombohedral phase of GeTe is dynamically stable at 0 GPa, while F m 3 m and P m 3 m phases are stable at 3.1 and 33 GPa, respectively. The pressure-dependent phonon modes are observed in F m 3 m and P m 3 m phases at Γ and M points, respectively. The electronic and the thermoelectric properties have been investigated for the stable phases of GeTe. The electronic band gap for rhombohedral and F m 3 m phases of GeTe has been observed as 0.66 and 0.17 eV, respectively, while the P m 3 m phase shows metallic behavior. We have used the Boltzmann transport equation under a rigid band approximation and constant relaxation time approximation as implemented in boltztrap code for the calculation of thermoelectric properties of GeTe. The metallic behavior of P m 3 m phase gives a very low value of Seebeck coefficient compared to the other two phases as a function of temperature and the chemical potential μ. It is observed that the rhombohedral phase of GeTe exhibits higher thermoelectric performance. Due to the metallic nature of P m 3 m phase, negligible thermoelectric performance is observed compared to R 3 m and F m 3 m -GeTe. The calculated lattice thermal conductivities are low for F m 3 m -GeTe and high for R 3 m -GeTe. At the relatively higher temperature of 1350 K, the figure of merit ZT is found to be 0.7 for rhombohedral GeTe. The elastic constants satisfy the Born stability criteria for all three phases. The rhombohedral and F m 3 m phases exhibits brittleness and the P m 3 m phase shows ductile nature.

  8. First-principles calculation of the structural stability of 6d transition metals

    International Nuclear Information System (INIS)

    Oestlin, A.; Vitos, L.

    2011-01-01

    The phase stability of the 6d transition metals (elements 103-111) is investigated using first-principles electronic-structure calculations. Comparison with the lighter transition metals reveals that the structural sequence trend is broken at the end of the 6d series. To account for this anomalous behavior, the effect of relativity on the lattice stability is scrutinized, taking different approximations into consideration. It is found that the mass-velocity and Darwin terms give important contributions to the electronic structure, leading to changes in the interstitial charge density and, thus, in the structural energy difference.

  9. Conformality lost

    International Nuclear Information System (INIS)

    Kaplan, David B.; Lee, Jong-Wan; Son, Dam T.; Stephanov, Mikhail A.

    2009-01-01

    We consider zero-temperature transitions from conformal to nonconformal phases in quantum theories. We argue that there are three generic mechanisms for the loss of conformality in any number of dimensions: (i) fixed point goes to zero coupling, (ii) fixed point runs off to infinite coupling, or (iii) an IR fixed point annihilates with a UV fixed point and they both disappear into the complex plane. We give both relativistic and nonrelativistic examples of the last case in various dimensions and show that the critical behavior of the mass gap behaves similarly to the correlation length in the finite temperature Berezinskii-Kosterlitz-Thouless (BKT) phase transition in two dimensions, ξ∼exp(c/|T-T c | 1/2 ). We speculate that the chiral phase transition in QCD at large number of fermion flavors belongs to this universality class, and attempt to identify the UV fixed point that annihilates with the Banks-Zaks fixed point at the lower end of the conformal window.

  10. Structure and Mechanical Properties of Al-Cu-Fe-X Alloys with Excellent Thermal Stability

    Directory of Open Access Journals (Sweden)

    Andrea Školáková

    2017-11-01

    Full Text Available In this work, the structure and mechanical properties of innovative Al-Cu-Fe based alloys were studied. We focused on preparation and characterization of rapidly solidified and hot extruded Al-Cu-Fe, Al-Cu-Fe-Ni and Al-Cu-Fe-Cr alloys. The content of transition metals affects mechanical properties and structure. For this reason, microstructure, phase composition, hardness and thermal stability have been investigated in this study. The results showed exceptional thermal stability of these alloys and very good values of mechanical properties. Alloying by chromium ensured the highest thermal stability, while nickel addition refined the structure of the consolidated alloy. High thermal stability of all tested alloys was described in context with the transformation of the quasicrystalline phases to other types of intermetallics.

  11. Structure and Mechanical Properties of Al-Cu-Fe-X Alloys with Excellent Thermal Stability.

    Science.gov (United States)

    Školáková, Andrea; Novák, Pavel; Mejzlíková, Lucie; Průša, Filip; Salvetr, Pavel; Vojtěch, Dalibor

    2017-11-05

    In this work, the structure and mechanical properties of innovative Al-Cu-Fe based alloys were studied. We focused on preparation and characterization of rapidly solidified and hot extruded Al-Cu-Fe, Al-Cu-Fe-Ni and Al-Cu-Fe-Cr alloys. The content of transition metals affects mechanical properties and structure. For this reason, microstructure, phase composition, hardness and thermal stability have been investigated in this study. The results showed exceptional thermal stability of these alloys and very good values of mechanical properties. Alloying by chromium ensured the highest thermal stability, while nickel addition refined the structure of the consolidated alloy. High thermal stability of all tested alloys was described in context with the transformation of the quasicrystalline phases to other types of intermetallics.

  12. Structural and conformational variants of human beta2-microglobulin characterized by capillary electrophoresis and complementary separation methods

    DEFF Research Database (Denmark)

    Heegaard, Niels H H; Rovatti, Luca; Nissen, Mogens H

    2003-01-01

    The small (Mr = 11729) serum protein beta2-microglobulin is prone to precipitate as amyloid in a protein conformational disorder (PCD) that occurs in a significant number of patients on chronic hemodialysis. Analyses by capillary electrophoresis (CE) were undertaken to study beta2-microglobulin...

  13. Conformational analysis of gramicidin-gramicidin interactions at the air/water interface suggests that gramicidin aggregates into tube-like structures similar as found in the gramicidin-induced hexagonal HII phase

    NARCIS (Netherlands)

    Brasserua, R.; Killian, J.A.; Kruijff, B. de; Ruysschaert, J.M.

    1987-01-01

    The energetics of interaction and the type of aggregate structure in lateral assemblies of up to five gramicidin molecules in the β6.3 helical conformation at the air/water interface was calculated using conformational analysis procedures. It was found that within the aggregate two types of

  14. Structural and magnetic stability of Fe2NiSi

    International Nuclear Information System (INIS)

    Gupta, Dinesh C.; Bhat, Idris Hamid; Chauhan, Mamta

    2014-01-01

    Full-potential ab-initio calculations in the stable F-43m phase have been performed to investigate the structural and magnetic properties of Fe 2 NiSi inverse Heusler alloys. The spin magnetic moment distributions show that present material is ferromagnetic in stable F-43m phase. Further, spin resolved electronic structure calculations show that the discrepancy in magnetic moments of Fe-I and Fe-II depend upon the hybridization of Fe with the main group element. It is found that the main group electron concentration is predominantly responsible in establishing the magnetic properties, formation of magnetic moments and the magnetic order for present alloy

  15. Stability of Ruddlesden-Popper-structured oxides in humid conditions

    Science.gov (United States)

    Lehtimäki, M.; Yamauchi, H.; Karppinen, M.

