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1

Macromolecular structure of coal  

SciTech Connect

Coals are considered to be three-dimensionally covalently crosslinked macromolecular networks. Solvent swelling techniques, modern polymer theories, and regular solution theory are applied to two bituminous coals in an effort to estimate their crosslink densities. The coals are observed to be extensively, internally hydrogen bonded. The hydrogen bonds serve as crosslinks between the macromolecular chains and contribute substantially to the structural integrity of the coals. Both coals obey the predictions of regular solution theory and their nonpolar solubility parameters (delta) are estimated to be 9.5 (cal/cm/sup 3/)/sup 1/2/. Flory interaction parameters (chi) were calculated for a series of nonpolar solvent-coal pairs. The Flory-Rehner and Kovac equations were then applied to the available data to estimate the crosslink densities of the coals.

Green, T.K.

1984-01-01

2

PHENIX: a comprehensive Python-based system for macromolecular structure solution  

PubMed Central

Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. How­ever, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages and the repeated use of interactive three-dimensional graphics. PHENIX has been developed to provide a comprehensive system for macromolecular crystallo­graphic structure solution with an emphasis on the automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand and, finally, the development of a framework that allows a tight integration between the algorithms. PMID:20124702

Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor; Chen, Vincent B.; Davis, Ian W.; Echols, Nathaniel; Headd, Jeffrey J.; Hung, Li-Wei; Kapral, Gary J.; Grosse-Kunstleve, Ralf W.; McCoy, Airlie J.; Moriarty, Nigel W.; Oeffner, Robert; Read, Randy J.; Richardson, David C.; Richardson, Jane S.; Terwilliger, Thomas C.; Zwart, Peter H.

2010-01-01

3

Phenix - a comprehensive python-based system for macromolecular structure solution  

SciTech Connect

Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages, and the repeated use of interactive three-dimensional graphics. Phenix has been developed to provide a comprehensive system for crystallographic structure solution with an emphasis on automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand, and finally the development of a framework that allows a tight integration between the algorithms.

Terwilliger, Thomas C [Los Alamos National Laboratory; Hung, Li - Wei [Los Alamos National Laboratory; Adams, Paul D [UC BERKELEY; Afonine, Pavel V [UC BERKELEY; Bunkoczi, Gabor [UNIV OF CAMBRIDGE; Chen, Vincent B [DUKE UNIV; Davis, Ian [DUKE UNIV; Echols, Nathaniel [LBNL; Headd, Jeffrey J [DUKE UNIV; Grosse Kunstleve, Ralf W [LBNL; Mccoy, Airlie J [UNIV OF CAMBRIDGE; Moriarty, Nigel W [LBNL; Oeffner, Robert [UNIV OF CAMBRIDGE; Read, Randy J [UNIV OF CAMBRIDGE; Richardson, David C [DUKE UNIV; Richardson, Jane S [DUKE UNIV; Zwarta, Peter H [LBNL

2009-01-01

4

The macromolecular structure of coal  

SciTech Connect

Modern polymer techniques and theories have been very useful in probing both coal structure and coal-solvent interactions in recent years. Although considerable progress has been made in elucidating the macromolecular structure of coals, the work reviewed in this paper represents only a beginning. There remain serious questions about the applicability of the Flory-Rehner equation and its modifications to coals. Clearly, more progress needs to be made if we are to gain a better understanding of coal structure.

Green, T.K.

1987-07-01

5

Criticism to light-heavy water substitution in structural studies of macromolecular aqueous solutions  

NASA Astrophysics Data System (ADS)

We report on measurements performed by Raman scattering and NMR technique on Poly(Ethylene Oxide) solutions both in H 2O and D 2O, at different concentration and temperature values. The Raman analysis of the D-LAM spectral contribution of PEO/H 2O solutions reveals a frequency increase towards values corresponding to the crystal ones and a sharpening of the D-LAM band. Such evidences indicate that the addition of water destroys the intermolecular interactions and stiffens the coil structure, giving rise to a more ordered conformation with respect to that of the melt phase. Concerning the case of PEO/D 2O solutions, notwithstanding the similar behaviour, one observes that the centre frequency and the width of the D-LAM contribution never approach the value obtained in the case of PEO/H 2O, confirming the presence of a remarkable higher degree of disorder. Finally, the temperature analysis of the Raman D-LAM band in PEO/H 2O and PEO/D 2O mixtures, and of the hydrodynamic radius evaluated by NMR in PEO/D 2O solutions reveals that the solvent power of water increases up to T=318 K decreasing at higher temperature in H 2O, whereas in D 2O shows a maximum at T=298 K. The present study shows that Raman scattering and NMR technique represent good tools for characterizing the structural properties of polymers in solution. The experimentally well-ascertained phenomenon reported here provides evidences of different temperature behaviours for PEO in H 2O and D 2O. What conclusively emerges is that isotopic substitution (notably hydrogen/deuterium) widely employed in many fields for manipulating the contrast while perturbing conformational and thermodynamical properties minimally, is, in some cases, open to criticism.

Branca, C.; Magazù, S.; Maisano, G.; Migliardo, P.; Tettamanti, E.

1999-10-01

6

Criticism to light-heavy water substitution in structural studies of macromolecular aqueous solutions  

Microsoft Academic Search

We report on measurements performed by Raman scattering and NMR technique on Poly(Ethylene Oxide) solutions both in H2O and D2O, at different concentration and temperature values. The Raman analysis of the D-LAM spectral contribution of PEO\\/H2O solutions reveals a frequency increase towards values corresponding to the crystal ones and a sharpening of the D-LAM band. Such evidences indicate that the

C. Branca; S. Magazù; G. Maisano; P. Migliardo; E. Tettamanti

1999-01-01

7

The Phenix Software for Automated Determination of Macromolecular Structures  

PubMed Central

X-ray crystallography is a critical tool in the study of biological systems. It is able to provide information that has been a prerequisite to understanding the fundamentals of life. It is also a method that is central to the development of new therapeutics for human disease. Significant time and effort are required to determine and optimize many macromolecular structures because of the need for manual interpretation of complex numerical data, often using many different software packages, and the repeated use of interactive three-dimensional graphics. The Phenix software package has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on automation. This has required the development of new algorithms that minimize or eliminate subjective input in favour of built-in expert-systems knowledge, the automation of procedures that are traditionally performed by hand, and the development of a computational framework that allows a tight integration between the algorithms. The application of automated methods is particularly appropriate in the field of structural proteomics, where high throughput is desired. Features in Phenix for the automation of experimental phasing with subsequent model building, molecular replacement, structure refinement and validation are described and examples given of running Phenix from both the command line and graphical user interface. PMID:21821126

Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor; Chen, Vincent B.; Echols, Nathaniel; Headd, Jeffrey J.; Hung, Li-Wei; Jain, Swati; Kapral, Gary J.; Grosse Kunstleve, Ralf W.; McCoy, Airlie J.; Moriarty, Nigel W.; Oeffner, Robert D.; Read, Randy J.; Richardson, David C.; Richardson, Jane S.; Terwilliger, Thomas C.; Zwart, Peter H.

2011-01-01

8

Size evolution of highly amphiphilic macromolecular solution assemblies via a distinct bimodal pathway  

PubMed Central

The solution self-assembly of macromolecular amphiphiles offers an efficient, bottom-up strategy for producing well--defined nanocarriers, with applications ranging from drug delivery to nanoreactors. Typically, the generation of uniform nanocarrier architecturesis controlled by processing methods that rely upon cosolvent mixtures. These preparation strategies hinge on the assumption that macromolecular solution nanostructures are kinetically stable following transfer from an organic/aqueous cosolvent into aqueous solution. Herein we demonstrate that unequivocal step-change shifts in micelle populations occur over several weeks following transfer into a highly selective solvent. The unexpected micelle growth evolves through a distinct bimodal distribution separated by multiple fusion events and critically depends on solution agitation. Notably, these results underscore fundamental similarities between assembly processes in amphiphilic polymer, small molecule, and protein systems. Moreover, the non-equilibrium micelle size increase can have a major impact on the assumed stability of solution assemblies, for which performance is dictated by nanocarrier size and structure. PMID:24710204

Kelley, Elizabeth G.; Murphy, Ryan P.; Seppala, Jonathan E.; Smart, Thomas P.; Hann, Sarah D.

2014-01-01

9

Macromolecular structure of low rank coals and lignites  

SciTech Connect

The low rank coals, lignites and subbituminous coals, are considered to be three dimensionally covalently crosslinked macromolecules. The solvent swelling methodology used to characterize the macromolecular structure of bituminous coals is extended to the lower-rank coals. The pyridine-extracted subbituminous coal obeyed the predictions of regular solution theory, while the pyridine-extracted lignites did not. The non-polar solubility parameter of the pyridine-extracted subbituminous coal was estimated to be 9.5 (cal/cm/sup 3/)/sup 1/2/. The O-acetylated and O-methylated subbituminous coals were assigned solubility parameters of 9.2 (cal/cm/sup 3/)/sup 1/2/. Solubility parameters of 9.2 and 9.1 (cal/cm/sup 3/)/sup 1/2/ were assigned to the two O-acetylated lignite samples. Flory Interaction Parameters were calculated for a series of non-polar solvent-coal pairs. The Flory-Rehner and Kovac Equations were applied to the solvent swelling data to estimate crosslink densities and the number average molecular weight between crosslinks of the O-acetylated lignites and pyridine-extracted subbituminous coal. The low rank coals contain hydrogen bonds which serve as crosslinks in the coal network. Solvent swelling experiments with non-polar solvents indicated the removal of ionic bonds was found to have little effect on the macromolecular structure of the lower rank coals.

Shawver, S.E.

1986-01-01

10

Coal structure and reactivity: the macromolecular structure of coal. Final report  

SciTech Connect

Coals are considered to be three-dimensionally covalently crosslinked macromolecular networks. Solvent swelling techniques, modern polymer theories, and regular solution theory are applied to two bituminous coals in an effort to estimate their crosslink densities. The coals are observed to be extensively, internally hydrogen bonded. The hydrogen bonds serve as crosslinks between the macromolecular chains and contribute substantially to the structural integrity of the coals. Both coals obey the predictions of regular solution theory and their nonpolar solubility parameters are estimated to be 9.5 (cal/cm/sup 3/)/sup 1/2/. Flory interaction parameters were calculated for a series of nonpolar solvent-coal pairs. The Flory-Rehner and Kovac equations were then applied to the available data to estimate the crosslink densities of the coals. 124 refs., 37 figs., 27 tabs.

Larsen, J.W.; Green, T.K.

1984-03-01

11

Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination  

Microsoft Academic Search

A new software suite, called Crystallography & NMR System (CNS), has been developed for macromolecular structure determination by X-ray crystallography or solution nuclear magnetic resonance (NMR) spectro- scopy. In contrast to existing structure-determination programs the architecture of CNS is highly flexible, allowing for extension to other structure-determination methods, such as electron microscopy and solid-state NMR spectroscopy. CNS has a hierarchical

AXEL T. BRUNGER; PAUL D. ADAMS; G. MARIUS CLORE; WARREN L. DELANO; PIET GROS; RALF W. GROSSE; JIAN-SHENG JIANG; MICHAEL NILGES; NAVRAJ S. PANNU; RANDY J. READ; LUKE M. RICE; THOMAS SIMONSON; GREGORY L. WARREN; John Kuszewski

1998-01-01

12

Fast native-SAD phasing for routine macromolecular structure determination.  

PubMed

We describe a data collection method that uses a single crystal to solve X-ray structures by native SAD (single-wavelength anomalous diffraction). We solved the structures of 11 real-life examples, including a human membrane protein, a protein-DNA complex and a 266-kDa multiprotein-ligand complex, using this method. The data collection strategy is suitable for routine structure determination and can be implemented at most macromolecular crystallography synchrotron beamlines. PMID:25506719

Weinert, Tobias; Olieric, Vincent; Waltersperger, Sandro; Panepucci, Ezequiel; Chen, Lirong; Zhang, Hua; Zhou, Dayong; Rose, John; Ebihara, Akio; Kuramitsu, Seiki; Li, Dianfan; Howe, Nicole; Schnapp, Gisela; Pautsch, Alexander; Bargsten, Katja; Prota, Andrea E; Surana, Parag; Kottur, Jithesh; Nair, Deepak T; Basilico, Federica; Cecatiello, Valentina; Pasqualato, Sebastiano; Boland, Andreas; Weichenrieder, Oliver; Wang, Bi-Cheng; Steinmetz, Michel O; Caffrey, Martin; Wang, Meitian

2015-02-01

13

Cryo-Electron Tomography for Structural Characterization of Macromolecular Complexes  

PubMed Central

Cryo-electron tomography (cryo-ET) is an emerging 3-D reconstruction technology that combines the principles of tomographic 3-D reconstruction with the unmatched structural preservation of biological material embedded in vitreous ice. Cryo-ET is particularly suited to investigating cell-biological samples and large macromolecular structures that are too polymorphic to be reconstructed by classical averaging-based 3-D reconstruction procedures. This unit aims to make cryo-ET accessible to newcomers and discusses the specialized equipment required, as well as the relevant advantages and hurdles associated with sample preparation by vitrification and cryo-ET. Protocols describe specimen preparation, data recording and 3-D data reconstruction for cryo-ET, with a special focus on macromolecular complexes. A step-by-step procedure for specimen vitrification by plunge freezing is provided, followed by the general practicalities of tilt-series acquisition for cryo-ET, including advice on how to select an area appropriate for acquiring a tilt series. A brief introduction to the underlying computational reconstruction principles applied in tomography is described, along with instructions for reconstructing a tomogram from cryo-tilt series data. Finally, a method is detailed for extracting small subvolumes containing identical macromolecular structures from tomograms for alignment and averaging as a means to increase the signal-to-noise ratio and eliminate missing wedge effects inherent in tomographic reconstructions. PMID:21842467

Cope, Julia; Heumann, John; Hoenger, Andreas

2011-01-01

14

Modeling Symmetric Macromolecular Structures in Rosetta3  

PubMed Central

Symmetric protein assemblies play important roles in many biochemical processes. However, the large size of such systems is challenging for traditional structure modeling methods. This paper describes the implementation of a general framework for modeling arbitrary symmetric systems in Rosetta3. We describe the various types of symmetries relevant to the study of protein structure that may be modeled using Rosetta's symmetric framework. We then describe how this symmetric framework is efficiently implemented within Rosetta, which restricts the conformational search space by sampling only symmetric degrees of freedom, and explicitly simulates only a subset of the interacting monomers. Finally, we describe structure prediction and design applications that utilize the Rosetta3 symmetric modeling capabilities, and provide a guide to running simulations on symmetric systems. PMID:21731614

DiMaio, Frank; Leaver-Fay, Andrew; Bradley, Phil; Baker, David; André, Ingemar

2011-01-01

15

Macromolecular structure analysis and effective liquefaction pretreatment. Final report  

SciTech Connect

This project was concerned with characterizing the changes in coal macromolecular structure, that are of significance for liquefaction pretreatments of coal. The macromolecular structure of the insoluble portion of coal is difficult to characterize. Techniques that do so indirectly (based upon, for example, NMR and FTIR characterizations of atomic linkages) are not particularly sensitive for this purpose. Techniques that characterize the elastic structure (such as solvent swelling) are much more sensitive to subtle changes in the network structure. It is for this reason that we focused upon these techniques. The overall objective involved identifying pretreatments that reduce the crosslinking (physical or chemical) of the network structure, and thus lead to materials that can be handled to a greater extent by traditional liquid-phase processing techniques. These techniques tend to be inherently more efficient at producing desirable products. This report is divided into seven chapters. Chapter II summarizes the main experimental approaches used throughout the project, and summarizes the main findings on the Argonne Premium coal samples. Chapter III considers synergistic effects of solvent pairs. It is divided into two subsections. The first is concerned with mixtures of CS{sub 2} with electron donor solvents. The second subsection is concerned with aromatic hydrocarbon - alcohol or hydrocarbon - alcohol mixtures, as might be of interest for preliquefaction delivery of catalysts into bituminous coals. Chapter IV deals with questions of how oxidation might influence the results that are obtained. Chapter V briefly details what conclusions may be drawn concerning the elastic behavior of coals, and the effects of thermal treatments on this behavior. Chapter VI is concerned with theories to describe the action of solvents that are capable of dissociating non-covalent crosslinks. Finally, Chapter VII discusses the practical implications of the study.

Suuberg, E.M.; Yun, Y.; Lilly, W.D.; Leung, K.; Gates, T.; Otake, Y.; Deevi, S.C.

1994-07-01

16

Conformational States of Macromolecular Assemblies Explored by Integrative Structure Calculation  

PubMed Central

Summary A detailed description of macromolecular assemblies in multiple conformational states can be very valuable for understanding cellular processes. At present, structural determination of most assemblies in different biologically relevant conformations cannot be achieved by a single technique and thus requires an integrative approach that combines information from multiple sources. Different techniques require different computational methods to allow efficient and accurate data processing and analysis. Here, we summarize the latest advances and future challenges in computational methods that help the interpretation of data from two techniques—mass spectrometry and three-dimensional cryo-electron microscopy (with focus on alignment and classification of heterogeneous subtomograms from cryo-electron tomography). We evaluate how new developments in these two broad fields will lead to further integration with atomic structures to broaden our picture of the dynamic behavior of assemblies in their native environment. PMID:24010709

Thalassinos, Konstantinos; Pandurangan, Arun Prasad; Xu, Min; Alber, Frank; Topf, Maya

2013-01-01

17

Macromolecular coal structure as revealed by novel diffusion tests  

SciTech Connect

The main goal of the present work was the elucidation of the mechanistic characteristics of dynamic transport of various penetrants (solvents) in thin sections of coals by examining their penetrant uptake, front swelling and stress development. An important objective of this work was the study of coal network structure in different thermodynamically compatible penetrants and the analysis of dynamic swelling in terms of present anomalous transport theories. Interferometry/polariscopy, surface image analysis and related techniques were used to quantify the stresses and solvent concentration profiles in these sections. Dynamic and equilibrium swelling behavior were correlated using the polar interaction contributions of the solvent solubility parameters. The penetrant front position was followed in thin coal sections as a function of time. The initial front velocity was calculated for various coals and penetrants. Our penetrant studies with thin coal section from the same coal sample but with different thickness show that within the range of 150 {mu}m to 1500{mu}m the transport mechanism of dimethyl formamide in the macromolecular coal network is non-Fickian. In fact, for the thickest samples the transport mechanism is predominately Case-II whereas in the thinner samples penetrant uptake may be diffusion-controlled. Studies in various penetrants such as acetone, cyclohexane, methanol, methyl ethyl ketone, toluene and methylene chloride indicated that penetrant transport is a non-Fickian phenomenon. Stresses and cracks were observed for transport of methylene chloride. 73 refs., 88 figs., 15 tabs.

Peppas, N.A.; Olivares, J.; Drummond, R.; Lustig, S.

1990-01-01

18

Macromolecular ab initio phasing enforcing secondary and tertiary structure  

PubMed Central

Ab initio phasing of macromolecular structures, from the native intensities alone with no experimental phase information or previous particular structural knowledge, has been the object of a long quest, limited by two main barriers: structure size and resolution of the data. Current approaches to extend the scope of ab initio phasing include use of the Patterson function, density modification and data extrapolation. The authors’ approach relies on the combination of locating model fragments such as polyalanine ?-helices with the program PHASER and density modification with the program SHELXE. Given the difficulties in discriminating correct small substructures, many putative groups of fragments have to be tested in parallel; thus calculations are performed in a grid or supercomputer. The method has been named after the Italian painter Arcimboldo, who used to compose portraits out of fruit and vegetables. With ARCIMBOLDO, most collections of fragments remain a ‘still-life’, but some are correct enough for density modification and main-chain tracing to reveal the protein’s true portrait. Beyond ?-helices, other fragments can be exploited in an analogous way: libraries of helices with modelled side chains, ?-strands, predictable fragments such as DNA-binding folds or fragments selected from distant homologues up to libraries of small local folds that are used to enforce nonspecific tertiary structure; thus restoring the ab initio nature of the method. Using these methods, a number of unknown macromolecules with a few thousand atoms and resolutions around 2?Å have been solved. In the 2014 release, use of the program has been simplified. The software mediates the use of massive computing to automate the grid access required in difficult cases but may also run on a single multicore workstation (http://chango.ibmb.csic.es/ARCIMBOLDO_LITE) to solve straightforward cases. PMID:25610631

Millán, Claudia; Sammito, Massimo; Usón, Isabel

2015-01-01

19

Facilitating structure determination: workshop on robotics andautomation in macromolecular crystallography  

SciTech Connect

As part of the annual Advanced Light Source (ALS) andStanford Synchrotron Radiation Laboratory (SSRL) Users' Meeting inOctober of this year, the macromolecular crystallography staff at bothsynchrotrons held a joint hands-on workshop to address automation issuesin crystal mounting and data collection at the beamline. This paperdescribes the ALS portion of the workshop, while the accompanying paperreviews the SSRL workshop.

Ralston, Corie; Cork, C.W.; McDermott, G.; Earnest, T.N.

2006-03-28

20

Microelectrophoretic study of calcium oxalate monohydrate in macromolecular solutions  

NASA Technical Reports Server (NTRS)

Electrophoretic mobilities were measured for calcium oxalate monohydrate (COM) in solutions containing macromolecules. Two mucopolysaccharides (sodium heparin and chondroitin sulfate) and two proteins (positively charged lysozyme and negatively charged bovine serum albumin) were studied as adsorbates. The effects of pH, calcium oxalate surface charge (varied by calcium or oxalate ion activity), and citrate concentration were investigated. All four macromolecules showed evidence for adsorption. The macromolecule concentrations needed for reversing the surface charge indicated that the mucopolysaccharides have greater affinity for the COM surface than the proteins. Citrate ions at high concentrations appear to compete effectively with the negative protein for surface sites but show no evidence for competing with the positively charged protein.

Curreri, P. A.; Onoda, G. Y., Jr.; Finlayson, B.

1987-01-01

21

The electrokinetic behavior of calcium oxalate monohydrate in macromolecular solutions  

NASA Technical Reports Server (NTRS)

Electrophoretic mobilities were measured for calcium oxalate monohydrate (COM) in solutions containing macromolecules. Two mucopolysaccharides (sodium heparin and chrondroitin sulfate) and two proteins (positively charged lysozyme and negatively charged bovine serum albumin) were studied as adsorbates. The effects of pH, calcium oxalate surface charge (varied by calcium or oxalate ion activity), and citrate concentration were investigated. All four macromolecules showed evidence for chemical adsorption. The macromolecule concentrations needed for reversing the surface charge indicated that the mucopopolysacchrides have greater affinity for the COM surface than the proteins. The amount of proteins that can chemically adsorb appears to be limited to approximately one monomolecular layer. When the surface charge is high, an insufficient number of proteins can chemically adsorb to neutralize or reverse the surface charge. The remaining surface charge is balanced by proteins held near the surface by longer range electrostatic forces only. Citrate ions at high concentrations appear to compete effectively with the negative protein for surface sites but show no evidence for competing with the positively charged protein.

Curreri, P. A.; Onoda, G. Y., Jr.; Finlayson, B.

1988-01-01

22

MOLMOL: A program for display and analysis of macromolecular structures  

Microsoft Academic Search

MOLMOL is a molecular graphics program for display, analysis, and manipulation of three-dimensional structures of biological macromolecules, with special emphasis on nuclear magnetic resonance (NMR) solution structures of proteins and nucleic acids. MOLMOL has a graphical user interface with menus, dialog boxes, and on-line help. The display possibilities include conventional presentation, as well as novel schematic drawings, with the option

Reto Koradi; Martin Billeter; Kurt Wüthrich

1996-01-01

23

Recent developments in phasing and structure refinement for macromolecular crystallography  

PubMed Central

Summary Central to crystallographic structure solution is obtaining accurate phases in order to build a molecular model, ultimately followed by refinement of that model to optimize its fit to the experimental diffraction data and prior chemical knowledge. Recent advances in phasing and model refinement and validation algorithms make it possible to arrive at better electron density maps and more accurate models. PMID:19700309

Adams, Paul D.; Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Read, Randy J.; Richardson, Jane S.; Richardson, David C.; Terwilliger, Thomas C.

2009-01-01

24

The Neurobiologist's Guide to Structural Biology: A Primer on Why Macromolecular Structure Matters and How to Evaluate Structural Data  

PubMed Central

Structural biology now plays a prominent role in addressing questions central to understanding how excitable cells function. Although interest in the insights gained from the definition and dissection of macromolecular anatomy is high, many neurobiologists remain unfamiliar with the methods employed. This primer aims to help neurobiologists understand approaches for probing macromolecular structure and where the limits and challenges remain. Using examples of macromolecules with neurobiological importance, the review covers X-ray crystallography, electron microscopy (EM), small-angle X-ray scattering (SAXS), and nuclear magnetic resonance (NMR) and biophysical methods with which these approaches are often paired: isothermal titration calorimetry (ITC), equilibrium analytical ultracentifugation, and molecular dynamics (MD). PMID:17521566

Minor, Daniel L.

2010-01-01

25

between the nucleus and cytoplasm occurs through large macromolecular structures, the nuclear pores. Quantitative  

E-print Network

requirement for nuclear import and export. In reality, a family of importin -related receptors is used363 between the nucleus and cytoplasm occurs through large macromolecular structures, the nuclear pores. Quantitative scanning transmission electron microscopy has estimated the mass of a nuclear pore

Forbes, Douglass

26

Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination.  

PubMed

The number of macromolecular structures deposited in the Protein Data Bank now approaches 100,000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation. PMID:24034303

Wlodawer, Alexander; Minor, Wladek; Dauter, Zbigniew; Jaskolski, Mariusz

2013-11-01

27

Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination  

PubMed Central

The number of macromolecular structures deposited in the Protein Data Bank now approaches 100 000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation. PMID:24034303

Wlodawer, Alexander; Minor, Wladek; Dauter, Zbigniew; Jaskolski, Mariusz

2014-01-01

28

The R-factor gap in macromolecular crystallography: an untapped potential for insights on accurate structures  

PubMed Central

In macromolecular crystallography, the agreement between observed and predicted structure factors (Rcryst and Rfree) is seldom better than 20%. This is much larger than the estimate of experimental error (Rmerge). The difference between Rcryst and Rmerge is the R-factor gap. There is no such gap in small-molecule crystallography, for which calculated structure factors are generally considered more accurate than the experimental measurements. Perhaps the true noise level of macromolecular data is higher than expected? Or is the gap caused by inaccurate phases that trap refined models in local minima? By generating simulated diffraction patterns using the program MLFSOM, and including every conceivable source of experimental error, we show that neither is the case. Processing our simulated data yielded values that were indistinguishable from those of real data for all crystallographic statistics except the final Rcryst and Rfree. These values decreased to 3.8% and 5.5% for simulated data, suggesting that the reason for high R-factors in macromolecular crystallography is neither experimental error nor phase bias, but rather an underlying inadequacy in the models used to explain our observations. The present inability to accurately represent the entire macromolecule with both its flexibility and its protein-solvent interface may be improved by synergies between small-angle X-ray scattering, computational chemistry and crystallography. The exciting implication of our finding is that macromolecular data contain substantial hidden and untapped potential to resolve ambiguities in the true nature of the nanoscale, a task that the second century of crystallography promises to fulfill. Database Coordinates and structure factors for the real data have been submitted to the Protein Data Bank under accession 4tws. PMID:25040949

Holton, James M; Classen, Scott; Frankel, Kenneth A; Tainer, John A

2014-01-01

29

Denatured State Structural Property Determines Protein Stabilization by Macromolecular Crowding: A Thermodynamic and Structural Approach  

PubMed Central

Understanding of protein structure and stability gained to date has been acquired through investigations made under dilute conditions where total macromolecular concentration never surpasses 10 g l?1. However, biological macromolecules are known to evolve and function under crowded intracellular environments that comprises of proteins, nucleic acids, ribosomes and carbohydrates etc. Crowded environment is known to result in altered biological properties including thermodynamic, structural and functional aspect of macromolecules as compared to the macromolecules present in our commonly used experimental dilute buffers (for example, Tris HCl or phosphate buffer). In this study, we have investigated the thermodynamic and structural consequences of synthetic crowding agent (Ficoll 70) on three different proteins (Ribonuclease-A, lysozyme and holo ?-lactalbumin) at different pH values. We report here that the effect of crowding is protein dependent in terms of protein thermal stability and structure. We also observed that the structural characteristics of the denatured state determines if crowding will have an effect or not on the protein stability. PMID:24265729

Mittal, Shruti; Singh, Laishram Rajendrakumar

2013-01-01

30

Evolutionary Genomics: Linking Macromolecular Structure, Genomes and Biological Networks  

Microsoft Academic Search

The recent genomic revolution has resulted in massive acquisition of nucleic acid sequences. Hundreds of genomes have been\\u000a completely sequenced yielding tens of billions of base pairs, millions of protein sequences, and thousands of functional RNA\\u000a molecules important for cell development and homeostasis. This effort outpaces structural genomics with its tens of thousands\\u000a of three-dimensional models of molecular structure embedded

Gustavo Caetano-Anollés

31

[18] improving structures using all-atom contacts 385 The methodology of macromolecular crystallography is mature, powerful,  

E-print Network

[18] improving structures using all-atom contacts 385 The methodology of macromolecular of protein and nucleic acid crystal structures. [18] New Tools and Data for Improving Structures, Using All-atom criteria for protein structure validation: (1) development of the all-atom contact method, which can

Richardson, David

32

Structure, assembly and dynamics of macromolecular complexes by single particle cryo-electron microscopy  

PubMed Central

Background Proteins in their majority act rarely as single entities. Multisubunit macromolecular complexes are the actors in most of the cellular processes. These nanomachines are hold together by weak protein-protein interactions and undergo functionally important conformational changes. TFIID is such a multiprotein complex acting in eukaryotic transcription initiation. This complex is first to be recruited to the promoter of the genes and triggers the formation of the transcription preinitiation complex involving RNA polymerase II which leads to gene transcription. The exact role of TFIID in this process is not yet understood. Methods Last generation electron microscopes, improved data collection and new image analysis tools made it possible to obtain structural information of biological molecules at atomic resolution. Cryo-electron microscopy of vitrified samples visualizes proteins in a fully hydrated, close to native state. Molecular images are recorded at liquid nitrogen temperature in low electron dose conditions to reduce radiation damage. Digital image analysis of these noisy images aims at improving the signal-to-noise ratio, at separating distinct molecular views and at reconstructing a three-dimensional model of the biological particle. Results Using these methods we showed the early events of an activated transcription initiation process. We explored the interaction of the TFIID coactivator with the yeast Rap1 activator, the transcription factor TFIIA and the promoter DNA. We demonstrated that TFIID serves as an assembly platform for transient protein-protein interactions, which are essential for transcription initiation. Conclusions Recent developments in electron microscopy have provided new insights into the structural organization and the dynamic reorganization of large macromolecular complexes. Examples of near-atomic resolutions exist but the molecular flexibility of macromolecular complexes remains the limiting factor in most case. Electron microscopy has the potential to provide both structural and dynamic information of biological assemblies in order to understand the molecular mechanisms of their functions. PMID:24565374

2013-01-01

33

Recovering a Representative Conformational Ensemble from Underdetermined Macromolecular Structural Data  

PubMed Central

Structural analysis of proteins and nucleic acids is complicated by their inherent flexibility, conferred, for example, by linkers between their contiguous domains. Therefore, the macromolecule needs to be represented by an ensemble of conformations instead of a single conformation. Determining this ensemble is challenging because the experimental data are a convoluted average of contributions from multiple conformations. As the number of the ensemble degrees of freedom generally greatly exceeds the number of independent observables, directly deconvolving experimental data into a representative ensemble is an ill-posed problem. Recent developments in sparse approximations and compressive sensing have demonstrated that useful information can be recovered from underdetermined (ill-posed) systems of linear equations by using sparsity regularization. Inspired by these advances, we designed Sparse Ensemble Selection (SES) method for recovering multiple conformations from a limited number of observations. SES is more general and accurate than previously published minimum-ensemble methods, and we use it to obtain representative conformational ensembles of Lys48-linked di-ubiquitin, characterized by the residual dipolar coupling data measured at several pH conditions. These representative ensembles are validated against NMR chemical shift perturbation data and compared to maximum-entropy results. The SES method reproduced and quantified the previously observed pH dependence of the major conformation of Lys48-linked di-ubiquitin, and revealed lesser-populated conformations that are pre-organized for binding known di-ubiquitin receptors, thus providing insights into possible mechanisms of receptor recognition by polyubiquitin. SES is applicable to any experimental observables that can be expressed as a weighted linear combination of data for individual states. PMID:24093873

Berlin, Konstantin; Castañeda, Carlos A.; Schneidman-Duhovny, Dina; Sali, Andrej; Nava-Tudela, Alfredo; Fushman, David

2013-01-01

34

Accurate macromolecular structures using minimal measurements from X-ray free-electron lasers  

PubMed Central

X-ray free-electron laser (XFEL) sources enable the use of crystallography to solve three-dimensional macromolecular structures under native conditions and free from radiation damage. Results to date, however, have been limited by the challenge of deriving accurate Bragg intensities from a heterogeneous population of microcrystals, while at the same time modeling the X-ray spectrum and detector geometry. Here we present a computational approach designed to extract statistically significant high-resolution signals from fewer diffraction measurements. PMID:24633409

Hattne, Johan; Echols, Nathaniel; Tran, Rosalie; Kern, Jan; Gildea, Richard J.; Brewster, Aaron S.; Alonso-Mori, Roberto; Glöckner, Carina; Hellmich, Julia; Laksmono, Hartawan; Sierra, Raymond G.; Lassalle-Kaiser, Benedikt; Lampe, Alyssa; Han, Guangye; Gul, Sheraz; DiFiore, Dörte; Milathianaki, Despina; Fry, Alan R.; Miahnahri, Alan; White, William E.; Schafer, Donald W.; Seibert, M. Marvin; Koglin, Jason E.; Sokaras, Dimosthenis; Weng, Tsu-Chien; Sellberg, Jonas; Latimer, Matthew J.; Glatzel, Pieter; Zwart, Petrus H.; Grosse-Kunstleve, Ralf W.; Bogan, Michael J.; Messerschmidt, Marc; Williams, Garth J.; Boutet, Sébastien; Messinger, Johannes; Zouni, Athina; Yano, Junko; Bergmann, Uwe; Yachandra, Vittal K.; Adams, Paul D.; Sauter, Nicholas K.

2014-01-01

35

Capillary Viscometer for Fully Automated Measurement of the Concentration and Shear Dependence of the Viscosity of Macromolecular Solutions  

PubMed Central

The construction and operation of a novel viscometer/rheometer are described. The instrument is designed to measure the viscosity of a macromolecular solution while automatically varying both solute concentration and shear rate. Viscosity is calculated directly from Poiseuille's Law, given the measured difference in pressure between two ends of a capillary tube through which the solution is flowing at a known rate. The instrument requires as little as 0.75 ml of a solution to provide a full profile of viscosity as a function of concentration and shear rate, and can measure viscosities as high as 500 cP and as low as 1 cP, at shear rates between 10 and 2 × 103 s-1. The results of control experiments are presented to document the accuracy and precision of measurement at both low and high concentration of synthetic polymers and proteins. PMID:23130673

Grupi, Asaf; Minton, Allen P.

2014-01-01

36

PURY: a database of geometric restraints of hetero compounds for refinement in complexes with macromolecular structures.  

PubMed

The number and variety of macromolecular structures in complex with ;hetero' ligands is growing. The need for rapid delivery of correct geometric parameters for their refinement, which is often crucial for understanding the biological relevance of the structure, is growing correspondingly. The current standard for describing protein structures is the Engh-Huber parameter set. It is an expert data set resulting from selection and analysis of the crystal structures gathered in the Cambridge Structural Database (CSD). Clearly, such a manual approach cannot be applied to the vast and ever-growing number of chemical compounds. Therefore, a database, named PURY, of geometric parameters of chemical compounds has been developed, together with a server that accesses it. PURY is a compilation of the whole CSD. It contains lists of atom classes and bonds connecting them, as well as angle, chirality, planarity and conformation parameters. The current compilation is based on CSD 5.28 and contains 1978 atom classes and 32,702 bonding, 237,068 angle, 201,860 dihedral and 64,193 improper geometric restraints. Analysis has confirmed that the restraints from the PURY database are suitable for use in macromolecular crystal structure refinement and should be of value to the crystallographic community. The database can be accessed through the web server http://pury.ijs.si/, which creates topology and parameter files from deposited coordinates in suitable forms for the refinement programs MAIN, CNS and REFMAC. In the near future, the server will move to the CSD website http://pury.ccdc.cam.ac.uk/. PMID:19020347

Andrejasic, Miha; Praaenikar, Jure; Turk, Dusan

2008-11-01

37

Automated structure solution with the PHENIX suite  

SciTech Connect

Significant time and effort are often required to solve and complete a macromolecular crystal structure. The development of automated computational methods for the analysis, solution, and completion of crystallographic structures has the potential to produce minimally biased models in a short time without the need for manual intervention. The PHENIX software suite is a highly automated system for macromolecular structure determination that can rapidly arrive at an initial partial model of a structure without significant human intervention, given moderate resolution, and good quality data. This achievement has been made possible by the development of new algorithms for structure determination, maximum-likelihood molecular replacement (PHASER), heavy-atom search (HySS), template- and pattern-based automated model-building (RESOLVE, TEXTAL), automated macromolecular refinement (phenix. refine), and iterative model-building, density modification and refinement that can operate at moderate resolution (RESOLVE, AutoBuild). These algorithms are based on a highly integrated and comprehensive set of crystallographic libraries that have been built and made available to the community. The algorithms are tightly linked and made easily accessible to users through the PHENIX Wizards and the PHENIX GUI.

Terwilliger, Thomas C [Los Alamos National Laboratory; Zwart, Peter H [LBNL; Afonine, Pavel V [LBNL; Grosse - Kunstleve, Ralf W [LBNL

2008-01-01

38

Automated Structure Solution with the PHENIX Suite  

SciTech Connect

Significant time and effort are often required to solve and complete a macromolecular crystal structure. The development of automated computational methods for the analysis, solution and completion of crystallographic structures has the potential to produce minimally biased models in a short time without the need for manual intervention. The PHENIX software suite is a highly automated system for macromolecular structure determination that can rapidly arrive at an initial partial model of a structure without significant human intervention, given moderate resolution and good quality data. This achievement has been made possible by the development of new algorithms for structure determination, maximum-likelihood molecular replacement (PHASER), heavy-atom search (HySS), template and pattern-based automated model-building (RESOLVE, TEXTAL), automated macromolecular refinement (phenix.refine), and iterative model-building, density modification and refinement that can operate at moderate resolution (RESOLVE, AutoBuild). These algorithms are based on a highly integrated and comprehensive set of crystallographic libraries that have been built and made available to the community. The algorithms are tightly linked and made easily accessible to users through the PHENIX Wizards and the PHENIX GUI.

Zwart, Peter H.; Zwart, Peter H.; Afonine, Pavel; Grosse-Kunstleve, Ralf W.; Hung, Li-Wei; Ioerger, Tom R.; McCoy, A.J.; McKee, Eric; Moriarty, Nigel; Read, Randy J.; Sacchettini, James C.; Sauter, Nicholas K.; Storoni, L.C.; Terwilliger, Tomas C.; Adams, Paul D.

2008-06-09

39

Automated MAD and MIR structure solution  

PubMed Central

Obtaining an electron-density map from X-ray diffraction data can be difficult and time-consuming even after the data have been collected, largely because MIR and MAD structure determinations currently require many subjective evaluations of the qualities of trial heavy-atom partial structures before a correct heavy-atom solution is obtained. A set of criteria for evaluating the quality of heavy-atom partial solutions in macromolecular crystallography have been developed. These have allowed the conversion of the crystal structure-solution process into an optimization problem and have allowed its automation. The SOLVE software has been used to solve MAD data sets with as many as 52 selenium sites in the asymmetric unit. The automated structure-solution process developed is a major step towards the fully automated structure-determination, model-building and refinement procedure which is needed for genomic scale structure determinations. PMID:10089316

Terwilliger, Thomas C.; Berendzen, Joel

1999-01-01

40

A 3D image filter for parameter-free segmentation of macromolecular structures from electron tomograms.  