    2013-08-01

    Some of layered transition-metal oxides are known to react with atmospheric humidity to form through topotactic intercalation reactions new water-containing layered structures. Here we investigate the influence of oxygen content (7-δ) of the Ruddlesden-Popper-structured Sr3FeMO7-δ (M=Ni, Mn, Ti) oxides on the water-intercalation reaction. It is found that their oxygen contents influence greatly the reactivity of the phases with water. Other factors possibly affecting the reactivity are discussed on the basis of the present data in combination with a comprehensive review of previous works on Ruddlesden-Popper and related layered oxide phases.

  16. Nash Stability in Additively Separable Hedonic Games and Community Structures

    DEFF Research Database (Denmark)

    Olsen, Martin

    2009-01-01

      We prove that the problem of deciding whether a Nash stable   partition exists in an Additively Separable Hedonic Game is   NP-complete. We also show that the problem of deciding whether a   non trivial Nash stable partition exists in an   Additively Separable Hedonic Game with   non......-negative and symmetric   preferences is NP-complete. We motivate our study of the   computational complexity by linking Nash stable partitions in   Additively Separable Hedonic Games to community structures in   networks. Our results formally justify that computing community   structures in general is hard....

  17. The stability and dynamic behaviour of fluid-loaded structures

    CSIR Research Space (South Africa)

    Suliman, Ridhwaan

    2015-07-01

    Full Text Available The deformation of slender elastic structures due to the bulk motion of fluid around it is a common multiphysics problem encountered in many applications. In this work we implement two computational FSI approaches in a partitioned manner: a finite...

  18. Factor Structure, Stability, and Congruence in the Functional Movement Screen

    Science.gov (United States)

    Kelleher, Leila K.; Beach, Tyson A. C.; Frost, David M.; Johnson, Andrew M.; Dickey, James P.

    2018-01-01

    The scoring scheme for the functional movement screen implicitly assumes that the factor structure is consistent, stable, and congruent across different populations. To determine if this is the case, we compared principal components analyses of three samples: a healthy, general population (n = 100), a group of varsity athletes (n = 101), and a…

  19. Global stability-based design optimization of truss structures using ...

    Indian Academy of Sciences (India)

    Furthermore, a pure pareto-ranking based multi-objective optimization model is employed for the design optimization of the truss structure with multiple objectives. The computational performance of the optimization model is increased by implementing an island model into its evolutionary search mechanism. The proposed ...

  20. Type of disturbance and ecological history determine structural stability.

    NARCIS (Netherlands)

    van der Wurff, A.W.G.; Kools, S.A.E.; Boivin, M.E.; van den Brink, P.J.; van den Megen, H.H.M.; Riksen, J.A.G.; Doroszuk, A.; Kammenga, J.E.

    2007-01-01

    This study aims to reveal whether complexity, namely, community and trophic structure, of chronically stressed soil systems is at increased risk or remains stable when confronted with a subsequent disturbance. Therefore, we focused on a grassland with a history of four centuries of patchy

  1. Type of disturbance and ecological history determine structural stability

    NARCIS (Netherlands)

    Wurff, van der A.W.G.; Kools, S.A.E.; Boivin, M.E.Y.; Brink, van den P.J.; Megen, van H.H.B.; Riksen, J.A.G.; Doroszuk, A.; Kammenga, J.E.

    2007-01-01

    This study aims to reveal whether complexity, namely, community and trophic structure, of chronically stressed soil systems is at increased risk or remains stable when confronted with a subsequent disturbance. Therefore, we focused on a grassland with a history of four centuries of patchy

  2. STABILIZATION OF A FAILED SLOPE WITH PILED STRUCTURES

    Directory of Open Access Journals (Sweden)

    M. Rifat KAHYAOĞLU

    2008-01-01

    Full Text Available Neogene aged units of a densely populated region of Western Turkey along the Aegean Sea coastline is susceptible to landslides causing frequent economic loss especially following raining seasons. Several landslides took place in the area covering a narrow band of the coastline between Izmir and Söke (Aydın. Countermeasures against these relatively small-scale slope failures in the region often involve construction of either reinforced concrete retaining walls or stabilizing piles, which can be easily constructed by local contractors. In this study borings, in-situ and laboratory soil mechanics tests, geophysical and geological investigations have been performed in order to investigate the landslide occurred in the yard of an elementary school in Söke township. The analysis of two rows of piled retaining system constructed to reuse the school building against a potential slides are presented. Three inclinometer measurements have been performed after completion of the bored pile system. It has been concluded that the measured and the calculated displacement values are both small. There is no problem of the built project by means of moments and displacements.

  3. Relativistic structure, stability, and gravitational collapse of charged neutron stars

    International Nuclear Information System (INIS)

    Ghezzi, Cristian R.

    2005-01-01

    Charged stars have the potential of becoming charged black holes or even naked singularities. We present a set of numerical solutions of the Tolman-Oppenheimer-Volkov equations that represents spherical charged compact stars in hydrostatic equilibrium. The stellar models obtained are evolved forward in time integrating the Einstein-Maxwell field equations. We assume an equation of state of a neutron gas at zero temperature. The charge distribution is taken as being proportional to the rest mass density distribution. The set of solutions present an unstable branch, even with charge-to-mass ratios arbitrarily close to the extremum case. We perform a direct check of the stability of the solutions under strong perturbations and for different values of the charge-to-mass ratio. The stars that are in the stable branch oscillate and do not collapse, while models in the unstable branch collapse directly to form black holes. Stars with a charge greater than or equal to the extreme value explode. When a charged star is suddenly discharged, it does not necessarily collapse to form a black hole. A nonlinear effect that gives rise to the formation of a shell of matter (in supermassive stars), is negligible in the present simulations. The results are in agreement with the third law of black hole thermodynamics and with the cosmic censorship conjecture

  4. Conformational plasticity of the coiled-coil domain of BmrR is required for bmr operator binding: the structure of unliganded BmrR.