PubMed

3D image reconstruction of large cellular volumes by electron tomography (ET) at high (? 5 nm) resolution can now routinely resolve organellar and compartmental membrane structures, protein coats, cytoskeletal filaments, and macromolecules. However, current image analysis methods for identifying in situ macromolecular structures within the crowded 3D ultrastructural landscape of a cell remain labor-intensive, time-consuming, and prone to user-bias and/or error. This paper demonstrates the development and application of a parameter-free, 3D implementation of the bilateral edge-detection (BLE) algorithm for the rapid and accurate segmentation of cellular tomograms. The performance of the 3D BLE filter has been tested on a range of synthetic and real biological data sets and validated against current leading filters-the pseudo 3D recursive and Canny filters. The performance of the 3D BLE filter was found to be comparable to or better than that of both the 3D recursive and Canny filters while offering the significant advantage that it requires no parameter input or optimisation. Edge widths as little as 2 pixels are reproducibly detected with signal intensity and grey scale values as low as 0.72% above the mean of the background noise. The 3D BLE thus provides an efficient method for the automated segmentation of complex cellular structures across multiple scales for further downstream processing, such as cellular annotation and sub-tomogram averaging, and provides a valuable tool for the accurate and high-throughput identification and annotation of 3D structural complexity at the subcellular level, as well as for mapping the spatial and temporal rearrangement of macromolecular assemblies in situ within cellular tomograms. PMID:22479430

Ali, Rubbiya A; Landsberg, Michael J; Knauth, Emily; Morgan, Garry P; Marsh, Brad J; Hankamer, Ben

2012-01-01

41

Code Generation Through Annotation of Macromolecular Structure Data John Biggs 1 , Calton Pu 1 , and Philip Bourne 2  

E-print Network

Code Generation Through Annotation of Macromolecular Structure Data John Biggs 1 , Calton Pu 1 and code generator are provided. Introduction Data in many areas of molecular biology are growing uses a rapidly evolving data annotation scheme is time consuming and expensive. At the same time

Bourne, Philip E.

42

Effect of microwave radiation on the macromolecular, morphological and crystallographic structures of sisal fiber  

NASA Astrophysics Data System (ADS)

Experiments have been performed to find out the effectiveness of the microwave radiation on the modification of the sisal fiber. The idea of taking the high frequency microwave for modification of the sisal is fueled by the present environmental and energy crisis. Physical properties of the fiber have been modified significantly after microwave irradiation under different conditions in terms of power and time. Macromolecular parameters of the fiber are characterized by the Small angle X-ray Scattering characterization (SAXS) technique. These parameters have been found to be changed significantly after the microwave heat treatment as compare to the raw fiber. The fibers that are irradiated for 4 min under 320 W microwave power (320W4) are found to have least distortion, defect, enhanced density, surface roughness, improved crystallinity, and hydrophobicity. However, the degradation of the structural component and crystallinity of the fiber are observed at higher power and higher treatment period. The chemical structure of the microwave treated fiber does not change much except at higher power and prolong treatment period.

Patra, Annapurna; Bisoyi, Dillip K.; Manda, Prem K.; Singh, A. K.

2013-09-01

43

Free kick instead of cross-validation in maximum-likelihood refinement of macromolecular crystal structures  

PubMed Central

The refinement of a molecular model is a computational procedure by which the atomic model is fitted to the diffraction data. The commonly used target in the refinement of macromolecular structures is the maximum-likelihood (ML) function, which relies on the assessment of model errors. The current ML functions rely on cross-validation. They utilize phase-error estimates that are calculated from a small fraction of diffraction data, called the test set, that are not used to fit the model. An approach has been developed that uses the work set to calculate the phase-error estimates in the ML refinement from simulating the model errors via the random displacement of atomic coordinates. It is called ML free-kick refinement as it uses the ML formulation of the target function and is based on the idea of freeing the model from the model bias imposed by the chemical energy restraints used in refinement. This approach for the calculation of error estimates is superior to the cross-validation approach: it reduces the phase error and increases the accuracy of molecular models, is more robust, provides clearer maps and may use a smaller portion of data for the test set for the calculation of R free or may leave it out completely. PMID:25478831

Pražnikar, Jure; Turk, Dušan

2014-01-01

44

The Online Macromolecular Museum  

NSDL National Science Digital Library

The Online Macromolecular Museum (OMM) is a site for the display and study of macromolecules. Macromolecular structures, as discovered by crystallographic or NMR methods, are scientific objects in much the same sense as fossil bones or dried specimens: they can be archived, studied, and displayed in aesthetically pleasing, educational exhibits. Hence, a museum seems an appropriate designation for the collection of displays that we are assembling. The OMM's exhibits are interactive Jmol tutorials on individual molecules in which hypertextual explanations of important biochemical features are linked to illustrative renderings of the molecule at hand.

David Marcey (CLU;Biology)

2011-08-01

45

Online Macromolecular Museum  

NSDL National Science Digital Library

The Online Macromolecular Museum (OMM) is a site for the display and study of macromolecules. Macromolecular structures, as discovered by crystallographic or NMR methods, are scientific objects in much the same sense as fossil bones or dried specimens: they can be archived, studied, and displayed in aesthetically pleasing, educational exhibits. Hence, a museum seems an appropriate designation for the collection of displays that we are assembling. The OMM's exhibits are interactive tutorials on individual molecules in which hypertextual explanations of important biochemical features are linked to illustrative renderings of the molecule at hand.

David Marcey (CLU;Biology)

2012-06-01

46

Hydropyrolysis of insoluble carbonaceous matter in the Murchison meteorite: new insights into its macromolecular structure  

NASA Astrophysics Data System (ADS)

The major organic component of carbonaceous chondrites is a solvent-insoluble, high molecular weight macromolecular material that constitutes at least 70% of the total organic content in these meteorites. Analytical pyrolysis is often used to thermally decompose macromolecular organic matter in an inert atmosphere into lower molecular weight fragments that are more amenable to conventional organic analytical techniques. Hydropyrolysis refers to pyrolysis assisted by high hydrogen gas pressures and a dispersed catalytically-active molybdenum sulfide phase. Hydropyrolysis of meteorites has not been attempted previously although it is ideally suited to such studies due to its relatively high yields. Hydropyrolysis of the Murchison macromolecular material successfully releases significant amounts of high molecular weight PAH including phenanthrene, carbazole, fluoranthene, pyrene, chrysene, perylene, benzoperylene and coronene units with varying degrees of alklyation. Analysis of both the products and residue from hydropyrolysis reveals that the meteoritic organic network contains both labile (pyrolysable) and refractory (nonpyrolysable) fractions. Comparisons of hydropyrolysis yields of Murchison macromolecular materials with those from terrestrial coals indicate that the refractory component probably consists of a network dominated by at least five- or six-ring PAH units cross-linked together.

Sephton, M. A.; Love, G. D.; Watson, J. S.; Verchovsky, A. B.; Wright, I. P.; Snape, C. E.; Gilmour, I.

2004-03-01

47

Macromolecular Crystallization in Microgravity  

NASA Technical Reports Server (NTRS)

The key concepts that attracted crystal growers, macromolecular or solid state, to microgravity research is that density difference fluid flows and sedimentation of the growing crystals are greatly reduced. Thus, defects and flaws in the crystals can be reduced, even eliminated, and crystal volume can be increased. Macromolecular crystallography differs from the field of crystalline semiconductors. For the latter, crystals are harnessed for their electrical behaviors. A crystal of a biological macromolecule is used instead for diffraction experiments (X-ray or neutron) to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal of a biological macromolecule then the more molecular structure detail that can be extracted. This structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences with major potential in understanding disease pathologies. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry, and mathematics meet to enable insight to the basic fundamentals of life. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment, and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyze the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural advances. Finally, limitations and alternatives to microgravity and future directions for this research are covered.

Snell, Edward H.; Helliwell, John R.

2004-01-01

48

Apparatus for the Study of the Dielectric Properties of Macromolecular Solutions under Flow  

Microsoft Academic Search

Some solutions show a change in value of their dielectric constant and specific conductance when subjected to shearing stresses produced by a velocity gradient established within them. A detailed account is given of an apparatus which has been used for studying this effect. The solution to be investigated is placed in the annular space between two concentric cylinders. The gap

H. G. Jerrard; T. A. Fisher; B. A. W. Simmons

1960-01-01

49

Effects of macromolecular crowding on nuclear size.  

PubMed

The concentration of macromolecules inside cells is high, and the resultant crowding of cytoplasm can be expected to affect many interactions involving macromolecular assemblies. Here, we have examined the effect of solute size and concentration on nuclear volume in saponin-permeabilized macrophages. Nuclei swelled in the presence of small solutes and shrank reversibly in the presence of larger permeant solutes. Remarkably, the smallest solutes capable of shrinking the nucleus were not excluded by the pores in the nuclear envelope. Indeed, nuclei shrank in the presence of such solutes even after the nuclear envelope had been sheared mechanically or permeabilized with detergent. Nuclei extracted with 1% Triton X-100 shrank in the presence of very high concentrations of small solute molecules (30% w/v) as well as in lower concentrations of larger solutes. Consistent with a macromolecular crowding effect, changes in nuclear volume were dependent on solute size and not simply dependent on the colligative properties of solutes or the exclusion of solutes by the nuclear envelope. Solute size-dependent changes in nuclear volume were independent of the chemical nature of the solutes and of the activity of the ions in the buffer. Together, these observations indicate that high concentrations of macromolecules such as those found inside cells can influence the size of the nucleus by directly affecting nuclear structure. PMID:7537686

Rosania, G R; Swanson, J A

1995-05-01

50

Study of the Development of the Mouse Thoracic Aorta Three-Dimensional Macromolecular Structure using Two-Photon Microscopy.  

PubMed

Using the intrinsic optical properties of collagen and elastin, two-photon microscopy was applied to evaluate the three-dimensional (3D) macromolecular structural development of the mouse thoracic aorta from birth to 60 days old. Baseline development was established in the Scavenger Receptor Class B Type I-Deficient, Hypomorphic Apolipoprotein ER61 (SR-BI KO/ApoeR61(h/h)) mouse in preparation for modeling atherosclerosis. Precise dissection enabled direct observation of the artery wall in situ. En-face, optical sectioning of the aorta provided a novel assessment of the macromolecular structural development. During aortic development, the undulating lamellar elastin layers compressed consistent with the increases in mean aortic pressure with age. In parallel, a net increase in overall wall thickness (p<0.05, in day 60 compared with day 1 mice) occurred with age whereas the ratio of the tunicas adventitia and media to full aortic thickness remained nearly constant across age groups (~1:2.6, respectively). Histochemical analyses by brightfield microscopy and ultrastructure validated structural proteins and lipid deposition findings derived from two-photon microscopy. Development was associated with decreased decorin but not biglycan proteoglycan expression. This non-destructive 3D in situ approach revealed the aortic wall microstructure development. Coupling this approach with the intrinsic optical properties of the macromolecules may provide unique vascular wall 3D structure in many pathological conditions, including aortic atherosclerosis, dissections and aneurysms. PMID:25362141

Zadrozny, Leah M; Neufeld, Edward B; Lucotte, Bertrand M; Connelly, Patricia S; Yu, Zu-Xi; Dao, Lam; Hsu, Li-Yueh; Balaban, Robert S

2015-01-01

51

Hierarchical amplification of macromolecular helicity of dynamic helical poly(phenylacetylene)s composed of chiral and achiral phenylacetylenes in dilute solution, liquid crystal, and two-dimensional crystal.  

PubMed

Optically active poly(phenylacetylene) copolymers consisting of optically active and achiral phenylacetylenes bearing L-alanine decyl esters (1L) and 2-aminoisobutylic acid decyl esters (Aib) as the pendant groups (poly(1L(m)-co-Aib(n))) with various compositions were synthesized by the copolymerization of the optically active 1L with achiral Aib using a rhodium catalyst, and their chiral amplification of the macromolecular helicity in a dilute solution, a lyotropic liquid crystalline (LC) state, and a two-dimensional (2D) crystal on the substrate was investigated by measuring the circular dichroism of the copolymers, mesoscopic cholesteric twist in the LC state (cholesteric helical pitch), and high-resolution atomic force microscopy (AFM) images of the self-assembled 2D helix-bundles of the copolymer chains. We found that the macromolecular helicity of poly(1L(m)-co-Aib(n))s could be hierarchically amplified in the order of the dilute solution, LC state, and 2D crystal. In sharp contrast, almost no chiral amplification of the macromolecular helicity was observed for the homopolymer mixtures of 1L and Aib in the LC state and 2D crystal on graphite. PMID:21141965

Ohsawa, Sousuke; Sakurai, Shin-ichiro; Nagai, Kanji; Banno, Motonori; Maeda, Katsuhiro; Kumaki, Jiro; Yashima, Eiji

2011-01-12

52

Complexation of Statins with ?-Cyclodextrin in Solutions of Small Molecular Additives and Macromolecular Colloids  

NASA Astrophysics Data System (ADS)

The solubility of lovastatin and simvastatin (inevitable drugs in the management of cardiovascular diseases) was studied by phase-solubility measurements in multicomponent colloidal and non-colloidal media. Complexation in aqueous solutions of the highly lipophilic statins with ?-cyclodextrin (?-CD) in the absence and the presence of dissolved polyvinyl pyrrolidone, its monomeric compound, tartaric acid and urea, respectively, were investigated. For the characterization of the CD-statin inclusion complexes, stability constants for the associates have been calculated.

Süle, András; Csempesz, Ferenc

53

NMR (Nuclear Magnetic Resonance) and macromolecular migration in a melt or in concentrated solutions  

NASA Technical Reports Server (NTRS)

The purpose of this paper is to analyze the migration process of long polymer molecules in a melt or in concentrated solutions as it may be observed from the dynamics of the transverse magnetization of nuclear spins linked to these chains. The low frequency viscoelastic relaxation of polymer systems is known to be mainly controlled by the mechanism of dissociation of topological constraints excited on chains and which are called entanglements. This mechanism exhibits a strong dependence upon the chain molecular weight. These topological constraints also govern the diffusion process of polymer chains. So, the accurate description of the diffusion motion of a chain may be a convenient way to characterize disentanglement processes necessarily involved in any model proposed to explain viscoelastic effects.

Addad, J. P. C.

1983-01-01

54

Studying macromolecular solutions without wall effects by stroboscopic small-angle x-ray scattering  

NASA Astrophysics Data System (ADS)

Small-angle x-ray scattering patterns have been collected stroboscopically from ballistic microdrops of cytochrome C protein solution. The microdrops, measuring around 80 ?m diameter (˜268pl), were generated by a drop-on-demand system and traveled at approximately 1.7 m/s through a 3 ?m synchrotron radiation beam. The scattering patterns were accumulated on a pixel detector, which was activated for a few microseconds during the transit time of each microdrop through the microbeam. The stability of the microdrop sequence allowed observing interface scattering from HCl buffer microdrops. The small-angle x-ray scattering data provide information on the protein conformation free of physical boundaries.

Graceffa, Rita; Burghammer, Manfred; Davies, Richard J.; Ponchut, Cyril; Riekel, Christian

2009-02-01

55

Teaching structure: student use of software tools for understanding macromolecular structure in an undergraduate biochemistry course.  

PubMed

Because understanding the structure of biological macromolecules is critical to understanding their function, students of biochemistry should become familiar not only with viewing, but also with generating and manipulating structural representations. We report a strategy from a one-semester undergraduate biochemistry course to integrate use of structural representation tools into both laboratory and homework activities. First, early in the course we introduce the use of readily available open-source software for visualizing protein structure, coincident with modules on amino acid and peptide bond properties. Second, we use these same software tools in lectures and incorporate images and other structure representations in homework tasks. Third, we require a capstone project in which teams of students examine a protein-nucleic acid complex and then use the software tools to illustrate for their classmates the salient features of the structure, relating how the structure helps explain biological function. To ensure engagement with a range of software and database features, we generated a detailed template file that can be used to explore any structure, and that guides students through specific applications of many of the software tools. In presentations, students demonstrate that they are successfully interpreting structural information, and using representations to illustrate particular points relevant to function. Thus, over the semester students integrate information about structural features of biological macromolecules into the larger discussion of the chemical basis of function. Together these assignments provide an accessible introduction to structural representation tools, allowing students to add these methods to their biochemical toolboxes early in their scientific development. PMID:24019219

Jaswal, Sheila S; O'Hara, Patricia B; Williamson, Patrick L; Springer, Amy L

2013-01-01

56

Teaching Structure: Student Use of Software Tools for Understanding Macromolecular Structure in an Undergraduate Biochemistry Course  

ERIC Educational Resources Information Center

Because understanding the structure of biological macromolecules is critical to understanding their function, students of biochemistry should become familiar not only with viewing, but also with generating and manipulating structural representations. We report a strategy from a one-semester undergraduate biochemistry course to integrate use of…

Jaswal, Sheila S.; O'Hara, Patricia B.; Williamson, Patrick L.; Springer, Amy L.

2013-01-01

57

Macromolecular Structure Description: This course covers the principles of protein and nucleic acid structure, stability  

E-print Network

and nucleic acid structure, stability and dynamics. Topics will include interactions, conformations, forces of Biopolymers Amino Acids The Peptide Bond Protein Rotamers: Ramachandran plots The Nucleic Acid Bases The Nucleic Acid Backbone Nucleic Acid Rotamers Introduction to PYMOL: visualization software Introduction

Sherrill, David

58

Structure, Vol. 13, 463471, March, 2005, 2005 Elsevier Ltd All rights reserved. DOI 10.1016/j.str.2005.02.004 Compressed Representations of Macromolecular  

E-print Network

manipulation hasDepartment of Computer Sciences and Institute for Computational and Engineering Sciences been understanding posed for macromolecular structures and their proper- of diseases such as cancer and other metabolic disor- ties. Molecular surfaces, approximating implicit solva- ders. Today, hybrid experimental

Texas at Austin, University of

59

Single-step antibody-based affinity cryo-electron microscopy for imaging and structural analysis of macromolecular assemblies.  

PubMed

Single particle cryo-electron microscopy (cryo-EM) is an emerging powerful tool for structural studies of macromolecular assemblies (i.e., protein complexes and viruses). Although single particle cryo-EM requires less concentrated and smaller amounts of samples than X-ray crystallography, it remains challenging to study specimens that are low-abundance, low-yield, or short-lived. The recent development of affinity grid techniques can potentially further extend single particle cryo-EM to these challenging samples by combining sample purification and cryo-EM grid preparation into a single step. Here we report a new design of affinity cryo-EM approach, cryo-SPIEM, that applies a traditional pathogen diagnosis tool Solid Phase Immune Electron Microscopy (SPIEM) to the single particle cryo-EM method. This approach provides an alternative, largely simplified and easier to use affinity grid that directly works with most native macromolecular complexes with established antibodies, and enables cryo-EM studies of native samples directly from cell cultures. In the present work, we extensively tested the feasibility of cryo-SPIEM with multiple samples including those of high or low molecular weight, macromolecules with low or high symmetry, His-tagged or native particles, and high- or low-yield macromolecules. Results for all these samples (non-purified His-tagged bacteriophage T7, His-tagged Escherichiacoli ribosomes, native Sindbis virus, and purified but low-concentration native Tulane virus) demonstrated the capability of cryo-SPIEM approach in specifically trapping and concentrating target particles on TEM grids with minimal view constraints for cryo-EM imaging and determination of 3D structures. PMID:24780590

Yu, Guimei; Vago, Frank; Zhang, Dongsheng; Snyder, Jonathan E; Yan, Rui; Zhang, Ci; Benjamin, Christopher; Jiang, Xi; Kuhn, Richard J; Serwer, Philip; Thompson, David H; Jiang, Wen

2014-07-01

60

Neutron Spectroscopy as a Probe of Macromolecular Structure and Dynamics under Extreme Spatial Confinement  

NASA Astrophysics Data System (ADS)

We illustrate the use of high-resolution neutron spectroscopy to explore the extreme spatial confinement of soft matter in nanostructured materials. Two well-defined limits are considered, involving either intercalation or interfacial adsorption of the ubiquitous polymer poly(ethylene oxide) in graphite-oxide-based hosts. Vibrational modes associated with the confined macromolecular phase undergo dramatic changes over a broad range of energy transfers, from those associated with intermolecular modes in the Terahertz frequency range (1 THz = 33 cm?1), to those characteristic of strong chemical bonds above 2000 cm?1. We also consider the effects of polymer chain size and chemical composition of the host material. Variation of the degree of oxidation and exfoliation of graphite oxide leads to two distinct cases, namely: (i) subnanometer two-dimensional confinement; and (ii) surface immobilization. Case (i) is characterised by significant changes to conformational and collective vibrational modes of the polymer as a consequence of a preferentially planar trans-trans-trans chain conformation, whereas case (ii) leads to a substantial increase in the population of gauche conformers. Macroscopically, case (i) translates into the complete suppression of crystallization and glassy behaviour. In contrast, case (ii) exhibits well-defined glass and melting transitions associated with the confined phase, yet at significantly lower temperatures than those of the bulk.

Barroso-Bujans, F.; Fernandez-Alonso, F.; Colmenero, J.

2014-11-01

61

Online Macromolecular Museum  

NSDL National Science Digital Library

As the creators of the Online Macromolecular Museum (OMM) explain, macromolecules are "scientific objects in much the same sense as fossil bones or dried specimens: they can be archived, studied, and displayed in aesthetically pleasing, educational exhibits." OMM is a valuable resource for visualizing structures involved in cellular processes, providing virtual galleries devoted to catalysis, membrane biology, ribonucleoproteins, DNA/RNA polymerization, and much more. Each gallery contains interactive tutorials, which are fun to explore even if you're not in the mood to actually learn anything. OMM is maintained by David Marcey at California Lutheran University.

62

Chemical composition and structural features of the macromolecular components of Hibiscus cannabinus grown in Portugal  

Microsoft Academic Search

Different morphological regions of Hibiscus cannabinus plants grown in Portugal were submitted to chemical composition studies. General chemical composition was determined by established methods. The polysaccharides were fractionated by successive extractions of holocellulose with aqueous KOH solutions. The sugar composition was determined by hydrolysis of polysaccharides followed by gas chromatography (GC) analysis of neutral sugars and spectrophotometric determination of uronic

C. Pascoal Neto; A. Seca; D. Fradinho; M. A. Coimbra; F. Domingues; D. Evtuguin; A. Silvestre; J. A. S. Cavaleiro

1996-01-01

63

Macromolecular Structure Modeling from 3DEM Using VOLROVER 2.01  

E-print Network

for 3DEM structure identification and model-based refinement developed by our research group research groups. The comparisons show that our software is capable of segmenting relatively accurate-Portugal-Colab project. #12;2 1 Introduction Humans have made a great deal of progress in revealing the structures

Texas at Austin, University of

64

Avoidable errors in deposited macromolecular structures: an impediment to efficient data mining.  

PubMed

Whereas the vast majority of the more than 85?000 crystal structures of macromolecules currently deposited in the Protein Data Bank are of high quality, some suffer from a variety of imperfections. Although this fact has been pointed out in the past, it is still worth periodic updates so that the metadata obtained by global analysis of the available crystal structures, as well as the utilization of the individual structures for tasks such as drug design, should be based on only the most reliable data. Here, selected abnormal deposited structures have been analysed based on the Bayesian reasoning that the correctness of a model must be judged against both the primary evidence as well as prior knowledge. These structures, as well as information gained from the corresponding publications (if available), have emphasized some of the most prevalent types of common problems. The errors are often perfect illustrations of the nature of human cognition, which is frequently influenced by preconceptions that may lead to fanciful results in the absence of proper validation. Common errors can be traced to negligence and a lack of rigorous verification of the models against electron density, creation of non-parsimonious models, generation of improbable numbers, application of incorrect symmetry, illogical presentation of the results, or violation of the rules of chemistry and physics. Paying more attention to such problems, not only in the final validation stages but during the structure-determination process as well, is necessary not only in order to maintain the highest possible quality of the structural repositories and databases but most of all to provide a solid basis for subsequent studies, including large-scale data-mining projects. For many scientists PDB deposition is a rather infrequent event, so the need for proper training and supervision is emphasized, as well as the need for constant alertness of reason and critical judgment as absolutely necessary safeguarding measures against such problems. Ways of identifying more problematic structures are suggested so that their users may be properly alerted to their possible shortcomings. PMID:25075337

Dauter, Zbigniew; Wlodawer, Alexander; Minor, Wladek; Jaskolski, Mariusz; Rupp, Bernhard

2014-05-01

65

Avoidable errors in deposited macromolecular structures: an impediment to efficient data mining  

PubMed Central

Whereas the vast majority of the more than 85?000 crystal structures of macromolecules currently deposited in the Protein Data Bank are of high quality, some suffer from a variety of imperfections. Although this fact has been pointed out in the past, it is still worth periodic updates so that the metadata obtained by global analysis of the available crystal structures, as well as the utilization of the individual structures for tasks such as drug design, should be based on only the most reliable data. Here, selected abnormal deposited structures have been analysed based on the Bayesian reasoning that the correctness of a model must be judged against both the primary evidence as well as prior knowledge. These structures, as well as information gained from the corresponding publications (if available), have emphasized some of the most prevalent types of common problems. The errors are often perfect illustrations of the nature of human cognition, which is frequently influenced by preconceptions that may lead to fanciful results in the absence of proper validation. Common errors can be traced to negligence and a lack of rigorous verification of the models against electron density, creation of non-parsimonious models, generation of improbable numbers, application of incorrect symmetry, illogical presentation of the results, or violation of the rules of chemistry and physics. Paying more attention to such problems, not only in the final validation stages but during the structure-determination process as well, is necessary not only in order to maintain the highest possible quality of the structural repositories and databases but most of all to provide a solid basis for subsequent studies, including large-scale data-mining projects. For many scientists PDB deposition is a rather infrequent event, so the need for proper training and supervision is emphasized, as well as the need for constant alertness of reason and critical judgment as absolutely necessary safeguarding measures against such problems. Ways of identifying more problematic structures are suggested so that their users may be properly alerted to their possible shortcomings. PMID:25075337

Dauter, Zbigniew; Wlodawer, Alexander; Minor, Wladek; Jaskolski, Mariusz; Rupp, Bernhard

2014-01-01

66

Understanding Structural Stability of Pharmaceutically Relevant Macromolecular Complexes: A Biophysical and Biochemical Approach  

E-print Network

-based EPDs. v Dedicated to: My parents, Mansour & Farah Esfandiary vi Acknowledgements I would first like to thank my graduate advisor, Russell Middaugh. Russ you... diagram? (EPD approach) utilizes advanced algebraic procedures to integrate a large library of data obtained from a variety of biophysical techniques into an easy-to-interpret color coded map to provide a global picture of protein structural alterations...

Esfandiary, Reza

2009-08-10

67

Improving the accuracy of macromolecular structure refinement at 7 Å resolution  

PubMed Central

SUMMARY In X-ray crystallography, molecular replacement and subsequent refinement is challenging at low resolution. We compared refinement methods using synchrotron diffraction data of photosystem I at 7.4 Å resolution, starting from different initial models with increasing deviations from the known high-resolution structure. Standard refinement spoiled the initial models moving them further away from the true structure and leading to high Rfree-values. In contrast, DEN-refinement improved even the most distant starting model as judged by Rfree, atomic root-mean-square differences to the true structure, significance of features not included in the initial model, and connectivity of electron density. The best protocol was DEN-refinement with initial segmented rigid-body refinement. For the most distant initial model, the fraction of atoms within 2 Å of the true structure improved from 24% to 60%. We also found a significant correlation between Rfree-values and the accuracy of the model, suggesting that Rfree is useful even at low resolution. PMID:22681901

Brunger, Axel T.; Adams, Paul D.; Fromme, Petra; Fromme, Raimund; Levitt, Michael; Schröder, Gunnar F.

2012-01-01

68

Cooperative macromolecular device revealed by meta-analysis of static and time-resolved structures  

SciTech Connect

Here we present a meta-analysis of a large collection of static structures of a protein in the Protein Data Bank in order to extract the progression of structural events during protein function. We apply this strategy to the homodimeric hemoglobin HbI from Scapharca inaequivalvis. We derive a simple dynamic model describing how binding of the first ligand in one of the two chemically identical subunits facilitates a second binding event in the other partner subunit. The results of our ultrafast time-resolved crystallographic studies support this model. We demonstrate that HbI functions like a homodimeric mechanical device, such as pliers or scissors. Ligand-induced motion originating in one subunit is transmitted to the other via conserved pivot points, where the E and F' helices from two partner subunits are 'bolted' together to form a stable dimer interface permitting slight relative rotation but preventing sliding.

Ren, Zhong; Š rajer, Vukica; Knapp, James E.; Royer, Jr., William E. (Mercer); (UMASS, MED); (UC)

2013-04-08

69

Cooperative macromolecular device revealed by meta-analysis of static and time-resolved structures.  

PubMed

Here we present a meta-analysis of a large collection of static structures of a protein in the Protein Data Bank in order to extract the progression of structural events during protein function. We apply this strategy to the homodimeric hemoglobin HbI from Scapharca inaequivalvis. We derive a simple dynamic model describing how binding of the first ligand in one of the two chemically identical subunits facilitates a second binding event in the other partner subunit. The results of our ultrafast time-resolved crystallographic studies support this model. We demonstrate that HbI functions like a homodimeric mechanical device, such as pliers or scissors. Ligand-induced motion originating in one subunit is transmitted to the other via conserved pivot points, where the E and F' helices from two partner subunits are "bolted" together to form a stable dimer interface permitting slight relative rotation but preventing sliding. PMID:22171006

Ren, Zhong; Srajer, Vukica; Knapp, James E; Royer, William E

2012-01-01

70

Cooperative macromolecular device revealed by meta-analysis of static and time-resolved structures  

PubMed Central

Here we present a meta-analysis of a large collection of static structures of a protein in the Protein Data Bank in order to extract the progression of structural events during protein function. We apply this strategy to the homodimeric hemoglobin HbI from Scapharca inaequivalvis. We derive a simple dynamic model describing how binding of the first ligand in one of the two chemically identical subunits facilitates a second binding event in the other partner subunit. The results of our ultrafast time-resolved crystallographic studies support this model. We demonstrate that HbI functions like a homodimeric mechanical device, such as pliers or scissors. Ligand-induced motion originating in one subunit is transmitted to the other via conserved pivot points, where the E and F? helices from two partner subunits are “bolted” together to form a stable dimer interface permitting slight relative rotation but preventing sliding. PMID:22171006

Ren, Zhong; Šrajer, Vukica; Knapp, James E.; Royer, William E.

2012-01-01

71

Macromolecular organisation of recombinant Yersinia pestis F1 antigen and the effect of structure on immunogenicity  

Microsoft Academic Search

Yersinia pestis, the causative organism of plague, produces a capsular protein (fraction 1 or F1 antigen) that is one of the major virulence factors of the bacterium. We report here the production, structural and immunological characterisation of a recombinant F1 antigen (rF1). The rF1 was purified by ammonium sulfate fractionation followed by FPLC Superose gel filtration chromatography. Using FPLC gel

Julie Miller; E. Diane Williamson; Jeremy H Lakey; Martin J Pearce; Steven M Jones; Richard W Titball

1998-01-01

72

Macromolecular recognition: Structural aspects of the origin of the genetic system  

NASA Technical Reports Server (NTRS)

Theoretical simulation of prebiotic chemical processes is an invaluable tool for probing the phenomenon of the evolution of life. Using computational and modeling techniques and guided by analogies from present day systems, we seek to understand the emergence of the genetic apparatus, enzymatic catalysis and protein synthesis under prebiotic conditions. Modeling of the ancestral aminoacyl-tRNA-synthetases (aRS) may provide important clues to the emergence of the genetic code and the protein synthetic machinery. The minimal structural requirements for the catalysis of tRNA aminoacylation are being explored. A formation of an aminoacyl adenylate was studied in the framework of ab initio molecular orbital theory. The role of individual residues in the vicinity of the TyrRS active site was examined, and the effect of all possible amino acids substitutions near the active site was examined. A formation of aminoacyl tRNA was studied by the molecular modeling system SYBYL with the high resolution crystallographic structures of the present day tRNA, aRS's complexes. The ultimate goal is to propose a simple RNA segment that is small enough to be build in the primordial chemical environment but maintains the specificity and catalytic activity of the contemporary RNA enzyme. To understand the mechanism of ribozyme catalyzed reactions, ab initio and semi-empirical (ZINDO) programs were used to investigate the reaction path of transphosphorylation. A special emphasis was placed on the possible catalytic and structural roles played by the coordinated magnesium cation. Both the inline and adjacent mechanisms of transphosphorylation were studied. The structural characteristics of the target helices, particularly a possible role for the G-T pair, is also studied by a molecular dynamics (MD) simulation technique.

Rein, Robert; Sokalski, W. Andrzej; Barak, Dov; Luo, Ning; Zielinski, Theresa Julia; Shibata, Masayuki

1991-01-01

73

MolProbity : all-atom structure validation for macromolecular crystallography  

Microsoft Academic Search

MolProbity is a structure-validation web service that provides broad-spectrum solidly based evaluation of model quality at both the global and local levels for both proteins and nucleic acids. It relies heavily on the power and sensitivity provided by optimized hydrogen placement and all-atom contact analysis, complemented by updated versions of covalent-geometry and torsion-angle criteria. Some of the local corrections can

Vincent B. Chen; W. Bryan Arendall; Jeffrey J. Headd; Daniel A. Keedy; Robert M. Immormino; Gary J. Kapral; Laura W. Murray; David C. Richardson

2010-01-01

74

Macromolecular recognition: Structural aspects of the origin of the genetic system  

NASA Technical Reports Server (NTRS)

Theoretical simulation of prebiotic chemical processes is an invaluable tool for probing the phenomenon of evolution of life. Using computational and modeling techniques and guided by analogies from present day systems we, seek to understand the emergence of genetic apparatus, enzymatic catalysis and protein synthesis under prebiotic conditions. In one possible scenario, the RNA enzymatic reaction plays a key role in the emergence of the self-replicating and offers a clue to the onset of enzymatic catalysis prior to the existence of the protein biosynthetic machinery. Our ultimate goal is to propose a simple RNA segment which contains the specificity and catalytic activity of the contemporary RNA enzyme and which could emerge in a primordial chemical environment. To understand the mechanism of ribozyme catalyzed reactions, ab initio and semi-empirical (ZINDO) programs were used to investigate the reaction path of transphosphorylation. A special emphasis was placed on the possible catalytic and structural roles played by the coordinated magnesium cation. Both the inline and adjacent mechanisms of transphosphorylation have been studied. Another important aspect of this reaction is the identity of the functional groups which are essential for the acid base catalysis. The structural characteristics of the target helices, particularly a possible role of G center dot T pair, is under examination by molecular dynamics (MD) simulation technique. Modeling of the ancestral aminoacyl-tRNA synthetases (aRS) may provide important clues to the emergence of the genetic code and the protein synthetic machinery. Assuming that the catalytic function evolved before the elements of specific recognition of a particular amino acid, we are exploring the minimal structural requirements for the catalysis of tRNA aminoacylation. The molecular modeling system SYBYL was used for this study based on the high resolution crystallographic structures of the present day tyrosyl-adenylate:tyrRS and tRNA(Gln): ATP:glnRS complexes. The trinucleotide CCA of the 3'-end tRNA is placed into the active site pocket of tyrRS, based on the scheme of interaction between tRNA(Gln) and glnRS, and upon the stereochemistry of the tyrRS:tRNA:Tyr-AMP transition state. This provides a model of the non-specific recognition of a tRNA's 3'-end by an aRS, which might be similar to that of the ancestral aRS's. In the next step, modeling of the rest of the acceptor stem of tRNA (Tyr) with tyrRS is carried out.

Rein, Robert; Barak, Dov; Luo, Ning; Zielinski, Theresa Julia; Shibata, Masayuki

1991-01-01

75

Structure and property relations of macromolecular self-assemblies at interfaces  

NASA Astrophysics Data System (ADS)

Hydrophilic polymer chains, poly(ethylene glycol) (PEG), are attached to glass surfaces by silylation of the silanol groups on glass surfaces with the omega-(methoxyl terminated PEG) trimethoxysilanes. These tethered polymer chains resemble the self-assembled monolayers (SAMs) of PEG, which exhibit excellent biocompatibility and provide a model system for studying the interactions of proteins with polymer surfaces. The low molecular weight PEGs tend to extend, forming a brush-like monolayer, whereas the longer polymer chains tend to interpenetrate each other, forming a mushroom-like PEG monolayer at the interface. Interactions between a plasma protein, bovine serum albumin, and the PEG-SAMs are investigated in terms of protein adsorption and diffusion on the surfaces by the technique of fluorescence recovery after photobleaching (FRAP). The diffusion and aggregation behaviors of the protein on the two monolayers are found to be quite different despite the similarities in adsorption and desorption behaviors. The results are analyzed with a hypothesis of the hydrated surface dynamics. A method of covalently bonding phospholipid molecules to silica substrates followed by loading with free phospholipids is demonstrated to form well organized and stable phospholipid self-assembled monolayers. Surfaces of such SAMs structurally mimic the aqueous sides of phospholipid bilayer membranes. The dynamics of phospholipids and an adsorbed protein, lipase, in the SAMs are probed with FRAP, in terms of lateral diffusion of both phospholipids and protein molecules. The esterase activity of lipase on the SAM surfaces is confirmed by the hydrolysis reaction of a substrate, umbelliferone stearate, showing such lipid SAMs posess biomembrane functionality in terms of interfacial activation of the membranous enzymes. Dynamics of polyethylene oxide and polypropylene oxide tri-block copolymers, PEO-PPO-PEO and PPO-PEO-PPO, at the air/water interface upon thermal stimulation is studied by surface light scattering, in terms of the dynamic surface tension changes in response to a temperature jump. The characteristic of the surface tension relaxation is found to be highly related to the molecular structure and concentration of the copolymers at the interface.

Yang, Zhihao

76

Harvesting and cryo-cooling crystals of membrane proteins grown in lipidic mesophases for structure determination by macromolecular crystallography.  

PubMed

An important route to understanding how proteins function at a mechanistic level is to have the structure of the target protein available, ideally at atomic resolution. Presently, there is only one way to capture such information as applied to integral membrane proteins (Figure 1), and the complexes they form, and that method is macromolecular X-ray crystallography (MX). To do MX diffraction quality crystals are needed which, in the case of membrane proteins, do not form readily. A method for crystallizing membrane proteins that involves the use of lipidic mesophases, specifically the cubic and sponge phases(1-5), has gained considerable attention of late due to the successes it has had in the G protein-coupled receptor field(6-21) (www.mpdb.tcd.ie). However, the method, henceforth referred to as the in meso or lipidic cubic phase method, comes with its own technical challenges. These arise, in part, due to the generally viscous and sticky nature of the lipidic mesophase in which the crystals, which are often micro-crystals, grow. Manipulating crystals becomes difficult as a result and particularly so during harvesting(22,23). Problems arise too at the step that precedes harvesting which requires that the glass sandwich plates in which the crystals grow (Figure 2)(24,25) are opened to expose the mesophase bolus, and the crystals therein, for harvesting, cryo-cooling and eventual X-ray diffraction data collection. The cubic and sponge mesophase variants (Figure 3) from which crystals must be harvested have profoundly different rheologies(4,26). The cubic phase is viscous and sticky akin to a thick toothpaste. By contrast, the sponge phase is more fluid with a distinct tendency to flow. Accordingly, different approaches for opening crystallization wells containing crystals growing in the cubic and the sponge phase are called for as indeed different methods are required for harvesting crystals from the two mesophase types. Protocols for doing just that have been refined and implemented in the Membrane Structural and Functional Biology (MS&FB) Group, and are described in detail in this JoVE article (Figure 4). Examples are given of situations where crystals are successfully harvested and cryo-cooled. We also provide examples of cases where problems arise that lead to the irretrievable loss of crystals and describe how these problems can be avoided. In this article the Viewer is provided with step-by-step instructions for opening glass sandwich crystallization wells, for harvesting and for cryo-cooling crystals of membrane proteins growing in cubic and in sponge phases. PMID:22971942

Li, Dianfan; Boland, Coilín; Aragao, David; Walsh, Kilian; Caffrey, Martin

2012-01-01

77

Visualizing Macromolecular Complexes with In Situ Liquid Scanning Transmission Electron Microscopy  

SciTech Connect

A central focus of biological research is understanding the structure/function relationship of macromolecular protein complexes. Yet conventional transmission electron microscopy techniques are limited to static observations. Here we present the first direct images of purified macromolecular protein complexes using in situ liquid scanning transmission electron microscopy. Our results establish the capability of this technique for visualizing the interface between biology and nanotechnology with high fidelity while also probing the interactions of biomolecules within solution. This method represents an important advancement towards allowing future high-resolution observations of biological processes and conformational dynamics in real-time.