    Science.gov (United States)

    Kumaraswami, Muthiah; Newberry, Kate J; Brennan, Richard G

    2010-04-30

    The multidrug-binding transcription regulator BmrR from Bacillus subtilis is a MerR family member that binds to a wide array of cationic lipophilic toxins to activate the transcription of the multidrug efflux pump gene bmr. Transcription activation from the sigma(A)-dependent bmr operator requires BmrR to remodel the nonoptimal 19-bp spacer between the -10 promoter element and the -35 promoter element in order to facilitate productive RNA polymerase binding. Despite the availability of several structures of BmrR bound to DNA and drugs, the lack of a BmrR structure in its unliganded or apo (DNA free and drug free) state hinders our full understanding of the structural transitions required for DNA binding and transcription activation. Here, we report the crystal structure of the constitutively active, unliganded BmrR mutant BmrR(E253Q/R275E). Superposition of the ligand-free (apo BmrR(E253Q/R275E)) and DNA-bound BmrR structures reveals that apo BmrR must undergo significant rearrangement in order to assume the DNA-bound conformation, including an outward rotation of minor groove binding wings, an inward movement of helix-turn-helix motifs, and a downward relocation of pliable coiled-coil helices. Computational analysis of the DNA-free and DNA-bound structures reveals a flexible joint that is located at the center of the coiled-coil helices. This region, which is composed of residues 94 through 98, overlaps the helical bulge that is observed only in the apo BmrR structure. This conformational hinge is likely common to other MerR family members with large effector-binding domains, but appears to be missing from the smaller metal-binding MerR family members. Interestingly, the center-to-center distance of the recognition helices of apo BmrR is 34 A and suggests that the conformational change from the apo BmrR structure to the bmr operator-bound BmrR structure is initiated by the binding of this transcription activator to a more B-DNA-like conformation. (c) 2010 Elsevier

  5. Raman study of CaDNA films as a function of water content and excess CaCl2 concentration: Stability of the B conformation.

    Science.gov (United States)

    Schwenker, Megan; Marlowe, Robert; Lee, Scott; Rupprecht, Allan

    2006-03-01

    Highly oriented, wet-spun films of CaDNA expand in the direction perpendicular to the helical axis as the hydration of the film is increased. CaDNA films with a high CaCl2 content show an unexpected shrinkage at a relative humidity of about 93%. We have performed Raman experiments on CaDNA films as a function of both water content and excess CaCl2 concentration in order to determine if this unexpected shrinkage might be related to a conformational transition of the DNA molecules. We find that the DNA molecules remain in the B conformation for all salt contents down to a relative humidity of 59%.

  6. Correlation between local structure and stability of supercooled liquid state in Zr-based metallic glasses

    International Nuclear Information System (INIS)

    Saida, Junji; Imafuku, Muneyuki; Sato, Shigeo; Sanada, Takashi; Matsubara, Eiichiro; Inoue, Akihisa

    2007-01-01

    The correlation between the local structure and stability of supercooled liquid state is investigated in the Zr 70 (Ni, Cu) 30 binary and Zr 70 Al 10 (Ni, Cu) 20 (numbers indicate at.%) ternary metallic glasses. The Zr 70 Ni 30 binary amorphous alloy with a low stability of supercooled liquid state has a tetragonal Zr 2 Ni-like local structure around Ni atom. Meanwhile, the Zr 70 Cu 30 binary metallic glass has a different local structure of tetragonal Zr 2 Cu, where we suggest the icosahedral local structure by the quasicrystallization behavior in addition of a very small amount of noble metals. The effect of Al addition on the local structure in the Zr-Ni alloy is also examined. We have investigated that the dominant local structure changes in the icosahedral-like structure from the tetragonal Zr 2 Ni-like local structure by the Al substitution with Ni accompanying with the significant stabilization of supercooled liquid state. It is concluded that the formation of icosahedral local structure contributes to the enhancement of stability of supercooled liquid state in the Zr-based alloys

  7. The effect of relativity on stability of Copernicium phases, their electronic structure and mechanical properties

    Science.gov (United States)

    Čenčariková, Hana; Legut, Dominik

    2018-05-01

    The phase stability of the various crystalline structures of the super-heavy element Copernicium was determined based on the first-principles calculations with different levels of the relativistic effects. We utilized the Darwin term, mass-velocity, and spin-orbit interaction with the single electron framework of the density functional theory while treating the exchange and correlation effects using local density approximations. It is found that the spin-orbit coupling is the key component to stabilize the body-centered cubic (bcc) structure over the hexagonal closed packed (hcp) structure, which is in accord with Sol. Stat. Comm. 152 (2012) 530, but in contrast to Atta-Fynn and Ray (2015) [11], Gaston et al. (2007) [10], Papaconstantopoulos (2015) [9]. It seems that the main role here is the correct description of the semi-core relativistic 6p1/2 orbitals. The all other investigated structures, i.e. face-centered cubic (fcc) , simple cubic (sc) as well as rhombohedral (rh) structures are higher in energy. The criteria of mechanical stability were investigated based on the calculated elastic constants, identifying the phase instability of fcc and rh structures, but surprisingly confirm the stability of the energetically higher sc structure. In addition, the pressure-induced structural transition between two stable sc and bcc phases has been detected. The ground-state bcc structure exhibits the highest elastic anisotropy from single elements of the Periodic table. At last, we support the experimental findings that Copernicium is a metal.

  8. Algebraic conformal field theory

    International Nuclear Information System (INIS)

    Fuchs, J.; Nationaal Inst. voor Kernfysica en Hoge-Energiefysica

    1991-11-01

    Many conformal field theory features are special versions of structures which are present in arbitrary 2-dimensional quantum field theories. So it makes sense to describe 2-dimensional conformal field theories in context of algebraic theory of superselection sectors. While most of the results of the algebraic theory are rather abstract, conformal field theories offer the possibility to work out many formulae explicitly. In particular, one can construct the full algebra A-bar of global observables and the endomorphisms of A-bar which represent the superselection sectors. Some explicit results are presented for the level 1 so(N) WZW theories; the algebra A-bar is found to be the enveloping algebra of a Lie algebra L-bar which is an extension of the chiral symmetry algebra of the WZW theory. (author). 21 refs., 6 figs

  9. Effect of secondary structure on the potential of mean force for poly-L-lysine in the alpha-Helix and beta-sheet conformations

    Energy Technology Data Exchange (ETDEWEB)

    Grigsby, J.J.; Blanch, H.W.; Prausnitz, J.M.