Evans, James E.; Jungjohann, K. L.; Wong, Peony C. K.; Chiu, Po-Lin; Dutrow, Gavin H.; Arslan, Ilke; Browning, Nigel D.

2012-11-01

78

What Macromolecular Crowding Can Do to a Protein  

PubMed Central

The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area. PMID:25514413

Kuznetsova, Irina M.; Turoverov, Konstantin K.; Uversky, Vladimir N.

2014-01-01

79

Complex structures – smart solutions  

PubMed Central

The siliceous skeletal elements of the sponges, the spicules, represent one of the very few examples from where the molecule toolkit required for the formation of an extracellular mineral-based skeleton, has been elucidated. The distinguished feature of the inorganic matrix, the bio-silica, is its enzymatic synthesis mediated by silicatein. Ortho-silicate undergoes in the presence of silicatein a polycondensation reaction and forms bio-silica under release of reaction water. The protein silicatein aggregates non-covalently to larger filaments, a process that is stabilized by the silicatein-associated protein, silintaphin-1. These structured clusters form the axial filament that is located in the center of the spicules, the axial canal. Surprisingly it has now been found that the initial axial orientation, in which the spicules grow, is guided by cell processes through evagination. The approximately two µm wide cell extensions release silicatein that forms the first organic axial filament, which then synthesizes the inner core of the siliceous spicule rods. In parallel, the radial growth of the spicules is controlled by a telescopic arrangement of organic layers, into which bio-silica and ortho-silicate are deposited. Hence, the formation of a mature siliceous spicule is completed by a centrifugal accretion of bio-silica mediated by the silicatein in the axial filament, and a centripetal bio-silica deposition catalyzed by the extra-spicular silicatein. Finally this contribution highlights that for the ultimate determination of the spicule shapes, their species-specific morphologies, bio-silica hardens during a process which removes reaction water. The data presented can also provide new blueprints for the fabrication of novel biomaterials for biomedical applications.  PMID:22446527

2011-01-01

80

Transmucosal macromolecular drug delivery  

Microsoft Academic Search

Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and\\/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, the use of nanoparticulate

C. Prego; M. García; D. Torres; M. J. Alonso

2005-01-01

81

Vibron transport in macromolecular chains  

E-print Network

We study the hopping mechanism of the vibron excitation transport in the simple 1D model of biological macromolecular chains. We supposed that the vibron interaction with thermal oscillations of the macromolecular structural elements will result in vibron self -trapping, and the formation of the partial dressed vibron state. With use of the modified Holstein polaron model, we calculate vibron diffusivity in dependence of the basic system parameters and temperature. We obtain that the vibron diffusivity smoothly decreases in non adiabatic limit when the strength of the vibron-phonon coupling grows. However this dependence becomes by discontinuous one in case of growth of the adiabaticity of the system. The value of the critical point depends of the system temperature, and at room temperatures it belongs to the low or intermediate coupling regime. We discuss an application of these results to study of vibron transport to 3D bundles of such macromolecules chains considering it as polymer nanorods and to 2D polymer films organized from such macromolecules.

D. ?evizovi?; Z. Ivic.; S. Galovi?; A. Chizhov A.; A. Reshetnyak

2014-12-16

82

ACHESYM: an algorithm and server for standardized placement of macromolecular models in the unit cell.  

PubMed

Despite the existence of numerous useful conventions in structural crystallography, for example for the choice of the asymmetric part of the unit cell or of reciprocal space, surprisingly no standards are in use for the placement of the molecular model in the unit cell, often leading to inconsistencies or confusion. A conceptual solution for this problem has been proposed for macromolecular crystal structures based on the idea of the anti-Cheshire unit cell. Here, a program and server (called ACHESYM; http://achesym.ibch.poznan.pl) are presented for the practical implementation of this concept. In addition, the first task of ACHESYM is to find an optimal (compact) macromolecular assembly if more than one polymer chain exists. ACHESYM processes PDB (atomic parameters and TLS matrices) and mmCIF (diffraction data) input files to produce a new coordinate set and to reindex the reflections and modify their phases, if necessary. PMID:25478846

Kowiel, Marcin; Jaskolski, Mariusz; Dauter, Zbigniew

2014-12-01

83

Workshop on algorithms for macromolecular modeling. Final project report, June 1, 1994--May 31, 1995  

SciTech Connect

A workshop was held on algorithms and parallel implementations for macromolecular dynamics, protein folding, and structural refinement. This document contains abstracts and brief reports from that workshop.

Leimkuhler, B.; Hermans, J.; Skeel, R.D.

1995-07-01

84

Transition state structures in solution  

NASA Astrophysics Data System (ADS)

In the present paper the location of transition state structures for reactions in solution has been studied. Continuum model calculations have been carried out on the Friedel-Crafts alkylation reaction and a proton transfer through a water molecule between two oxygen atoms in formic acid. In this model the separation between the chemical system and the solvent has been introduced. On the other hand, the discrete Monte Carlo methodology has also been used to simulate the solvent effect on dissociative electron transfer processes. In this model, the hypothesis of separability is not assumed. Finally, the validity of both approaches is discussed.

Bertrán, J.; Lluch, J. M.; Gonzàlez-Lafont, A.; Dillet, V.; Pérez, V.

1995-04-01

85

Transition state structures in solution  

SciTech Connect

In the present paper the location of transition state structures for reactions in solution has been studied. Continuum model calculations have been carried out on the Friedel-Crafts alkylation reaction and a proton transfer through a water molecule between two oxygen atoms in formic acid. In this model the separation between the chemical system and the solvent has been introduced. On the other hand, the discrete Monte Carlo methodology has also been used to simulate the solvent effect on dissociative electron transfer processes. In this model, the hypothesis of separability is not assumed. Finally, the validity of both approaches is discussed.

Bertran, J.; Lluch, J. M.; Gonzalez-Lafont, A.; Dillet, V.; Perez, V. [Unitat de Quimica Fisica, Departament de Quimica. Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain)

1995-04-05

86

Working at higher magnifications in scanning electron microscopy with secondary and backscattered electrons on metal coated biological specimens and imaging macromolecular cell membrane structures.  

PubMed

Membrane structures of macromolecular dimensions were imaged with high resolution secondary electron type I (SE-I) signal contrasts on metal coated biological specimens. The quality of the surface information was strongly dependent on the signal used for microscopy and on the properties of metal films, i.e., thickness, continuity, structure and decoration effects. Films of 10 nm thickness produced so much type II electrons that identical images were obtained with the conventional SE-II and BSE-II signals. In such images, the type I SE signal was so low that only very weak contrasts were recognizable. If the films--continuous or discontinuous--were composed of large metal aggregates (gold and platinum) a strong micro-roughness contrast was produced by the type II signal. At high magnifications (100,000 x) this background signal greatly reduced the S/N ratio of the SE-I signal. A similar effect was previously shown to be produced by the type III background signal. The type II background signal minimized when continuous films of small aggregates (tantalum and chromium) were applied. SE-I contrast dominated in the image if the film thickness was limited to 1 nm. Additionally, it was found that gold and platinum decorated membrane surface structures, less than 20 nm in size, and did not reveal all the topographic information available (size, shape, orientation spacing of small surface features) but merely displayed center-to-center distances. These decoration effects were avoided and extensive topographic information was obtained through surface coating with Ta or Cr. PMID:4095499

Peters, K R

1985-01-01

87

RECENT ADVANCES IN MACROMOLECULAR HYDRODYNAMIC MODELING  

PubMed Central

The modern implementation of the boundary element method (S.R. Aragon, J. Comput. Chem. 25(2004)1191–12055) has ushered unprecedented accuracy and precision for the solution of the Stokes equations of hydrodynamics with stick boundary conditions. This article begins by reviewing computations with the program BEST of smooth surface objects such as ellipsoids, the dumbbell, and cylinders that demonstrate that the numerical solution of the integral equation formulation of hydrodynamics yields very high precision and accuracy. When BEST is used for macromolecular computations, the limiting factor becomes the definition of the molecular hydrodynamic surface and the implied effective solvation of the molecular surface. Studies on 49 different proteins, ranging in molecular weight from 9 to over 400 kDa, have shown that a model using a 1.1 A thick hydration layer describes all protein transport properties very well for the overwhelming majority of them. In addition, this data implies that the crystal structure is an excellent representation of the average solution structure for most of them. In order to investigate the origin of a handful of significant discrepancies in some multimeric proteins (over ?20% observed in the intrinsic viscosity), the technique of Molecular Dynamics simulation (MD) has been incorporated into the research program. A preliminary study of dimeric ?-chymotrypsin using approximate implicit water MD is presented. In addition I describe the successful validation of modern protein force fields, ff03 and ff99SB, for the accurate computation of solution structure in explicit water simulation by comparison of trajectory ensemble average computed transport properties with experimental measurements. This work includes small proteins such as lysozyme, ribonuclease and ubiquitin using trajectories around 10 ns duration. We have also studied a 150 kDa flexible monoclonal IgG antibody, trastuzumab, with multiple independent trajectories encompassing over 320 ns of simulation. The close agreement within experimental error of the computed and measured properties allows us to conclude that MD does produce structures typical of those in solution, and that flexible molecules can be properly described using the method of ensemble averaging over a trajectory. We review similar work on the study of a transfer RNA molecule and DNA oligomers that demonstrate that within 3% a simple uniform hydration model 1.1 A thick provides agreement with experiment for these nucleic acids. In the case of linear oligomers, the precision can be improved close to 1% by a non-uniform hydration model that hydrates mainly in the DNA grooves, in agreement with high resolution x-ray diffraction. We conclude with a vista on planned improvements for the BEST program to decrease its memory requirements and increase its speed without sacrificing accuracy. PMID:21073955

Aragon, Sergio R.

2010-01-01

88

‘Broken symmetries’ in macromolecular crystallography: phasing from unmerged data  

PubMed Central

The space-group symmetry of a crystal structure imposes a point-group symmetry on its diffraction pattern, giving rise to so-called symmetry-equivalent reflections. Instances in macromolecular crystallography are discussed in which the sym­metry in reciprocal space is broken, i.e. where symmetry-related reflections are no longer equivalent. Such a situation occurs when the sample suffers from site-specific radiation damage during the X-ray measurements. Another example of broken symmetry arises from the polarization anisotropy of anomalous scattering. In these cases, the genuine intensity differences between symmetry-related reflections can be exploited to yield phase information in the structure-solution process. In this approach, the usual separation of the data merging and phasing steps is abandoned. The data are kept unmerged down to the Harker construction, where the symmetry-breaking effects are explicitly modelled and refined and become a source of supplementary phase information. PMID:20382998

Schiltz, Marc; Bricogne, Gérard

2010-01-01

89

?-Orthogonal Pericyclic Macromolecular Photoligation.  

PubMed

A photochemical strategy enabling ?-orthogonal reactions is introduced to construct macromolecular architectures and to encode variable functional groups with site-selective precision into a single molecule by the choice of wavelength. ?-Orthogonal pericyclic reactions proceed independently of one another by the selection of functional groups that absorb light of specific wavelengths. The power of the new concept is shown by a one-pot reaction of equimolar quantities of maleimide with two polymers carrying different maleimide-reactive endgroups, that is, a photoactive diene (photoenol) and a nitrile imine (tetrazole). Under selective irradiation at ?=310-350?nm, any maleimide (or activated ene) end-capped compound reacts exclusively with the photoenol functional polymer. After complete conversion of the photoenol, subsequent irradiation at ?=270-310?nm activates the reaction of the tetrazole group with functional enes. The versatility of the approach is shown by ?-orthogonal click reactions of complex maleimides, functional enes, and polymers to the central polymer scaffold. PMID:25620295

Hiltebrandt, Kai; Pauloehrl, Thomas; Blinco, James P; Linkert, Katharina; Börner, Hans G; Barner-Kowollik, Christopher

2015-02-23

90

Significance of Wall Structure, Macromolecular Composition, and Surface Polymers to the Survival and Transport of Cryptosporidium parvum Oocysts?  

PubMed Central

The structure and composition of the oocyst wall are primary factors determining the survival and hydrologic transport of Cryptosporidium parvum oocysts outside the host. Microscopic and biochemical analyses of whole oocysts and purified oocyst walls were undertaken to better understand the inactivation kinetics and hydrologic transport of oocysts in terrestrial and aquatic environments. Results of microscopy showed an outer electron-dense layer, a translucent middle layer, two inner electron-dense layers, and a suture structure embedded in the inner electron-dense layers. Freeze-substitution showed an expanded glycocalyx layer external to the outer bilayer, and Alcian Blue staining confirmed its presence on some but not all oocysts. Biochemical analyses of purified oocyst walls revealed carbohydrate components, medium- and long-chain fatty acids, and aliphatic hydrocarbons. Purified walls contained 7.5% total protein (by the Lowry assay), with five major bands in SDS-PAGE gels. Staining of purified oocyst walls with magnesium anilinonaphthalene-8-sulfonic acid indicated the presence of hydrophobic proteins. These structural and biochemical analyses support a model of the oocyst wall that is variably impermeable and resistant to many environmental pressures. The strength and flexibility of oocyst walls appear to depend on an inner layer of glycoprotein. The temperature-dependent permeability of oocyst walls may be associated with waxy hydrocarbons in the electron-translucent layer. The complex chemistry of these layers may explain the known acid-fast staining properties of oocysts, as well as some of the survival characteristics of oocysts in terrestrial and aquatic environments. The outer glycocalyx surface layer provides immunogenicity and attachment possibilities, and its ephemeral nature may explain the variable surface properties noted in oocyst hydrologic transport studies. PMID:20097810

Jenkins, Michael B.; Eaglesham, Barbara S.; Anthony, Larry C.; Kachlany, Scott C.; Bowman, Dwight D.; Ghiorse, William C.

2010-01-01

91

Atomic-force-microscopy studies of phase separations in macromolecular systems  

NASA Astrophysics Data System (ADS)

Atomic force microscopy (AFM) has been used to visualize events arising from the formation of intervening metastable phases at the surfaces of macromolecular crystals growing from solution. Crystals investigated were of the proteins canavalin, thaumatin, lipase, xylanase, and catalase, crystals of transfer RNA, and crystals of satellite tobacco mosaic virus. Two types of aggregates were observed. The first were small, linear and branched aggregates, perhaps fractile in structure. These were incorporated into growing crystals as impurities, and they produced defects of various kinds. The second aggregate form we infer to be liquid-protein droplets which were particularly evident in freshly mixed protein-precipitant solutions. Droplets, upon sedimentation, have two possible fates. In some cases they immediately restructured as crystalline multilayer stacks whose development was guided by and contiguous with the underlying lattice. These contributed to the ordered growth of the crystal by serving as sources of growth steps. In other cases, liquid-protein droplets formed distinct microcrystals, somehow discontinuous with the underlying lattice, and these were subsequently incorporated into the growing substrate crystal with the formation of defects. Scarring experiments with the AFM tip indicated that liquid-protein droplets with the potential to rapidly crystallize were a consequence of concentration instabilities near the crystal's surfaces. The AFM study suggests that phase separation and the appearance of aggregates having limited order is a common occurrence in supersaturated macromolecular solutions such as the protein-precipitant solutions used for crystallization.

Kuznetsov, Yu. G.; Malkin, A. J.; McPherson, A.

1998-09-01

92

Protein Diffusion and Macromolecular Crowding in Thylakoid Membranes1[W  

E-print Network

Protein Diffusion and Macromolecular Crowding in Thylakoid Membranes1[W] Helmut Kirchhoff*, Silvia by chlorophyll-binding protein complexes located in the thylakoid membranes within the chloroplasts. Thylakoid membranes have a complex structure, with lateral segregation of protein complexes into distinct membrane

Allen, John F.

93

Neutron Laue macromolecular crystallography  

Microsoft Academic Search

Recent progress in neutron protein crystallography such as the use of the Laue technique and improved neutron optics and detector technologies have dramatically improved the speed and precision with which neutron protein structures can now be determined. These studies are providing unique and complementary insights on hydrogen and hydration in protein crystal structures that are not available from X-ray structures

Flora Meilleur; Dean A. A. Myles; Matthew P. Blakeley

2006-01-01

94

Significant Structure Theory Applied to Electrolyte Solution  

Microsoft Academic Search

The significant structure theory has been successfully applied to an aqueous NaCl solution. Liquid water is assumed to have a domain structure and the ions are hydrated by water molecules. The partition function is composed of the partition function for the water and that for the salt, and the excess free energy term from the Debye-Huckel theory is also added.

Jong Myung Lee; Mu Shik Jhon; Henry Eyring

1979-01-01

95

Preconditioned Parallel MLFMA Solution of Metamaterial Structures  

E-print Network

Preconditioned Parallel MLFMA Solution of Metamaterial Structures Levent Gürel, �zgür Ergül, Tahir, Bilkent, Ankara, Turkey E-mail: lgurel@bilkent.edu.tr Since metamaterials display unusual electromagnetic issue. The metamaterial structures considered in this study consist of split-ring resonators (SRRs

Gürel, Levent

96

Multiscale Macromolecular Simulation: Role of Evolving Ensembles  

PubMed Central

Multiscale analysis provides an algorithm for the efficient simulation of macromolecular assemblies. This algorithm involves the coevolution of a quasiequilibrium probability density of atomic configurations and the Langevin dynamics of spatial coarse-grained variables denoted order parameters (OPs) characterizing nanoscale system features. In practice, implementation of the probability density involves the generation of constant OP ensembles of atomic configurations. Such ensembles are used to construct thermal forces and diffusion factors that mediate the stochastic OP dynamics. Generation of all-atom ensembles at every Langevin timestep is computationally expensive. Here, multiscale computation for macromolecular systems is made more efficient by a method that self-consistently folds in ensembles of all-atom configurations constructed in an earlier step, history, of the Langevin evolution. This procedure accounts for the temporal evolution of these ensembles, accurately providing thermal forces and diffusions. It is shown that efficiency and accuracy of the OP-based simulations is increased via the integration of this historical information. Accuracy improves with the square root of the number of historical timesteps included in the calculation. As a result, CPU usage can be decreased by a factor of 3-8 without loss of accuracy. The algorithm is implemented into our existing force-field based multiscale simulation platform and demonstrated via the structural dynamics of viral capsomers. PMID:22978601

Singharoy, A.; Joshi, H.; Ortoleva, P.J.

2013-01-01

97

Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography  

PubMed Central

The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10?µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein. PMID:23897484

Foadi, James; Aller, Pierre; Alguel, Yilmaz; Cameron, Alex; Axford, Danny; Owen, Robin L.; Armour, Wes; Waterman, David G.; Iwata, So; Evans, Gwyndaf

2013-01-01

98

Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography.  

PubMed

The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10?µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein. PMID:23897484

Foadi, James; Aller, Pierre; Alguel, Yilmaz; Cameron, Alex; Axford, Danny; Owen, Robin L; Armour, Wes; Waterman, David G; Iwata, So; Evans, Gwyndaf

2013-08-01

99

Facile Preparation of a Macromolecular Benzophenone Photoinitiator  

NASA Astrophysics Data System (ADS)

Photoinitiators play important roles in the preparation of photo-cured resins. Macromolecular as well as reactive photoinitiators have attracted much attention both in industry and in academia due to the disadvantages of conventional small molecular photoinitiators such as volatility and mobility. A macromolecular benzophenone photoinitiator was designed and efficiently synthesized in this study. Hydroxyl-containing Michler's ketone was firstly synthesized in 82% yield, followed by reacting with toluene di-isocyanate (TDI) to prepare polyurethanetype macromolecular benzophenone photoinitiator.

Huang, Qinghua; Gu, Lingling; Bai, Xiongxiong; Cheng, Chuanjie

2014-08-01

100

Structural Glazing Solutions for Protective Glazing  

Microsoft Academic Search

Tragic world events have opened our eyes to the vulnerability and false sense of security in today's buildings around the globe. The horrific loss of life and property from terrorist attacks on these structures has forced building owners, investors, government authorities, building occupants and insurance companies to seek new solutions to protect people from these events as well as from

Axel H. Giesecke; Kenneth Yarosh; Dow Corning

101

Supersaturated zincate solutions: A structural study  

SciTech Connect

The anodic oxidation of zinc electrodes in concentrated potassium hydroxide solutions that occurs during the discharge of alkaline zinc batteries leads to electrolytes with a Zn(II) content much higher than that obtained when a solid ZnO is equilibrated with KOH solutions of the same concentration at the same temperature. The Zn(II) excess slowly precipitates as ZnO from these supersaturated solutions, disturbing the working of the batteries. Undersaturated and supersaturated zincate solutions have been prepared electrochemically and chemically, and studied using nuclear magnetic resonance (NMR) spectrometry and extended X-ray absorption fine structure (EXAFS). {sup 67}Zn NMR spectroscopy shows only one resonance line, the area of which first increases with the Zn concentration until saturation and then remains constant for higher concentrations. EXAFS shows four oxygen neighbors at a distance of 1.979 {angstrom} of each zinc atom. Identical results were obtained with undersaturated and saturated zincate solutions. No Zn...Zn correlation was found indicating there is no polymeric species in the supersaturated solutions. It is proposed that in zincate solution (KOH 8M) the supersaturation is due to the presence of oxodihydroxozincate (ZnO(OH){sub 2}{sup 2{minus}}).

Debiemme-Chouvy, C.; Vedel, J. [Ecole Nationale Superieure de Chimie de Paris (France). Lab. d`Electrochimie; Bellissent-Funel, M. [CEN Saclay, Gif-sur-Yvette (France). Lab. Leon Brillouin; Cortes, R. [Univ. d`Orsay (France)

1995-05-01

102

MACROMOLECULAR PHYSIOLOGY OF PLASTIDS  

PubMed Central

Sequential changes occurring in the etioplasts of the primary leaf of 7-day-old dark-grown barley seedlings upon continuous illumination with 20 lux have been investigated by electron microscopy, in vivo spectrophotometry, and thin-layer chromatography. Following photoconversion of the protochlorophyllide pigment to chlorophyllide and the structural transformation of the crystalline prolamellar bodies, the tubules of the prolamellar bodies are dispersed into the primary lamellar layers. As both chlorophyll a and b accumulate, extensive formation of grana takes place. After 4 hr of greening, protochlorophyllide starts to reaccumulate, and concomitantly both large and small crystalline prolamellar bodies are formed. This protochlorophyllide is rapidly photoconverted upon exposure of the leaves to high light intensity, which also effects a rapid reorganization of the recrystallized prolamellar bodies into primary lamellar layers. PMID:5411076

Henningsen, K. W.; Boynton, J. E.

1970-01-01

103

Combined Effects of Agitation, Macromolecular Crowding, and Interfaces on Amyloidogenesis*  

PubMed Central

Amyloid formation and accumulation is a hallmark of protein misfolding diseases and is associated with diverse pathologies including type II diabetes and Alzheimer's disease (AD). In vitro, amyloidogenesis is widely studied in conditions that do not simulate the crowded and viscous in vivo environment. A high volume fraction of most biological fluids is occupied by various macromolecules, a phenomenon known as macromolecular crowding. For some amyloid systems (e.g. ?-synuclein) and under shaking condition, the excluded volume effect of macromolecular crowding favors aggregation, whereas increased viscosity reduces the kinetics of these reactions. Amyloidogenesis can also be catalyzed by hydrophobic-hydrophilic interfaces, represented by the air-water interface in vitro and diverse heterogeneous interfaces in vivo (e.g. membranes). In this study, we investigated the effects of two different crowding polymers (dextran and Ficoll) and two different experimental conditions (with and without shaking) on the fibrilization of amyloid-? peptide, a major player in AD pathogenesis. Specifically, we demonstrate that, during macromolecular crowding, viscosity dominates over the excluded volume effect only when the system is spatially non homogeneous (i.e. an air-water interface is present). We also show that the surfactant activity of the crowding agents can critically influence the outcome of macromolecular crowding and that the structure of the amyloid species formed may depend on the polymer used. This suggests that, in vivo, the outcome of amyloidogenesis may be affected by both macromolecular crowding and spatial heterogeneity (e.g. membrane turn-over). More generally, our work suggests that any factors causing changes in crowding may be susceptibility factors in AD. PMID:22988239

Lee, Chiu Fan; Bird, Sarah; Shaw, Michael; Jean, Létitia; Vaux, David J.

2012-01-01

104

Macromolecular solvation energies derived from small molecule crystal morphology.  

PubMed Central

The morphology of small molecule crystals provides a model for evaluating surface solvation energies in a system with similar packing density to that observed for amino acid residues in proteins. The solvation energies associated with the transfer of methylene and carboxyl groups between vacuum and aqueous phases are estimated to be approx. $40 and -260 cal/A2, respectively, from an analysis of the morphology of succinic acid crystals. These solvation energies predict values for contact angles in reasonable agreement with measurements determined from macroscopic monolayer surfaces. Transfer free energies between vapor and water phases for a series of carboxylic acids are also predicted reasonably well by these solvation energies, provided the surface exposure of different groups is quantitated with the molecular surface area rather than the more traditional accessible surface area. In general, molecular surfaces and molecular surface areas are seen to have important advantages for characterizing the structure and energetics of macromolecular surfaces. Crystal faces of succinic acid with the lowest surface energies in aqueous solution are characteristically smooth. Increasing surface roughness and apolarity are associated with higher surface energies, which suggests an approach for modifying the surface properties of proteins and other macromolecules. PMID:8268799

Rees, D. C.; Wolfe, G. M.

1993-01-01

105

Structures in aqueous solutions of nonionic tensides  

Microsoft Academic Search

Since Bordier succeeded in isolating solutions of hydrophobic proteins with the aid of aqueous Triton X-114 (reaction product\\u000a of p-octylphenol with 7–8 mol ethylene oxide), more and more biochemists and biotechnologists have become interested in such\\u000a systems. We have been able to demonstrate that lamellar structures formed in miscibility gaps of polyglycol ether\\/water systems\\u000a are responsbile for this isolation. We

R. Heusch; F. Kopp

106

Temperature-dependent macromolecular X-ray crystallography  

PubMed Central

X-ray crystallography provides structural details of biological macromolecules. Whereas routine data are collected close to 100?K in order to mitigate radiation damage, more exotic temperature-controlled experiments in a broader temperature range from 15?K to room temperature can provide both dynamical and structural insights. Here, the dynamical behaviour of crystalline macromolecules and their surrounding solvent as a function of cryo-temperature is reviewed. Experimental strategies of kinetic crystallography are discussed that have allowed the generation and trapping of macromolecular intermediate states by combining reaction initiation in the crystalline state with appropriate temperature profiles. A particular focus is on recruiting X-ray-induced changes for reaction initiation, thus unveiling useful aspects of radiation damage, which otherwise has to be minimized in macromolecular crystallography. PMID:20382997

Weik, Martin; Colletier, Jacques-Philippe

2010-01-01

107

Solution Structures of PPAR?2/RXR? Complexes.  

PubMed

PPAR? is a key regulator of glucose homeostasis and insulin sensitization. PPAR? must heterodimerize with its dimeric partner, the retinoid X receptor (RXR), to bind DNA and associated coactivators such as p160 family members or PGC-1? to regulate gene networks. To understand how coactivators are recognized by the functional heterodimer PPAR?/RXR? and to determine the topological organization of the complexes, we performed a structural study using small angle X-ray scattering of PPAR?/RXR? in complex with DNA from regulated gene and the TIF2 receptor interacting domain (RID). The solution structures reveal an asymmetry of the overall structure due to the crucial role of the DNA in positioning the heterodimer and indicate asymmetrical binding of TIF2 to the heterodimer. PMID:23319938

Osz, Judit; Pethoukhov, Maxim V; Sirigu, Serena; Svergun, Dmitri I; Moras, Dino; Rochel, Natacha

2012-01-01

108

Solution Structures of PPAR?2/RXR? Complexes  

PubMed Central

PPAR? is a key regulator of glucose homeostasis and insulin sensitization. PPAR? must heterodimerize with its dimeric partner, the retinoid X receptor (RXR), to bind DNA and associated coactivators such as p160 family members or PGC-1? to regulate gene networks. To understand how coactivators are recognized by the functional heterodimer PPAR?/RXR? and to determine the topological organization of the complexes, we performed a structural study using small angle X-ray scattering of PPAR?/RXR? in complex with DNA from regulated gene and the TIF2 receptor interacting domain (RID). The solution structures reveal an asymmetry of the overall structure due to the crucial role of the DNA in positioning the heterodimer and indicate asymmetrical binding of TIF2 to the heterodimer. PMID:23319938

Osz, Judit; Pethoukhov, Maxim V.; Sirigu, Serena; Svergun, Dmitri I.; Moras, Dino; Rochel, Natacha

2012-01-01

109

Macromolecular Crystal Growth by Means of Microfluidics  

NASA Technical Reports Server (NTRS)

We have performed a feasibility study in which we show that chip-based, microfluidic (LabChip(TM)) technology is suitable for protein crystal growth. This technology allows for accurate and reliable dispensing and mixing of very small volumes while minimizing bubble formation in the crystallization mixture. The amount of (protein) solution remaining after completion of an experiment is minimal, which makes this technique efficient and attractive for use with proteins, which are difficult or expensive to obtain. The nature of LabChip(TM) technology renders it highly amenable to automation. Protein crystals obtained in our initial feasibility studies were of excellent quality as determined by X-ray diffraction. Subsequent to the feasibility study, we designed and produced the first LabChip(TM) device specifically for protein crystallization in batch mode. It can reliably dispense and mix from a range of solution constituents into two independent growth wells. We are currently testing this design to prove its efficacy for protein crystallization optimization experiments. In the near future we will expand our design to incorporate up to 10 growth wells per LabChip(TM) device. Upon completion, additional crystallization techniques such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility for the International Space Station as well as on the ground.

vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

2002-01-01

110

Solvent-assisted NMR imaging or heterogeneous coal macromolecular networks  

SciTech Connect

Solvent swelling has been employed to probe the physical structure of coal (1). The swelling behavior of bituminous coals in various solvents has been used to assess different strengths or types of secondary interactions which determine their macromolecular structures (2-5). The phenomenon of solvent transport into coal during solvent swelling has also been extensively investigated by numerous researchers (6-10). Recently, we have obtained important information concerning solvent accessibility in coals and maceral domains by proton NMR imaging of mobile proton distributions resulting from solvent swelling (11). Images of coals swollen with perdeuterated solvents were used to map mobile phases in the coal macromolecular structure, while images obtained with protic solvents mapped distributions of the ingressed solvent. For the present purposes 2-D images are sufficient and their acquisition is suitably fast. In order to ensure that the transport process was also two-dimensional, the upper and lower sample surfaces were protected from solvent infiltration by glass coverslips which restricted the flow of solvent to cross only the exposed faces of the sample. Each sample is rectangular with initial dimensions on the order of 2 {times} 2 {times} 1 mm. The experimental protocol involved immersing the sample in the solvent for a period of time, removing it from the solvent bath, acquiring an image, and re-immersing it. Figure 1 presents transient images together with one-dimensional projections for each of the three macromolecular systems.

French, D.C.; Cody, G.D.; Botto, R.E.

1993-09-01

111

Structures of TraI in Solution  

PubMed Central

Bacterial conjugation, a DNA transfer mechanism involving transport of one plasmid strand from donor to recipient, is driven by plasmid-encoded proteins. The F TraI protein nicks one F plasmid strand, separates cut and uncut strands, and pilots the cut strand through a secretion pore into the recipient. TraI is a modular protein with identifiable nickase, ssDNA-binding, helicase and protein-protein interaction domains. While domain structures corresponding to roughly 1/3 of TraI have been determined, there has been no comprehensive structural study of the entire TraI molecule, nor an examination of structural changes to TraI upon binding DNA. Here, we combine solution studies using small-angle scattering and circular dichroism spectroscopy with molecular Monte Carlo and molecular dynamics simulations to assess solution behavior of individual and groups of domains. Despite having several long (>100 residues) apparently disordered or highly dynamic regions, TraI folds into a compact molecule. Based on the biophysical characterization, we have generated models of intact TraI. These data and the resulting models have provided clues to the regulation of TraI function. PMID:24898939

Clark, Nicholas J.; Raththagala, Madushi; Wright, Nathan T.; Buenger, Elizabeth A.; Schildbach, Joel F.; Krueger, Susan; Curtis, Joseph E.

2014-01-01

112

Quantum chemistry of macromolecular shape  

NASA Astrophysics Data System (ADS)

Some of the new developments in the quantum-chemical study of macromolecular shapes are reviewed, with special emphasis on the additive fuzzy electron density fragmentation methods and on the algebraic-topological shape group analysis of global and local shape features of fuzzy three-dimensional bodies of electron densities of macromolecules. Earlier applications of these methods to actual macromolecules are reviewed, including studies on the anticancer drug taxol, the proteins bovine insulin and HIV protease, and other macromolecules. The results of test calculations establishing the accuracy of these methods are also reviewed. The spherically weighted affine transformation technique is described and proposed for the deformation of electron densities approximating the changes occurring in small conformational displacements of atomic nuclei in macromolecules.

Mezey, Paul G.

113

Biophysical Highlights from 54 Years of Macromolecular Crystallography  

PubMed Central

The United Nations has declared 2014 the International Year of Crystallography, and in commemoration, this review features a selection of 54 notable macromolecular crystal structures that have illuminated the field of biophysics in the 54 years since the first excitement of the myoglobin and hemoglobin structures in 1960. Chronological by publication of the earliest solved structure, each illustrated entry briefly describes key concepts or methods new at the time and key later work leveraged by knowledge of the three-dimensional atomic structure. PMID:24507592

Richardson, Jane S.; Richardson, David C.

2014-01-01

114

Structure-thermodynamics relation of electrolyte solutions  

NASA Astrophysics Data System (ADS)

The structure of aqueous LiCl, NaCl, KCl, CsCl, KF, and NaI solutions is calculated by molecular dynamics (MD) simulations of the frequently employed Dang force-field in SPC/E water. By using liquid state theory, we integrate the structure to obtain the electrolytes' osmotic coefficient ? and systematically investigate force-field quality and structural consequences to ion-specific bulk thermodynamics. The osmotic coefficients ?? calculated from the exact compressibility route for the cation-Cl- force-fields match experiments for concentrations ? ?2M, while NaI and KF parameters fail. Comparison of ?? with ?v from the virial route, which relies on the pair potential approximation, shows that many-body effects become important for all salts above ? ?0.5M. They can be efficiently corrected, however, by employing a salt-type and ?-dependent dielectric constant ?(? ), generalizing previous observations on NaCl only. For physiological concentrations, ? ?0.5M, the specific osmotic behavior is found to be determined by the short-ranged cation-anion pair potential only and is strongly related to the second virial coefficient of the latter. Presented methods and findings, based on simple integrations over the electrolyte structure, enable efficient MD force-field refinement by direct benchmarking to the sensitive electrolyte thermodynamics, instead to noncollective, single ion properties.

Kalcher, Immanuel; Dzubiella, Joachim

2009-04-01

115

Macromolecular synthesis by yeasts under frozen conditions  

E-print Network

by the protein synthesis inhibitor cycloheximide. Experi- ments at -5°C under frozen and liquid conditionsMacromolecular synthesis by yeasts under frozen conditions Pierre Amato,* Shawn Doyle and Brent C

Christner, Brent C.

116

Polybivalency and disordered proteins in ordering macromolecular assemblies.  

PubMed

Intrinsically disordered proteins (IDPs) are prevalent in macromolecular assemblies and are thought to mediate protein recognition in complex regulatory processes and signaling pathways. The formation of a polybivalent scaffold is a key process by which IDPs drive early steps in macromolecular assemblies. Three intrinsically disordered proteins, IC, Swallow and Nup159, are core components, respectively, of cytoplasmic dynein, bicoid mRNA localization apparatus, and nuclear pore complexes. In all three systems, the hub protein LC8 recognizes on the IDP, short linear motifs that are fully disordered in the apo form, but adopt a ?-strand when bound to LC8. The IDP/LC8 complex forms a bivalent scaffold primed to bind additional bivalent ligands. Scaffold formation also promotes self-association and/or higher order organization of the IDP components at a site distant from LC8 binding. Rigorous thermodynamic analyses imply that association of additional bivalent ligands is driven by entropic effects where the first binding event is weak but subsequent binding of additional ligands occurs with higher affinity. Here, we review specific examples of macromolecular assemblies in which polybivalency of aligned IDP duplexes not only enhances binding affinity and results in formation of a stable complex but also compensates unfavorable steric and enthalpic interactions. We propose that polybivalent scaffold assembly involving IDPs and LC8-like proteins is a general process in the cell biology of a class of multi-protein structures that are stable yet fine-tuned for diverse cellular requirements. PMID:25263009

Barbar, Elisar; Nyarko, Afua

2014-09-27

117

Macromolecular crowding conditions enhance glycation and oxidation of whey proteins in ultrasound-induced Maillard reaction.  

PubMed

High intensity ultrasound (HIUS) can promote Maillard reaction (MR). Macromolecular crowding conditions accelerate reactions and stabilise protein structure. The aim of this study was to investigate if combined application of ultrasound and macromolecular crowding can improve efficiency of MR. The presence of crowding agent (polyethylene glycol) significantly increased ultrasound-induced whey protein (WP) glycation by arabinose. An increase in glycation efficiency results only in slight change of WP structure. Macromolecular crowding intensifies oxidative modifications of WP, as well as formation of amyloid-like structures by enhancement of MR. Solubility at different pH, thermal stability and antioxidative capacity of glycated WP were increased, especially in the presence of crowding agent, compared to sonicated nonglycated proteins. The application of HIUS under crowding conditions can be a new approach for enhancement of reactions in general, enabling short processing time and mild conditions, while preserving protein structure and minimising protein aggregation. PMID:25660883

Perusko, Marija; Al-Hanish, Ayah; Cirkovic Velickovic, Tanja; Stanic-Vucinic, Dragana

2015-06-15

118

Organoactinide chemistry: synthesis, structure, and solution dynamics  

SciTech Connect

This thesis considers three aspects of organoactinide chemistry. In chapter one, a bidentate phosphine ligand was used to kinetically stabilize complexes of the type Cp/sub 2/MX/sub 2/. Ligand redistribution processes are present throughout the synthetic work, as has often been observed in uranium cyclopentadienyl chemistry. The effects of covalent M-L bonding on the solution and solid state properties of U(III) coordination complexes are considered. In particular, the nature of the more subtle interaction between the metal and the neutral ligand are examined. Using relative basicity data obtained in solution, and solid state structural data (and supplemented by gas phase photoelectron measurements), it is demonstrated that the more electron rich U(III) centers engage in significant U ..-->.. L ..pi..-donation. Trivalent uranium is shown to be capable of acting either as a one- or two-electron reducing agent toward a wide variety of unsaturated organic and inorganic molecules, generating molecular classes unobtainable via traditional synthetic approaches, as well as offering an alternative synthetic approach to molecules accessible via metathesis reactions. Ligand redistribution processes are again observed, but given the information concerning ligand lability, this reactivity pattern is applied to the synthesis of pure materials inaccessible from redox chemistry. 214 refs., 33 figs., 10 tabs.