    2001-10-30

    Because poly-L-lysine (PLL) can exist in the {alpha}-helix or {beta}-sheet conformation depending on solution preparation and solution conditions, PLL is a suitable candidate to probe the dependence of protein interactions on secondary structure. The osmotic second virial coefficient and weight-average molecular weight are reported from low-angle laser-light scattering measurements for PLL as a function of NaCl concentration, pH, and {alpha}-helix or {beta}-sheet content. Interactions between PLL molecules become more attractive as salt concentration increases due to screening of PLL charge by salt ions and at low salt concentration become more attractive as pH increases due to decreased net charge on PLL. The experimental results show that interactions are stronger for the {beta}-sheet conformation than for the {alpha}-helix conformation. A spherically-symmetric model for the potential of mean force is used to account for specific interactions not described by DLVO theory and to show how differences in secondary structure affect PLL interactions.

  10. Structure and stability of BaTiSi₂O₇.

    Science.gov (United States)

    Viani, Alberto; Palermo, Andrea; Zanardi, Stefano; Demitri, Nicola; Petrícek, Václav; Varini, Federico; Belluso, Elena; Ståhl, Kenny; Gualtieri, Alessandro Francesco

    2015-04-01

    Due to their optical, photo-luminescence (PL), and afterglow properties, barium titanosilicates are compounds of great interest for functional materials and light-emitting devices. Among them, BaTiSi2O7 (BTS2) is certainly one of the most intriguing; it displays peculiar properties (e.g. PL orange emission) whose exhaustive explanation has been hampered to date by the lack of a structure model. In this work, BTS2 and the related compound BaTiSi4O11 (BTS4) were synthesized through conventional solid-state reaction methods. BTS2 invariably shows complex twinning patterns. Thus, its structure solution and Rietveld structure refinement were attempted using synchrotron powder diffraction. BTS2 was found to be an intergrowth of monoclinic and triclinic crystals. The monoclinic phase has the space group P21/n and unit cell a = 7.9836 (3), b = 10.0084 (4), c = 7.4795 (3) Å, and β = 100.321 (3)°, whereas the triclinic phase has the space group P\\bar 1 and unit cell a = 7.99385 (4), b = 10.01017 (5), c = 7.47514 (3) Å, α = 90.084 (8), β = 100.368 (8) and γ = 89.937 (9)°. These lattices can be seen as a distortion of that of tetragonal synthetic β-BaVSi2O7 with Ti in place of V. The structure models obtained from this study confirm the presence of fivefold coordinated Ti atoms in a distorted pyramidal configuration. The proposed solution supports existing theories for the explanation of the PL orange colour in BTS2.

  11. Structural Integrity and Hydraulic Stability of Dolos Armour Layers

    DEFF Research Database (Denmark)

    Burcharth, H. F.

    A method for development of design diagrams to ensure structural integrity of slender unreinforced concrete breakwater armour units is presented. The method is based on experimental data from small scale flume tests as well as impact loading of prototype and small scale units. A prerequisite......-parameter characterization makes it possible to develop simple design diagrams for engineering purposes. Specific design diagrams for integrity of Dolos armour units with the waist ratio as a variable have been produced....

  12. A combined variable temperature 600 MHz NMR/MD study of the calcium release agent cyclic adenosine diphosphate ribose (cADPR): Structure, conformational analysis, and thermodynamics of the conformational equilibria.

    Science.gov (United States)

    Javornik, Uroš; Plavec, Janez; Wang, Baifan; Graham, Steven M

    2018-01-02

    A combined variable temperature 600 MHz NMR/molecular dynamics study of the Ca 2+ -release agent cyclic adenosine 5'-diphosphate ribose (cADPR) was conducted. In addition to elucidating the major and minor orientations of the conformationally flexible furanose rings, γ- (C4'-C5'), and β- (C5'-O5') bonds, the thermodynamics (ΔH o , ΔS o ) associated with each of these conformational equilibria were determined. Both furanose rings were biased towards a south conformation (64-74%) and both β-bonds heavily favored trans conformations. The R-ring γ-bond was found to exist almost exclusively as the γ + conformer, whereas the A-ring γ-bond was a mixture of the γ + and γ t conformers, with the trans conformer being slightly favored. Enthalpic factors accounted for most of the observed conformational preferences, although the R-ring furanose exists as its major conformation based solely on entropic factors. There was excellent agreement between the NMR and MD results, particularly with regard to the conformer identities, but the MD showed a bias towards γ + conformers. The MD results showed that both N-glycosidic χ-bonds are exclusively syn. Collectively the data allowed for the construction of a model for cADPR in which many of the conformationally flexible units in fact effectively adopt single orientations and where most of the conformational diversity resides in its A-ring furanose and γ-bond. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Structure stability index allocation theory and measurement of laser prototype facility

    International Nuclear Information System (INIS)

    Zhang Junwei; China Academy of Engineering Physics, Mianyang; Zhou Hai; Feng Bin; Lin Donghui; Jing Feng; Zhou Yi; Wang Shilong

    2008-01-01

    Structure stability is an important design index of ICF driver. Based on laser prototype facility(TIL) design characteristic of multi-pass amplifier and frame structure, the optical matrix is used to analyze the single optical element influence on the beam drift and get the mathematic model. Considering all the optical elements influence on the beam drift, the mathematic model of the optical element stability index allocation is built, the parameter relation of the mathematic model is defined according to the structure characteristic of TIL, the stability index of each optical element is got as the support structure design index. Charge-coupled device(CCD) detect technology is used to measure the general beam stability of TIL. The root mean square beam drift in x and y direction are 2.78 μm, the difference between peak and valley values are 14.4 μm and 15.60 μm, respectively. The result indicates that the stability drift of the prototype facility can satisfy the design requirement, the way of the stability allocation is reasonable. (authors)

  14. Range and stability of structural colors generated by Morpho-inspired color reflectors.

    Science.gov (United States)

    Chung, Kyungjae; Shin, Jung H

    2013-05-01

    The range and stability of structural colors generated by Morpho-inspired color reflectors are investigated. We find that despite the internal randomness of such structures that gives rise to their Morpho-like angle-independent iridescence, their colors under ambient lighting condition can be predicted by simple transfer-matrix calculations of corresponding planar multilayer structures. By calculating the possible range of colors generated by multilayers of different structures and material combinations using such transfer-matrix methods, we find that low-refractive index multilayers with intrastructure absorption, such as the melanin-containing chitin/air multilayer structure from the Morpho butterflies, can provide not only the most pure structural colors with the largest color gamut, but also the highest stability of color against variations in multilayer structure.

  15. Crystal structure of the thioesterification conformation of Bacillus subtilis o-succinylbenzoyl-CoA synthetase reveals a distinct substrate-binding mode.