Brennan, J.G.

1985-12-01

119

Cryosalts: suppression of ice formation in macromolecular crystallography.  

PubMed

Quality data collection for macromolecular cryocrystallography requires suppressing the formation of crystalline or microcrystalline ice that may result from flash-freezing crystals. Described here is the use of lithium formate, lithium chloride and other highly soluble salts for forming ice-ring-free aqueous glasses upon cooling from ambient temperature to 100 K. These cryosalts are a new class of cryoprotectants that are shown to be effective with a variety of commonly used crystallization solutions and with proteins crystallized under different conditions. The influence of cryosalts on crystal mosaicity and diffraction resolution is comparable with or superior to traditional organic cryoprotectants. PMID:10944336

Rubinson, K A; Ladner, J E; Tordova, M; Gilliland, G L

2000-08-01

120

Molecular docking simulations for macromolecularly imprinted polymers  

PubMed Central

Molecularly imprinted polymers are fully synthetic antibody mimics prepared via the crosslinking of organic monomers in the presence of an analyte. This general procedure is now well developed for small molecule templates; however, attempts to extend the same techniques to the macromolecular regime have achieved limited success to date. We employ molecular docking simulations to investigate the interactions between albumin, a common protein template, and frequently employed ligands used in the literature at the molecular level. Specifically, we determine the most favorable binding sites for these ligands on albumin and determine the types of non-covalent interactions taking place based on the amino acids present nearby this binding pocket. Our results show that hydrogen bonding, electrostatic interactions, and hydrophobic interactions occur between amino acids side chains and ligands. Several interactions are also taking place with the polypeptide backbone, potentially disrupting the protein’s secondary structure. We show that several of the ligands preferentially bind to the same sites on the protein, which indicates that if multiple monomers are used during synthesis then competition for the same amino acids could lead to non-specific recognition. Both of these results provide rational explanations for the lack of success to date in the field. PMID:22287827

Kryscio, David R.; Shi, Yue; Ren, Pengyu; Peppas, Nicholas A.

2011-01-01

121

Flexibility damps macromolecular crowding effects on protein folding dynamics: Application to the murine prion protein (121-231)  

NASA Astrophysics Data System (ADS)

A model of protein folding kinetics is applied to study the combined effects of protein flexibility and macromolecular crowding on protein folding rate and stability. It is found that the increase in stability and folding rate promoted by macromolecular crowding is damped for proteins with highly flexible native structures. The model is applied to the folding dynamics of the murine prion protein (121-231). It is found that the high flexibility of the native isoform of the murine prion protein (121-231) reduces the effects of macromolecular crowding on its folding dynamics. The relevance of these findings for the pathogenic mechanism are discussed.

Bergasa-Caceres, Fernando; Rabitz, Herschel A.

2014-01-01

122

Molecular simulations of concentrated aqueous solutions: ionic equilibrium structures in solutions  

NASA Astrophysics Data System (ADS)

The computer simulation methods have been applied to study the structure of aqueous solutions of simple ionic salts in the region of very high concentrations. The calculations of ionic structures in solutions were performed for NaOH, NaCl, LiCl and MgCl2 solutions. The concentrations ranged from 0.2M to saturated solutions, in some case as much as 19M.

Bartczak, Witold M.; Zapalowski, Michal; Wolf, Krystyna

2001-08-01

123

Atomic Structure Schrdinger equation has approximate solutions for multi-  

E-print Network

Atomic Structure Schrödinger equation has approximate solutions for multi- electron atoms, which indicate that all atoms are like hydrogen Atomic Structure Schrödinger equation has approximate solutions 3s 3p 3d Energy hydrogen multi-electron #12;Atomic Structure · orbitals are populated by electrons

Zakarian, Armen

124

Macromolecular HPMA-based nanoparticles with cholesterol for solid-tumor targeting: detailed study of the inner structure of a highly efficient drug delivery system.  

PubMed

We report a rigorous investigation into the detailed structure of nanoparticles already shown to be successful drug delivery nanocarriers. The basic structure of the drug conjugates consists of an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer bearing the anticancer drug doxorubicin (Dox) bound via a pH-sensitive hydrazone bond and a defined amount of cholesterol moieties that vary in hydrophobicity. The results show that size, anisotropy, and aggregation number N(aggr) of the nanoparticles grows with increasing cholesterol content. From ab initio calculations, we conclude that the most probable structure of HPMA copolymer-cholesterol nanoparticles is a pearl necklace structure, where ellipsoidal pearls mainly composed of cholesterol are covered by a HPMA shell; pearls are connected by bridges composed of hydrophilic HPMA copolymer chains. Using a combination of techniques, we unambiguously show that the Dox moieties are not impregnated inside a cholesterol core but are instead uniformly distributed across the whole nanoparticle, including the hydrophilic HPMA shell surface. PMID:22793269

Filippov, Sergey K; Chytil, Petr; Konarev, Petr V; Dyakonova, Margarita; Papadakis, Christinem; Zhigunov, Alexander; Plestil, Josef; Stepanek, Petr; Etrych, Tomas; Ulbrich, Karel; Svergun, Dmitri I

2012-08-13

125

An autonomous structural health monitoring solution  

NASA Astrophysics Data System (ADS)

Combining advanced sensor technologies, with optimised data acquisition and diagnostic and prognostic capability, structural health monitoring (SHM) systems provide real-time assessment of the integrity of bridges, buildings, aircraft, wind turbines, oil pipelines and ships, leading to improved safety and reliability and reduced inspection and maintenance costs. The implementation of power harvesting, using energy scavenged from ambient sources such as thermal gradients and sources of vibration in conjunction with wireless transmission enables truly autonomous systems, reducing the need for batteries and associated maintenance in often inaccessible locations, alongside bulky and expensive wiring looms. The design and implementation of such a system however presents numerous challenges. A suitable energy source or multiple sources capable of meeting the power requirements of the system, over the entire monitoring period, in a location close to the sensor must be identified. Efficient power management techniques must be used to condition the power and deliver it, as required, to enable appropriate measurements to be taken. Energy storage may be necessary, to match a continuously changing supply and demand for a range of different monitoring states including sleep, record and transmit. An appropriate monitoring technique, capable of detecting, locating and characterising damage and delivering reliable information, whilst minimising power consumption, must be selected. Finally a wireless protocol capable of transmitting the levels of information generated at the rate needed in the required operating environment must be chosen. This paper considers solutions to some of these challenges, and in particular examines SHM in the context of the aircraft environment.

Featherston, Carol A.; Holford, Karen M.; Pullin, Rhys; Lees, Jonathan; Eaton, Mark; Pearson, Matthew

2013-05-01

126

Multi-crystal anomalous diffraction for low-resolution macromolecular phasing.  

PubMed

Multiwavelength anomalous diffraction (MAD) and single-wavelength anomalous diffraction (SAD) are the two most commonly used methods for de novo determination of macromolecular structures. Both methods rely on the accurate extraction of anomalous signals; however, because of factors such as poor intrinsic order, radiation damage, inadequate anomalous scatterers, poor diffraction quality and other noise-causing factors, the anomalous signal from a single crystal is not always good enough for structure solution. In this study, procedures for extracting more accurate anomalous signals by merging data from multiple crystals are devised and tested. SAD phasing tests were made with a relatively large (1456 ordered residues) poorly diffracting (d(min) = 3.5?Å) selenomethionyl protein (20 Se). It is quantified that the anomalous signal, success in substructure determination and accuracy of phases and electron-density maps all improve with an increase in the number of crystals used in merging. Structure solutions are possible when no single crystal can support structural analysis. It is proposed that such multi-crystal strategies may be broadly useful when only weak anomalous signals are available. PMID:21206061

Liu, Qun; Zhang, Zhen; Hendrickson, Wayne A

2011-01-01

127

Multi-crystal anomalous diffraction for low-resolution macromolecular phasing  

PubMed Central

Multiwavelength anomalous diffraction (MAD) and single-wavelength anomalous diffraction (SAD) are the two most commonly used methods for de novo determination of macromolecular structures. Both methods rely on the accurate extraction of anomalous signals; however, because of factors such as poor intrinsic order, radiation damage, inadequate anomalous scatterers, poor diffraction quality and other noise-causing factors, the anomalous signal from a single crystal is not always good enough for structure solution. In this study, procedures for extracting more accurate anomalous signals by merging data from multiple crystals are devised and tested. SAD phasing tests were made with a relatively large (1456 ordered residues) poorly diffracting (d min = 3.5?Å) selenomethionyl protein (20 Se). It is quantified that the anomalous signal, success in substructure determination and accuracy of phases and electron-density maps all improve with an increase in the number of crystals used in merging. Structure solutions are possible when no single crystal can support structural analysis. It is proposed that such multi-crystal strategies may be broadly useful when only weak anomalous signals are available. PMID:21206061

Liu, Qun; Zhang, Zhen; Hendrickson, Wayne A.

2011-01-01

128

Low-resolution structures of proteins in solution retrieved from X-ray scattering with a genetic algorithm.  

PubMed

Small-angle x-ray solution scattering (SAXS) is analyzed with a new method to retrieve convergent model structures that fit the scattering profiles. An arbitrary hexagonal packing of several hundred beads containing the problem object is defined. Instead of attempting to compute the Debye formula for all of the possible mass distributions, a genetic algorithm is employed that efficiently searches the configurational space and evolves best-fit bead models. Models from different runs of the algorithm have similar or identical structures. The modeling resolution is increased by reducing the bead radius together with the search space in successive cycles of refinement. The method has been tested with protein SAXS (0.001 < S < 0.06 A(-1)) calculated from x-ray crystal structures, adding noise to the profiles. The models obtained closely approach the volumes and radii of gyration of the known structures, and faithfully reproduce the dimensions and shape of each of them. This includes finding the active site cavity of lysozyme, the bilobed structure of gamma-crystallin, two domains connected by a stalk in betab2-crystallin, and the horseshoe shape of pancreatic ribonuclease inhibitor. The low-resolution solution structure of lysozyme has been directly modeled from its experimental SAXS profile (0.003 < S < 0.03 A(-1)). The model describes lysozyme size and shape to the resolution of the measurement. The method may be applied to other proteins, to the analysis of domain movements, to the comparison of solution and crystal structures, as well as to large macromolecular assemblies. PMID:9635731

Chacón, P; Morán, F; Díaz, J F; Pantos, E; Andreu, J M

1998-06-01

129

Effects of Macromolecular Crowding on Genetic Networks  

PubMed Central

The intracellular environment is crowded with proteins, DNA, and other macromolecules. Under physiological conditions, macromolecular crowding can alter both molecular diffusion and the equilibria of bimolecular reactions and therefore is likely to have a significant effect on the function of biochemical networks. We propose a simple way to model the effects of macromolecular crowding on biochemical networks via an appropriate scaling of bimolecular association and dissociation rates. We use this approach, in combination with kinetic Monte Carlo simulations, to analyze the effects of crowding on a constitutively expressed gene, a repressed gene, and a model for the bacteriophage ? genetic switch, in the presence and absence of nonspecific binding of transcription factors to genomic DNA. Our results show that the effects of crowding are mainly caused by the shift of association-dissociation equilibria rather than the slowing down of protein diffusion, and that macromolecular crowding can have relevant and counterintuitive effects on biochemical network performance. PMID:22208186

Morelli, Marco J.; Allen, Rosalind J.; Rein ten Wolde, Pieter

2011-01-01

130

A Sco protein among the hypothetical proteins of Bacillus lehensis G1: Its 3D macromolecular structure and association with Cytochrome C Oxidase  

PubMed Central

Background At least a quarter of any complete genome encodes for hypothetical proteins (HPs) which are largely non-similar to other known, well-characterized proteins. Predicting and solving their structures and functions is imperative to aid understanding of any given organism as a complete biological system. The present study highlights the primary effort to classify and cluster 1202 HPs of Bacillus lehensis G1 alkaliphile to serve as a platform to mine and select specific HP(s) to be studied further in greater detail. Results All HPs of B. lehensis G1 were grouped according to their predicted functions based on the presence of functional domains in their sequences. From the metal-binding group of HPs of the cluster, an HP termed Bleg1_2507 was discovered to contain a thioredoxin (Trx) domain and highly-conserved metal-binding ligands represented by Cys69, Cys73 and His159, similar to all prokaryotic and eukaryotic Sco proteins. The built 3D structure of Bleg1_2507 showed that it shared the ?????? core structure of Trx-like proteins as well as three flanking ?-sheets, a 310 –helix at the N-terminus and a hairpin structure unique to Sco proteins. Docking simulations provided an interesting view of Bleg1_2507 in association with its putative cytochrome c oxidase subunit II (COXII) redox partner, Bleg1_2337, where the latter can be seen to hold its partner in an embrace, facilitated by hydrophobic and ionic interactions between the proteins. Although Bleg1_2507 shares relatively low sequence identity (47%) to BsSco, interestingly, the predicted metal-binding residues of Bleg1_2507 i.e. Cys-69, Cys-73 and His-159 were located at flexible active loops similar to other Sco proteins across biological taxa. This highlights structural conservation of Sco despite their various functions in prokaryotes and eukaryotes. Conclusions We propose that HP Bleg1_2507 is a Sco protein which is able to interact with COXII, its redox partner and therefore, may possess metallochaperone and redox functions similar to other documented bacterial Sco proteins. It is hoped that this scientific effort will help to spur the search for other physiologically relevant proteins among the so-called “orphan” proteins of any given organism. PMID:24641837

2014-01-01

131

Small angle neutron scattering studies of coal-extract solutions  

SciTech Connect

Interest in the physics and chemistry of coal extracts has extended for over 100 years. Early on it was recognized that pyridine was a particularly good solvent capable of extracting a significant weight percent of intermediate rank coals. Many of the current theories regarding the macromolecular structure of coals (type III kerogens) are based on the fact that there exists a physically definable limit in the extractability of soluble organics from coal in pyridine. The non-extractable residue is generally considered to be a cross-linked macromolecular network. The extract-solvent {open_quotes}solutions{close_quotes}, although acknowledged to be far from ideal (thermodynamically), are presumed to be {open_quotes}molecular solutions{close_quotes} in the sense that random mixing of the constituents occurs within a single solution phase. This research set out to characterize the solution structures of coal extracts to gain insight into the nature of coal-solvent interactions.

Thiyagarajan, P. [Argonne National Laboratory, IL (United States); Cody, G.D. [Carnegie Institution of Washington, DC (United States). Geophysical Laboratory

1997-08-01

132

Viral capsomere structure, surface processes and growth kinetics in the crystallization of macromolecular crystals visualized by in situ atomic force microscopy  

NASA Astrophysics Data System (ADS)

In situ atomic force microscopy (AFM) was used to investigate surface evolution during the growth of single crystals of turnip yellow mosaic virus (TYMV), cucumber mosaic virus (CMV) and glucose isomerase. Growth of these crystals proceeded by two-dimensional (2D) nucleation. For glucose isomerase, from supersaturation dependencies of tangential step rates and critical step length, the kinetic coefficients of the steps and the surface free energy of the step edge were calculated for different crystallographic directions. The molecular structure of the step edges, the adsorption of individual virus particles and their aggregates, and the initial stages of formation of 2D nuclei on the surfaces of TYMV and CMV crystals were recorded. The surfaces of individual TYMV virions within crystals were visualized, and hexameric and pentameric capsomers of the T=3 capsids were clearly resolved. This, so far as we are aware, is the first direct visualization of the capsomere structure of a virus by AFM. In the course of recording the in situ development of the TYMV crystals, a profound restructuring of the surface arrangement was observed. This transformation was highly cooperative in nature, but the transitions were unambiguous and readily explicable in terms of an organized loss of classes of virus particles from specific lattice positions.

Malkin, A. J.; Kuznetsov, Yu. G.; McPherson, A.

2001-11-01

133

Thermodynamic signatures in macromolecular interactions involving conformational flexibility.  

PubMed

The energetics of macromolecular interactions are complex, particularly where protein flexibility is involved. Exploiting serendipitous differences in the plasticity of a series of closely related trypsin variants, we analyzed the enthalpic and entropic contributions accompanying interaction with L45K-eglin C. Binding of the four variants show significant differences in released heat, although the affinities vary little, in accordance with the principle of enthalpy-entropy compensation. Binding of the most disordered variant is almost entirely enthalpically driven, with practically no entropy change. As structures of the complexes reveal negligible differences in protein-inhibitor contacts, we conclude that solvent effects contribute significantly to binding affinities. PMID:25003391

Menzel, Anja; Neumann, Piotr; Schwieger, Christian; Stubbs, Milton T

2014-07-01

134

Development of highly chemoselective bulky zincate complex, tBu4ZnLi2: design, structure, and practical applications in small-/macromolecular synthesis.  

PubMed

We present full details of the unique reactivities of the newly developed dianion-type bulky zincate, dilithium tetra-tert-butylzincate (tBu(4)ZnLi(2)). With this reagent, halogen-zinc exchange reaction of variously functionalized haloaromatics and anionic polymerization of N-isopropylacrylamide (NIPAm)/styrene with excellent chemoselectivity were realized. Halogen-zinc exchange reaction followed by electrophilic trapping with propargyl bromide provided a convenient route to functionalized phenylallenes, particularly those with electrophilic functional groups (such as cyano, amide and halogens). Spectral and computational studies of the structure in the gas and liquid phases indicated extraordinary stabilization of this dianion-type zincate by its bulky ligands. PMID:18816554

Furuyama, Taniyuki; Yonehara, Mitsuhiro; Arimoto, Sho; Kobayashi, Minoru; Matsumoto, Yotaro; Uchiyama, Masanobu

2008-01-01

135

The prestressability problem of tensegrity structures: some analytical solutions  

E-print Network

The prestressability problem of tensegrity structures: some analytical solutions Cornel Sultan a formulate the general prestressability conditions for tensegrity structures. These conditions are expressed as a set of nonlinear equations and inequalities on the tendon tensions. Several examples of tensegrity

Sultan, Cornel

136

Two-dimensional macromolecular distributions reveal detailed architectural features in high-amylose starches.  

PubMed

Two-dimensional (2D) structural distributions based on macromolecular size and branch chain-length are obtained for three maize starches with different amylose contents (one normal and two high-amylose varieties). Data were obtained using an analytical methodology combining chemical fractionation, enzymatic debranching, and offline 2D size-exclusion chromatography with multiple detection. The 2D distributions reveal novel features in the branching structure of high-amylose maize starches. Normal maize starch shows well-resolved structural topologies, corresponding to the amylopectin and amylose macromolecular populations. However, high-amylose maize starches exhibit very complex topologies with significant features between those of amylose and amylopectin, showing the presence of distinct intermediate components. These have the macromolecular size of amylose but similar branching structure to amylopectin, except for a higher proportion of longer branches. These structural features of the intermediate components can be related to a less tightly controlled biosynthesis of the branching structures in high-amylose maize starch mutants, which may prevent these molecules from maturing into full-size amylopectin. This altered macromolecular branched architecture of high-amylose starches probably contribute to their better nutritional properties. PMID:25256517

Vilaplana, Francisco; Meng, Di; Hasjim, Jovin; Gilbert, Robert G

2014-11-26

137

HIGH PRESSURE CRYOCOOLING FOR MACROMOLECULAR CRYSTALLOGRAPHY  

E-print Network

high-pressure cryocooled and excellent crystal diffraction has been obtained without adding any. After achieving his B.S. degree in 1999, he spent 26 months in Korean Army as a medic. Then he enteredHIGH PRESSURE CRYOCOOLING FOR MACROMOLECULAR CRYSTALLOGRAPHY A Dissertation Presented

Gruner, Sol M.