    Science.gov (United States)

    Chen, Yaozong; Li, Tin Lok; Lin, Xingbang; Li, Xin; Li, Xiang David; Guo, Zhihong

    2017-07-21

    o -Succinylbenzoyl-CoA (OSB-CoA) synthetase (MenE) is an essential enzyme in bacterial vitamin K biosynthesis and an important target in the development of new antibiotics. It is a member of the adenylating enzymes (ANL) family, which reconfigure their active site in two different active conformations, one for the adenylation half-reaction and the other for a thioesterification half-reaction, in a domain-alternation catalytic mechanism. Although several aspects of the adenylating mechanism in MenE have recently been uncovered, its thioesterification conformation remains elusive. Here, using a catalytically competent Bacillus subtilis mutant protein complexed with an OSB-CoA analogue, we determined MenE high-resolution structures to 1.76 and 1.90 Å resolution in a thioester-forming conformation. By comparison with the adenylation conformation, we found that MenE's C-domain rotates around the Ser-384 hinge by 139.5° during domain-alternation catalysis. The structures also revealed a thioesterification active site specifically conserved among MenE orthologues and a substrate-binding mode distinct from those of many other acyl/aryl-CoA synthetases. Of note, using site-directed mutagenesis, we identified several residues that specifically contribute to the thioesterification half-reaction without affecting the adenylation half-reaction. Moreover, we observed a substantial movement of the activated succinyl group in the thioesterification half-reaction. These findings provide new insights into the domain-alternation catalysis of a bacterial enzyme essential for vitamin K biosynthesis and of its adenylating homologues in the ANL enzyme family. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Structural basis of thermal stability of the tungsten cofactor synthesis protein MoaB from Pyrococcus furiosus.

    Directory of Open Access Journals (Sweden)

    Nastassia Havarushka

    Full Text Available Molybdenum and tungsten cofactors share a similar pterin-based scaffold, which hosts an ene-dithiolate function being essential for the coordination of either molybdenum or tungsten. The biosynthesis of both cofactors involves a multistep pathway, which ends with the activation of the metal binding pterin (MPT by adenylylation before the respective metal is incorporated. In the hyperthermophilic organism Pyrococcus furiosus, the hexameric protein MoaB (PfuMoaB has been shown to catalyse MPT-adenylylation. Here we determined the crystal structure of PfuMoaB at 2.5 Å resolution and identified key residues of α3-helix mediating hexamer formation. Given that PfuMoaB homologues from mesophilic organisms form trimers, we investigated the impact on PfuMoaB hexamerization on thermal stability and activity. Using structure-guided mutagenesis, we successfully disrupted the hexamer interface in PfuMoaB. The resulting PfuMoaB-H3 variant formed monomers, dimers and trimers as determined by size exclusion chromatography. Circular dichroism spectroscopy as well as chemical cross-linking coupled to mass spectrometry confirmed a wild-type-like fold of the protomers as well as inter-subunits contacts. The melting temperature of PfuMoaB-H3 was found to be reduced by more than 15 °C as determined by differential scanning calorimetry, thus demonstrating hexamerization as key determinant for PfuMoaB thermal stability. Remarkably, while a loss of activity at temperatures higher than 50 °C was observed in the PfuMoaB-H3 variant, at lower temperatures, we determined a significantly increased catalytic activity. The latter suggests a gain in conformational flexibility caused by the disruption of the hexamerization interface.

  17. Oxidative stability during storage of structured lipids produced from fish oil and caprylic acid

    DEFF Research Database (Denmark)

    Nielsen, Nina Skall; Xu, Xuebing; Timm Heinrich, Maike

    2004-01-01

    Structured lipids produced by enzymatic or chemical methods for different applications have been receiving considerable attention. The oxidative stability of a randomized structured lipid (RFO), produced by chemical interesterification from fish oil (FO) and tricaprylin, and a specific structured...... lipid (SFO), produced by enzymatic interesterification from the same oil and caprylic acid, was compared with the stability of FO. Oils were stored at 2degreesC for 11 wk followed by storage at 20degreesC for 6 wk. In addition, the antioxidative effect of adding the metal chelators EDTA or citric acid...

  18. Effects of PEG size on structure, function and stability of PEGylated BSA

    DEFF Research Database (Denmark)

    Plesner, Bitten; Fee, Conan J.; Westh, Peter

    2011-01-01

    The effects of PEGylation on the structural, thermal and functional stability of bovine serum albumin (BSA) were investigated using BSA and 6 linear mono-PEGylated BSA compounds. The secondary and tertiary structure of BSA measured by circular dichroism (CD) was independent of PEGylation. In cont...

  19. Structural properties and out-of-plane stability of roller bent steel arches

    NARCIS (Netherlands)

    Spoorenberg, R.C.

    2011-01-01

    In contemporary architecture the use of steel arches has seen a significant increase. They are applied in buildings and large span bridges, combining structural design with architectural merits. For arches lacking lateral support (or freestanding arches) the out-of-plane structural stability

  20. Stability of Ruddlesden–Popper-structured oxides in humid conditions

    International Nuclear Information System (INIS)

    Lehtimäki, M.; Yamauchi, H.; Karppinen, M.

    2013-01-01

    Some of layered transition-metal oxides are known to react with atmospheric humidity to form through topotactic intercalation reactions new water-containing layered structures. Here we investigate the influence of oxygen content (7−δ) of the Ruddlesden–Popper-structured Sr 3 FeMO 7−δ (M=Ni, Mn, Ti) oxides on the water-intercalation reaction. It is found that their oxygen contents influence greatly the reactivity of the phases with water. Other factors possibly affecting the reactivity are discussed on the basis of the present data in combination with a comprehensive review of previous works on Ruddlesden–Popper and related layered oxide phases. - Graphical abstract: Many of the Ruddlesden–Popper-structured A 3 B 2 O 7−δ oxides readily react with water via intercalation reactions. Three possible factors affecting the water intercalation are identified: oxygen content of the phase, ionic radius of cation A and valence state of cation B. The resultant layered water-derivative phases can be categorised into two groups, depending on the crystal symmetry of the phase. Highlights: • Ruddlesden–Popper oxides A 3 B 2 O 7−δ often accommodate water via intercalation reaction. • The lower the oxygen content 7−δ is the more readily the intercalation reaction occurs. • The second factor promoting the reaction is the large size of cation A. • The third possible factor is the high valence state of cation B. • Resultant water-derivatives can be categorised into two groups depending on symmetry

  1. Stability of Ruddlesden–Popper-structured oxides in humid conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lehtimäki, M.; Yamauchi, H.; Karppinen, M., E-mail: maarit.karppinen@aalto.fi

    2013-08-15

    Some of layered transition-metal oxides are known to react with atmospheric humidity to form through topotactic intercalation reactions new water-containing layered structures. Here we investigate the influence of oxygen content (7−δ) of the Ruddlesden–Popper-structured Sr{sub 3}FeMO{sub 7−δ} (M=Ni, Mn, Ti) oxides on the water-intercalation reaction. It is found that their oxygen contents influence greatly the reactivity of the phases with water. Other factors possibly affecting the reactivity are discussed on the basis of the present data in combination with a comprehensive review of previous works on Ruddlesden–Popper and related layered oxide phases. - Graphical abstract: Many of the Ruddlesden–Popper-structured A{sub 3}B{sub 2}O{sub 7−δ} oxides readily react with water via intercalation reactions. Three possible factors affecting the water intercalation are identified: oxygen content of the phase, ionic radius of cation A and valence state of cation B. The resultant layered water-derivative phases can be categorised into two groups, depending on the crystal symmetry of the phase. Highlights: • Ruddlesden–Popper oxides A{sub 3}B{sub 2}O{sub 7−δ} often accommodate water via intercalation reaction. • The lower the oxygen content 7−δ is the more readily the intercalation reaction occurs. • The second factor promoting the reaction is the large size of cation A. • The third possible factor is the high valence state of cation B. • Resultant water-derivatives can be categorised into two groups depending on symmetry.

  2. On dependence of stability of lanthanum complexes with aminopolycarboxylic acids on the complex structure

    International Nuclear Information System (INIS)

    Poluehktov, N.S.; Meshkova, S.B.; Danilkovich, M.M.; Topilova, Z.M.

    1985-01-01

    Regularities in changes of stability constants of lanthanum complexes with aminopolycarboxylic acids (APA) versus their structure are studied, The stability of lathanum-APA complexes depends mainly on the number of carboxyl groups in a ligand molecule. At that, the highest stability constant is characteristic of a complex with a ligand, containing 3 nitrogen atoms and 5 carboxyl groups, in the presenoe of which the lanthanum ion coordination sphere gets satupated. The oxyethy group introduction into a ligand molecule also improves the lanthanum complex stability but to a lesser degree than during the introduction of a carboxyl group. The number of nitrogen atoms in a ligand polecule affects insignificantly the complex stability constant value, and the elongation of a chain of CH 2 groups, separating nitrogen atoms, reduces the constant to a -0.6 power

  3. Dissecting the structure of surface stabilizer on the dispersion of inorganic nanoparticles in aqueous medium

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yong; Yu, Zongzhi; Zheng, Junping, E-mail: jpzheng@tju.edu.cn [Tianjin University, Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering (China)

    2017-03-15

    Dispersing inorganic nanoparticles in aqueous solutions is a key requirement for a great variety of products and processes, including carriers in drug delivery or fillers in polymers. To be highly functional in the final product, inorganic particles are required to be finely dispersed in nanoscale. In this study, silica was selected as a representative inorganic particle. Surface stabilizers with different chain length and charged group were designed to reveal the influence of electrostatic and van der Waals forces between silica and stabilizer on the dispersion of silica particles in aqueous medium. Results showed surface stabilizer with longer alkyl chain and charged group exerted best ability to deaggregate silica, leading to a hydrodynamic size of 51.1 nm. Surface stabilizer designing with rational structure is a promising solution for deagglomerating and reducing process time and energy. Giving the designability and adaptability of surface stabilizer, this method is of potential for dispersion of other inorganic nanoparticles.

  4. Dissecting the structure of surface stabilizer on the dispersion of inorganic nanoparticles in aqueous medium

    Science.gov (United States)

    Ding, Yong; Yu, Zongzhi; Zheng, Junping

    2017-03-01

    Dispersing inorganic nanoparticles in aqueous solutions is a key requirement for a great variety of products and processes, including carriers in drug delivery or fillers in polymers. To be highly functional in the final product, inorganic particles are required to be finely dispersed in nanoscale. In this study, silica was selected as a representative inorganic particle. Surface stabilizers with different chain length and charged group were designed to reveal the influence of electrostatic and van der Waals forces between silica and stabilizer on the dispersion of silica particles in aqueous medium. Results showed surface stabilizer with longer alkyl chain and charged group exerted best ability to deaggregate silica, leading to a hydrodynamic size of 51.1 nm. Surface stabilizer designing with rational structure is a promising solution for deagglomerating and reducing process time and energy. Giving the designability and adaptability of surface stabilizer, this method is of potential for dispersion of other inorganic nanoparticles.

  5. Trophic structure and community stability in an overfished ecosystem

    KAUST Repository

    Utne-Palm, Anne Christine

    2010-07-15

    Since the collapse of the pelagic fisheries off southwest Africa in the late 1960s, jellyfish biomass has increased and the structure of the Benguelan fish community has shifted, making the bearded goby (Sufflogobius bibarbatus) the new predominant prey species. Despite increased prédation pressure and a harsh environment, the gobies are thriving. Here we show that physiological adaptations and antipredator and foraging behaviors underpin the success of these fish. In particular, body-tissue isotope signatures reveal that gobies consume jellyfish and sulphidic diatomaceous mud, transferring "dead-end" resources back into the food chain.

  6. Trophic structure and community stability in an overfished ecosystem

    KAUST Repository

    Utne-Palm, Anne Christine; Salvanes, Anne Gro Vea; Currie, Bronwen; Kaartvedt, Stein; Nilsson, Gö ran E.; Braithwaite, Victoria A.; Stecyk, Jonathan A W; Hundt, Matthias; Van Der Bank, Megan G.; Flynn, Bradley A.; Sandvik, Guro Katrine; Klevjer, Thor Aleksander; Sweetman, Andrew K.; Brü chert, Volker; Pittman, Karin A.; Peard, Kathleen R.; Lunde, Ida Gjervold; Strandaba, R. A U; Gibbons, Mark J.

    2010-01-01

    Since the collapse of the pelagic fisheries off southwest Africa in the late 1960s, jellyfish biomass has increased and the structure of the Benguelan fish community has shifted, making the bearded goby (Sufflogobius bibarbatus) the new predominant prey species. Despite increased prédation pressure and a harsh environment, the gobies are thriving. Here we show that physiological adaptations and antipredator and foraging behaviors underpin the success of these fish. In particular, body-tissue isotope signatures reveal that gobies consume jellyfish and sulphidic diatomaceous mud, transferring "dead-end" resources back into the food chain.

  7. Solid state conformational classification of eight-membered rings

    DEFF Research Database (Denmark)

    Pérez, J.; García, L.; Kessler, M.

    2005-01-01

    A statistical classification of the solid state conformation in the title complexes using data retrieved from the Cambridge Structural Database (CSD) has been made. Phosphate and phosphinate complexes show a chair conformation preferably. In phosphonate complexes, the most frequent conformations...

  8. SU-E-T-346: Effect of Jaw Position On Dose to Critical Structures in 3-D Conformal Radiotherapy Treatment of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Paudel, N; Han, E; Liang, X; Morrill, S; Zhang, X; Hardee, M; Penagaricano, J; Ratanatharathorn, V [Vaneerat, University of Arkansas for Medical Sciences, Little Rock, AR (United States)

    2015-06-15

    Purpose: Three-dimensional conformal therapy remains a valid and widely used modality for pancreatic radiotherapy treatment. It usually meets dose constraints on critical structures. However, careful positioning of collimation jaws can reduce dose to the critical structures. Here we investigate the dosimetric effect of jaw position in MLC-based 3-D conformal treatment planning on critical structures. Methods: We retrospectively selected seven pancreatic cancer patients treated with 3-D conformal radiotherapy. We started with treatment plans (Varian Truebeam LINAC, Eclipse TPS, AAA, 18MV) having both x and y jaws aligned with the farthest extent of the block outline (8mm around PTV). Then we subsequently moved either both x-jaws or all x and y jaws outwards upto 3 cm in 1 cm increments and investigated their effect on average and maximum dose to neighboring critical structures keeping the same coverage to treatment volume. Results: Lateral displacement of both x-jaws by 1cm each increased kidney and spleen mean dose by as much as 1.7% and 1.3% respectively and superior inferior displacement increased liver, right kidney, stomach and spleen dose by as much as 2.1%, 2%, 5.2% and 1.6% respectively. Displacement of all x and y-jaws away by 1cm increased the mean dose to liver, right kidney, left kidney, bowels, cord, stomach and spleen by as much as 4.9%, 5.9%, 2.1%, 2.8%, 7.4%, 10.4% and 4.2% respectively. Percentage increase in mean dose due to 2 and 3cm jaw displacement increased almost linearly with the displaced distance. Changes in maximum dose were much smaller (mostly negligible) than the changes in mean dose. Conclusion: Collimation jaw position affects dose mostly to critical structures adjacent to it. Though treatment plans with MLCs conforming the block margin usually meet dose constraints to critical structures, keeping jaws all the way in, to the edge of the block reduces dose to the critical structures during radiation treatment.

  9. Contact angles of wetting and water stability of soil structure

    Science.gov (United States)

    Kholodov, V. A.; Yaroslavtseva, N. V.; Yashin, M. A.; Frid, A. S.; Lazarev, V. I.; Tyugai, Z. N.; Milanovskiy, E. Yu.

    2015-06-01

    From the soddy-podzolic soils and typical chernozems of different texture and land use, dry 3-1 mm aggregates were isolated and sieved in water. As a result, water-stable aggregates and water-unstable particles composing dry 3-1 mm aggregates were obtained. These preparations were ground, and contact angles of wetting were determined by the static sessile drop method. The angles varied from 11° to 85°. In most cases, the values of the angles for the water-stable aggregates significantly exceeded those for the water-unstable components. In terms of carbon content in structural units, there was no correlation between these parameters. When analyzing the soil varieties separately, the significant positive correlation between the carbon content and contact angle of aggregates was revealed only for the loamy-clayey typical chernozem. Based on the multivariate analysis of variance, the value of contact wetting angle was shown to be determined by the structural units belonging to water-stable or water-unstable components of macroaggregates and by the land use type. In addition, along with these parameters, the texture has an indirect effect.

  10. Swelling, Structure, and Phase Stability of Soft, Compressible Microgels

    Science.gov (United States)

    Denton, Alan R.; Urich, Matthew

    Microgels are soft colloidal particles that swell when dispersed in a solvent. The equilibrium particle size is governed by a delicate balance of osmotic pressures, which can be tuned by varying single-particle properties and externally controlled conditions, such as temperature, pH, ionic strength, and concentration. Because of their tunable size and ability to encapsulate dye or drug molecules, microgels have practical relevance for biosensing, drug delivery, carbon capture, and filtration. Using Monte Carlo simulation, we model suspensions of microgels that interact via Hertzian elastic interparticle forces and can expand or contract via trial size changes governed by the Flory-Rehner free energy of cross-linked polymer gels. We analyze the influence of particle compressibility and size fluctuations on bulk structural and thermal properties by computing swelling ratios, radial distribution functions, static structure factors, osmotic pressures, and freezing densities. With increasing density, microgels progressively deswell and their intrinsic polydispersity broadens, while compressibility acts to forestall crystallization. This work was supported by the National Science Foundation under Grant No. DMR- 1106331.

  11. Structure and stability of solid Xe(H2)n

    International Nuclear Information System (INIS)

    Somayazulu, Maddury; Hemley, Russell J.; Dera, Przemyslaw; Smith, Jesse

    2015-01-01

    Mixtures of xenon and molecular hydrogen form a series of hexagonal, van der Waals compounds at high pressures and at 300 K. Synchrotron, x-ray, single crystal diffraction studies reveal that below 7.5 GPa, Xe(H 2 ) 8 crystallizes in a P3 - m1 structure that displays pressure-induced occupancy changes of two pairs of xenon atoms located on the 2c and 2d sites (while the third pair on yet another 2c site remains fully occupied). The occupancy becomes 1 at the P3 - m1 to R3 transition and all the xenon atoms occupy the 3d sites in the high-pressure structure. These pressure-induced changes in occupancy coincide with volume changes that maintain the average Xe:H 2 stoichiometry fixed at 1:8. The synchrotron x-ray diffraction and Raman measurements show that this unique hydrogen-bearing compound that can be synthesized at 4.2 GPa and 300 K, quenched at low temperatures to atmospheric pressure, and retained up to 90 K on subsequent warming

  12. Monte Carlo analysis of critical phenomenon of the Ising model on memory stabilizer structures

    International Nuclear Information System (INIS)

    Viteri, C. Ricardo; Tomita, Yu; Brown, Kenneth R.

    2009-01-01

    We calculate the critical temperature of the Ising model on a set of graphs representing a concatenated three-bit error-correction code. The graphs are derived from the stabilizer formalism used in quantum error correction. The stabilizer for a subspace is defined as the group of Pauli operators whose eigenvalues are +1 on the subspace. The group can be generated by a subset of operators in the stabilizer, and the choice of generators determines the structure of the graph. The Wolff algorithm, together with the histogram method and finite-size scaling, is used to calculate both the critical temperature and the critical exponents of each structure. The simulations show that the choice of stabilizer generators, both the number and the geometry, has a large effect on the critical temperature.

  13. Functional and structural stability of the epidermal growth factor receptor in detergent micelles and phospholipid nanodiscs

    DEFF Research Database (Denmark)

    Mi, Li-Zhi; Grey, Michael J; Nishida, Noritaka

    2008-01-01

    Cellular signaling mediated by the epidermal growth factor receptor (EGFR or ErbB) family of receptor tyrosine kinases plays an important role in regulating normal and oncogenic cellular physiology. While structures of isolated EGFR extracellular domains and intracellular protein tyrosine kinase...... differential functional stability in Triton X-100 versus dodecyl maltoside. Furthermore, the kinase activity can be significantly stabilized by reconstituting purified EGF-bound EGFR dimers in phospholipid nanodiscs or vesicles, suggesting that the environment around the hydrophobic transmembrane...

  14. Thermodynamic Stability of Structure H Hydrates Based on the Molecular Properties of Large Guest Molecules

    OpenAIRE

    Tezuka, Kyoichi; Taguchi, Tatsuhiko; Alavi, Saman; Sum, Amadeu K.; Ohmura, Ryo

    2012-01-01

    This paper report analyses of thermodynamic stability of structure-H clathrate hydrates formed with methane and large guest molecules in terms of their gas phase molecular sizes and molar masses for the selection of a large guest molecule providing better hydrate stability. We investigated the correlation among the gas phase molecular sizes, the molar masses of large molecule guest substances, and the equilibrium pressures. The results suggest that there exists a molecular-size value for the ...

  15. 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...

  16. Compact conformations of human protein disulfide isomerase.

    Directory of Open Access Journals (Sweden)

    Shang Yang

    Full Text Available Protein disulfide isomerase (PDI composed of four thioredoxin-like domains a, b, b', and a', is a key enzyme catalyzing oxidative protein folding in the endoplasmic reticulum. Large scale molecular dynamics simulations starting from the crystal structures of human PDI (hPDI in the oxidized and reduced states were performed. The results indicate that hPDI adopts more compact conformations in solution than in the crystal structures, which are stabilized primarily by inter-domain interactions, including the salt bridges between domains a and b' observed for the first time. A prominent feature of the compact conformations is that the two catalytic domains a and a' can locate close enough for intra-molecular electron transfer, which was confirmed by the characterization of an intermediate with a disulfide between the two domains. Mutations, which disrupt the inter-domain interactions, lead to decreased reductase activity of hPDI. Our molecular dynamics simulations and biochemical experiments reveal the intrinsic conformational dynamics of hPDI and its biological impact.

  17. Structural Evolution and Stability of Sol-Gel Biocatalysts

    International Nuclear Information System (INIS)

    Rodgers, L.E.; Foster, L.J.R.; Holden, P.J.; Knott, R.B.; Bartlett, J.B.

    2005-01-01

    Full text: Immobilisation strategies for catalytic enzymes are important as they allow reuse of the biocatalysts. Sol-gel materials have been used to immobilise Candida antarctica lipase B (CALB), a commonly used industrial enzyme with a known crystal structure. The sol-gel bioencapsulate is produced through the condensation of suitable metal alkoxides in the presence of CALB, yielding materials with controlled pore sizes, volume and surface chemistry. Sol-gel matrices have been shown to prolong the catalytic life and enhance the activity of CALB, although the molecular basis for this effect has yet to be elucidated due to the limitations of analysis techniques applied to date. Small angle neutron scattering (SANS) allows such multicomponent systems to be characterised through contrast matching. In the sol-gel bioencapsulate system, at the contrast match point for silica, residual scattering intensity is due to the CALB and density fluctuations in the matrix. A SANS contrast variation series found the match point for the silica matrix, both with and without enzyme present, to be around 35 percent. The model presented here proposes a mechanism for the interaction between CALB and the surrounding sol-gel matrix, and the observed improvement in enzyme activity and matrix strength. The SANS protocol developed here may be applied more generally to bioencapsulates. (authors)

  18. Leaching of concrete : the leaching process : extrapolation of deterioration : effect on the structural stability

    OpenAIRE

    Fagerlund, Göran

    2000-01-01

    The leaching process when water attacks concrete, and the effect of leaching on the strength and durability of a concrete structure, is analysed theoretically. Technique for prediction of the future leaching and structural stability is outlined. The analysis is to a certain extent supported by data from literature. The leaching process is divided in five different types: 1: Pure surface leaching 2: Surface leaching involving erosion 3: Homogeneous leaching over the entire structure 4...

  19. Robust stability analysis of large power systems using the structured singular value theory

    Energy Technology Data Exchange (ETDEWEB)

    Castellanos, R.; Sarmiento, H. [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico); Messina, A.R. [Cinvestav, Graduate Program in Electrical Engineering, Guadalajara, Jalisco (Mexico)

    2005-07-01

    This paper examines the application of structured singular value (SSV) theory to analyse robust stability of complex power systems with respect to a set of structured uncertainties. Based on SSV theory and the frequency sweep method, techniques for robust analysis of large-scale power systems are developed. The main interest is focused on determining robust stability for varying operating conditions and uncertainties in the structure of the power system. The applicability of the proposed techniques is verified through simulation studies on a large-scale power system. In particular, results for the system are considered for a wide range of uncertainties of operating conditions. Specifically, the developed technique is used to estimate the effect of variations in the parameters of a major system inter-tie on the nominal stability of a critical inter-area mode. (Author)

  20. Non-Essential Activation of Co"2"+ and Zn"2"+ on Mushroom Tyrosinase: Kinetic and Structural Stability

    International Nuclear Information System (INIS)

    Gheibi, N.; Sarreshtehdari, M.; Saboury, A. A.

    2011-01-01

    Tyrosinase is a widespread enzyme with great promising capabilities. The Lineweaver-Burk plots of the catecholase reactions showed that the kinetics of mushroom tyrosinase (MT), activated by Co"2"+ and Zn"2"+ at different pHs (6, 7, 8 and 9) obeyed the non-essential activation mode. The binding of metal ions to the enzyme increases the maximum velocity of the enzyme due to an increase in the enzyme catalytic constant (k_c_a_t). From the kinetic analysis, dissociation constants of the activator from the enzyme-metal ion complex (K_a) were obtained as 5 x 10"4 M"-"1 and 8.33 x 10"3 M"-"1 for Co"2"+ and Zn"2"+ at pH 9 and 6 respectively. The structural analysis of MT through circular dichroism (CD) and intensive fluorescence spectra revealed that the conformational stability of the enzyme in these pHs reaches its maximum value in the presence of each of the two metal ions