138

Probing the hydration water diffusion of macromolecular surfaces and interfaces  

NASA Astrophysics Data System (ADS)

We probe the translational dynamics of the hydration water surrounding the macromolecular surfaces of selected polyelectrolytes, lipid vesicles and intrinsically disordered proteins with site specificity in aqueous solutions. These measurements are made possible by the recent development of a new instrumental and methodological approach based on Overhauser dynamic nuclear polarization (DNP)-enhanced nuclear magnetic resonance (NMR) spectroscopy. This technique selectively amplifies 1H NMR signals of hydration water around a spin label that is attached to a molecular site of interest. The selective 1H NMR amplification within molecular length scales of a spin label is achieved by utilizing short-distance range (~r-3) magnetic dipolar interactions between the 1H spin of water and the electron spin of a nitroxide radical-based label. Key features include the fact that only minute quantities (<10 ?l) and dilute (>=100 ?M) sample concentrations are needed. There is no size limit on the macromolecule or molecular assembly to be analyzed. Hydration water with translational correlation times between 10 and 800 ps is measured within ~10 Å distance of the spin label, encompassing the typical thickness of a hydration layer with three water molecules across. The hydration water moving within this time scale has significant implications, as this is what is modulated whenever macromolecules or molecular assemblies undergo interactions, binding or conformational changes. We demonstrate, with the examples of polymer complexation, protein aggregation and lipid-polymer interaction, that the measurements of interfacial hydration dynamics can sensitively and site specifically probe macromolecular interactions.

Ortony, Julia H.; Cheng, Chi-Yuan; Franck, John M.; Kausik, Ravinath; Pavlova, Anna; Hunt, Jasmine; Han, Songi

2011-01-01

139

Data Management System at the Photon Factory Macromolecular Crystallography Beamline  

NASA Astrophysics Data System (ADS)

Macromolecular crystallography is a very powerful tool to investigate three-dimensional structures of macromolecules at the atomic level, and is widely spread among structural biology researchers. Due to recent upgrades of the macromolecular crystallography beamlines at the Photon Factory, beamline throughput has improved, allowing more experiments to be conducted during a user's beam time. Although the number of beamlines has increased, so has the number of beam time applications. Consequently, both the experimental data from users' experiments and data derived from beamline operations have dramatically increased, causing difficulties in organizing these diverse and large amounts of data for the beamline operation staff and users. To overcome this problem, we have developed a data management system by introducing commercial middleware, which consists of a controller, database, and web servers. We have prepared several database projects using this system. Each project is dedicated to a certain aspect such as experimental results, beam time applications, beam time schedule, or beamline operation reports. Then we designed a scheme to link all the database projects.

Yamada, Y.; Matsugaki, N.; Chavas, L. M. G.; Hiraki, M.; Igarashi, N.; Wakatsuki, S.

2013-03-01

140

Protein Folding, Stability, and Solvation Structure in Osmolyte Solutions  

PubMed Central

An understanding of the impact of the crowded conditions in the cytoplasm on its biomolecules is of clear importance to biochemical, medical, and pharmaceutical science. Our previous work on the use of small biochemical compounds to crowd protein solutions indicates that a quantitative description of their nonideal behavior is possible and straightforward. Here, we show the structural origin of the nonideal solution behavior. We discuss the consequences of these findings regarding protein folding stability and solvation in crowded solutions through a structural analysis of the m-value or the change in free-energy difference of a macromolecule in solution with respect to the concentration of a third component. PMID:16113118

Rösgen, Jörg; Pettitt, B. Montgomery; Bolen, David Wayne

2005-01-01

141

On the elastica solution of a T3 tensegrity structure  

Microsoft Academic Search

Stability studies of a T3 tensegrity structure are performed. This structure is composed of three slender struts interconnected by six nonlinear elastic tendons and is prestressed. The struts are governed by linear constitutive laws and are allowed to buckle. Since tensegrity is used for modeling structures with quite large deformations, for example the cytoskeleton, and bifurcation theory—valid for small solutions

A. P. Pirentis; K. A. Lazopoulos

2006-01-01

142

Macromolecular and Dendrimer Based Magnetic Resonance Contrast Agents  

PubMed Central

Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20–25 years, a number of gadolinium based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution and targeting of dendrimer-based MR contrast agents are also discussed. PMID:20590365

Bumb, Ambika; Brechbiel, Martin W.; Choyke, Peter

2010-01-01

143

The Effect of Macromolecular Crowding, Ionic Strength and Calcium Binding on Calmodulin Dynamics  

PubMed Central

The flexibility in the structure of calmodulin (CaM) allows its binding to over 300 target proteins in the cell. To investigate the structure-function relationship of CaM, we combined methods of computer simulation and experiments based on circular dichroism (CD) to investigate the structural characteristics of CaM that influence its target recognition in crowded cell-like conditions. We developed a unique multiscale solution of charges computed from quantum chemistry, together with protein reconstruction, coarse-grained molecular simulations, and statistical physics, to represent the charge distribution in the transition from apoCaM to holoCaM upon calcium binding. Computationally, we found that increased levels of macromolecular crowding, in addition to calcium binding and ionic strength typical of that found inside cells, can impact the conformation, helicity and the EF hand orientation of CaM. Because EF hand orientation impacts the affinity of calcium binding and the specificity of CaM's target selection, our results may provide unique insight into understanding the promiscuous behavior of calmodulin in target selection inside cells. PMID:21829336

Wang, Qian; Liang, Kao-Chen; Czader, Arkadiusz; Waxham, M. Neal; Cheung, Margaret S.

2011-01-01

144

A theory of macromolecular chemotaxis.  

PubMed

A macromolecule in a gradient of a cosolute that is preferentially (relative to the solvent) either attracted to or excluded from the domain of the macromolecule should experience a thermodynamic force and move, respectively, up or down the gradient. A theory of chemotactic forces arising from such preferential interactions, especially short-range ligand binding and excluded volume interactions, is developed via an extension of Kirkwood-Buff theory. The ligand binding result is confirmed for both non-ionic and ionic cosolutes by standard solution thermodynamics. The effect of increasing the electrolyte concentration to diminish the electrostatic free energy of a charged macromolecule is also treated formally via an electrostatic macromolecule-electrolyte preferential interaction coefficient. For short-range interactions, the induced chemotactic velocity is attributed entirely to tangential tractions at the interface between the macromolecule and its surrounding solution. The velocity of a spherical macromolecule driven by such tractions is derived by a hydrodynamic calculation for steady-state creepy flow with a partial slip boundary condition. Qualitative comparisons of theoretical predictions with experimental observations of Zheng and Pollack pertaining to charged microspheres near the surfaces of non-ionic gels suggest that the reported exclusion zones are due to chemotaxis induced by gradients of base (NaOH) (or acid (HCl)) and salt. With a single adjustable parameter, namely, the ratio of slip length to area per surface carboxyl (or amidine) group, this theory yields nearly quantitative agreement with many observations. The estimated slip length for the microspheres is comparable to that obtained for bovine serum albumen by fitting the chemotactic theory to two reported cross-diffusion coefficients. When a solution with a gradient of NaOH is placed in contact with a smooth glass wall, chemotactic surface tractions are predicted to cause convection of the solution toward the acidic end of the gradient, as observed in preliminary experiments. PMID:23656252

Schurr, J Michael; Fujimoto, Bryant S; Huynh, Leticia; Chiu, Daniel T

2013-06-27

145

Water structure around dipeptides in aqueous solutions  

Microsoft Academic Search

The bulk water structure around small peptide fragments—glycyl-l-alanine, glycyl-l-proline and l-alanyl-l-proline—has been determined by a combination of neutron diffraction with isotopic substitution and empirical potential structural\\u000a refinement techniques. The addition of each of the dipeptides to water gives rise to decreased water–water coordination in\\u000a the surrounding water solvent. Additionally, both the Ow–Ow radial distribution functions and the water–water spatial density

Sylvia E. McLain; Alan K. Soper; Anthony Watts

2008-01-01

146

AFM studies of the nucleation and growth mechanisms of macromolecular crystals  

NASA Astrophysics Data System (ADS)

Atomic force microscopy (AFM) has been used to visualize events arising from the formation of intervening metastable phases at the surfaces of macromolecular crystals growing from solution. Crystals investigated were of the proteins canavalin, thaumatin, lipase, xylanase, and catalase, crystals of transfer RNA, and crystals of satellite tobacco mosaic virus. The appearance of aggregates on crystal surfaces was observed. The aggregates we infer to originate from liquid-protein droplets. These were particularly evident in freshly mixed mother liquor solutions. Droplets, upon sedimentation, have two possible fates. In some cases they immediately restructured as crystalline, multilayer stacks whose development was guided by, and contiguous with the underlying lattice. These contributed to the ordered growth of the crystal by serving as sources of growth steps. In other cases, liquid-protein droplets formed distinct microcrystals, somehow discontinuous with the underlying lattice, and these were subsequently incorporated into the growing substrate crystal. Scarring experiments with the AFM tip indicated that, detached from the crystal, molecules do not dissolve in the fluid phase but form metastable liquid-protein droplets with a potential to rapidly crystallize on the crystal surface. The molecular structure of the growth steps for thaumatin and lipase protein crystals were deduced. There is no step roughness due to thermal fluctuations, and each protein molecule which incorporated into the step edge remained. Growth steps propagate by addition of individual molecules which form subkinks of different size on the step edge.

Kuznetsov, Yu. G.; Malkin, A. J.; McPherson, A.

1999-01-01

147

Ultrafast electron transfer in riboflavin binding protein in macromolecular crowding of nano-sized micelle.  

PubMed

In this contribution, we have studied the dynamics of electron transfer (ET) of a flavoprotein to the bound cofactor, an important metabolic process, in a model molecular/macromolecular crowding environments. Vitamin B(2) (riboflavin, Rf) and riboflavin binding protein (RBP) are used as model cofactor and flavoprotein, respectively. An anionic surfactant sodium dodecyl sulfate (SDS) is considered to be model crowding agent. A systematic study on the ET dynamics in various SDS concentration, ranging from below critical micellar concentration (CMC), where the surfactants remain as monomeric form to above CMC, where the surfactants self-assemble to form nanoscopic micelle, explores the dynamics of ET in the model molecular and macromolecular crowding environments. With energy selective excitation in picosecond-resolved studies, we have followed temporal quenching of the tryptophan residue of the protein and Rf in the RBP-Rf complex in various degrees of molecular/macromolecular crowding. The structural integrity of the protein (secondary and tertiary structures) and the vitamin binding capacity of RBP have been investigated using various techniques including UV-Vis, circular dichroism (CD) spectroscopy and dynamic light scattering (DLS) studies in the crowding environments. Our finding suggests that the effect of molecular/macromolecular crowding could have major implication in the intra-protein ET dynamics in cellular environments. PMID:22930060

Rakshit, Surajit; Saha, Ranajay; Verma, Pramod Kumar; Mitra, Rajib Kumar; Pal, Samir Kumar

2012-12-01

148

Macromolecular Crystallization with Microfluidic Free-Interface Diffusion  

SciTech Connect

Fluidigm released the Topaz 1.96 and 4.96 crystallization chips in the fall of 2004. Topaz 1.96 and 4.96 are the latest evolution of Fluidigm's microfluidics crystallization technologies that enable ultra low volume rapid screening for macromolecular crystallization. Topaz 1.96 and 4.96 are similar to each other but represent a major redesign of the Topaz system and have of substantially improved ease of automation and ease of use, improved efficiency and even further reduced amount of material needed. With the release of the new Topaz system, Fluidigm continues to set the standard in low volume crystallization screening which is having an increasing impact in the field of structural genomics, and structural biology more generally. In to the future we are likely to see further optimization and increased utility of the Topaz crystallization system, but we are also likely to see further innovation and the emergence of competing technologies.

Segelke, B

2005-02-24

149

Use of Capillaries for Macromolecular Crystallization in a Cryogenic Dewar  

NASA Technical Reports Server (NTRS)

The enhanced gaseous nitrogen (EGN) dewar is a cryogenic dry shipper with a sealed cylinder inserted inside along with a temperature monitoring device, and is intended for macromolecular crystallization experiments on the International Space Station. Within the dewar, each crystallization experiment is contained as a solution within a plastic capillary tube. The standard procedure for loading samples in these tubes has involved rapid freezing of the precipitant and biomolecular solution, e.g., protein, directly in liquid nitrogen; this method, however, often resulted in uncontrolled formation of air voids, These air pockets, or bubbles, can lead to irreproducible crystallization results. A novel protocol has been developed to prevent formation of bubbles, and this has been tested in the laboratory as well as aboard the International Space Station during a 42-day long mission of July/August 2001. The gain or loss of mass from solutions within the plastic capillaries revealed that mass transport occurred among separated tubes, and that this mass transport was dependent upon the hygroscopic character of the solution contained in any given tube. The surface area of the plastic capillary tube also related to the observed mass transport. Furthermore, the decreased mass of solutions of-protein correlated to observed formation of protein crystals.

Ciszak, Ewa; Hammons, Aaron S.; Hong, Young Soo

2002-01-01

150

A shared structural solution for neutralizing ebolaviruses.  

PubMed

Sudan virus (genus Ebolavirus) is lethal, yet no monoclonal antibody is known to neutralize it. We here describe antibody 16F6 that neutralizes Sudan virus and present its structure bound to the trimeric viral glycoprotein. Unexpectedly, the 16F6 epitope overlaps that of KZ52, the only other antibody against the GP(1,2) core to be visualized to date. Furthermore, both antibodies against this crucial epitope bridging GP1-GP2 neutralize at a post-internalization step--probably fusion. PMID:22101933

Dias, João M; Kuehne, Ana I; Abelson, Dafna M; Bale, Shridhar; Wong, Anthony C; Halfmann, Peter; Muhammad, Majidat A; Fusco, Marnie L; Zak, Samantha E; Kang, Eugene; Kawaoka, Yoshihiro; Chandran, Kartik; Dye, John M; Saphire, Erica Ollmann

2011-12-01

151

A computational study of hydration, solution structure, and dynamics in dilute carbohydrate solutions  

E-print Network

A computational study of hydration, solution structure, and dynamics in dilute carbohydrate of the structure and dynamics of water near single carbohydrate molecules glucose, trehalose, and sucrose at 0 and 30 °C. The presence of a carbohydrate molecule has a number of significant effects on the microscopic

152

Crystal structure solution from experimentally determined atomic pair distribution functions  

Microsoft Academic Search

The paper describes an extension of the Liga algorithm for structure solution from atomic pair distribution function (PDF), to handle periodic crystal structures with multiple elements in the unit cell. The procedure is performed in 2 separate steps - at first the Liga algorithm is used to find unit cell sites consistent with pair distances extracted from the experimental PDF.

Pavol Juhas; Luke Granlund; Saurabh R. Gujarathi; Phillip M. Duxbury; Simon J. L. Billinge

2010-01-01

153

Type IV kerogens as analogues for organic macromolecular materials in aqueously altered carbonaceous chondrites.  

PubMed

Understanding the processes involved in the evolution of organic matter in the early Solar System requires extensive experimental work. The scientifically valuable carbonaceous chondrites are principal targets for organic analyses, but these meteorites are rare. Meteoritic analog materials available in larger quantities, on which experiments can be performed, would be highly beneficial. The bulk of the organic inventory of carbonaceous chondrites is made up of solvent-insoluble macromolecular material. This high-molecular-weight entity provides a record of thermal and aqueous parent-body alteration of precursor organic structures present at the birth of the Solar System. To identify an effective analogue for this macromolecular material, we analyzed a series of terrestrial kerogens by pyrolysis-gas chromatography-mass spectrometry. Type I and II kerogens are unsuitable analogues owing to their highly aliphatic nature. Type III kerogens show some similarities to meteoritic macromolecular materials but display a substantial biological heritage. Type IV kerogens, in this study derived from Mesozoic paleosols and produced by the reworking and oxidation of organic matter, represent an effective analogue. Some isomeric differences exist between meteoritic macromolecular materials and type IV kerogens, and stepped pyrolysis indicates variations in thermal stability. In addition to being a suitable material for novel experimentation, type IV kerogens also have the potential to aid in the optimization of instruments for deployment on Mars. PMID:23551239

Matthewman, Richard; Martins, Zita; Sephton, Mark A

2013-04-01

154

Assessment of the effect of macromolecular crowding on aggregation behaviour of a model amyloidogenic Peptide.  

PubMed

Accumulation of ordered protein aggregates (or amyloids) represents a hallmark of many diseases (e.g., Alzheimer's disease, type II diabetes, Parkinson's diseases etc.), results from intermolecular association of partially unfolded proteins/ peptides. Such associations usually take place in highly crowded conditions. The aggregates, which are formed under in vitro and in vivo conditions exhibit substantial variations in their structure and function. Such heterogeneities in amyloids might arise due to macromolecular crowding that is usually omitted under in vitro conditions. The current study is an attempt to assess the effects of macromolecular crowding on amyloid formation using a model amyloidogenic peptide. The sequence of the peptide was derived from C-terminal region (RATQIPSYKKLIMY) of PAP(248-286), which naturally occurs in human semen as amyloid aggregates and is known for boosting HIV infectivity. This model peptide forms sedimentable and fibrillar aggregates in aqueous buffer and shows the characteristic features of amyloids. In the presence of macromolecular crowders the morphological features of the amyloids are significantly altered and resulted in the formation of shorter amyloid aggregates. The current study assumes the hypothesis that macromolecular crowding in the biological system favours formation of heterogeneous classes of aggregates and each of them might differ in their biophysical and biological properties. PMID:25267253

Gaharwar, Bharti; Gour, Shalini; Kaushik, Vibha; Gupta, Nimisha; Kumar, Vijay; Hause, Gerd; Yadav, Jay Kant

2015-01-01

155

Iridescent solutions resulting from periodic structure of bilayer membranes. 2  

SciTech Connect

Iridescent aqueous solutions of dioctadecyldimethylammonium chloride (DOAC) have been newly found in the concentration range of 1-2 wt %. The structure of the solutions has been studied mainly by X-ray diffraction and ultraviolet and visible light reflection techniques and determined to be the lamellar liquid crystalline phase having the space distance of a submicrometer. The color appearance of the solutions results from diffraction of visible light by lamellar liquid crystalline structure of bilayer membranes. The mechanism of color appearance in DOAC solutions is the same as that of aqueous solutions of alkenylsuccinic acid, the structure of which is already elucidated by us. It is interesting to note, however, that the iridescent liquid crystalline phase of DOAC is understood to be thermodynamically metastable state, because of the following observations: (1) the iridescent-colored solutions can be obtained only by the sophisticated special procedures and (2) the color of the solutions disappears easily by weak agitations such as gentle shaking and/or stirring, and never recovers. It is worth noting, furthermore, in this DOAC system that the dramatic blue shift in the reflection spectra can be observed when the iridescent liquid crystal transforms into the gel phase on cooling. This blue-shift phenomenon might be due to the phase separation into iridescent gel and water phases on gelation processes. 15 refs., 6 figs.

Satoh, Naoki; Tsujii, Kaoru (Kao Corporation, Tochigi (Japan))

1992-02-01

156

Use of Capillaries for Macromolecular Crystallization in a Cryogenic Dewar  

NASA Technical Reports Server (NTRS)

The Enhanced Gaseous Nitrogen (EGN) Dewar is a cryogenic dry shipper with a sealed cylinder inserted inside along with a temperature-monitoring device, and is intended for macromolecular crystallization experiments on the International Space Station. Within the Dewar, each crystallization experiment is contained as a solution within a plastic capillary. The standard procedure for loading samples in these tubes has involved rapid freezing of the precipitant and biomolecule solution directly in liquid nitrogen; this method, however, often results in uncontrolled formation of air voids. These air pockets, or bubbles, then can lead to irreproducible crystallization results. A novel protocol has been developed to prevent formation of bubbles, and this has been tested in the laboratory as well as aboard the International Space Station during a 42-day long mission of July/August of 2001. Furthermore, gain or loss of mass from solutions within the capillaries revealed that mass transport amongst separated tubes occurred, and that this mass transport was determined by the hygroscopic character of a solution contained in any given tube. The sample volume and the surface area of the plastic capillary tube also related to the observed mass transport.

Ciszak, Ewa; Hammons, Aaron S.; Hong, Young Soo; Curreri, Peter A. (Technical Monitor)

2001-01-01

157

Revealing the macromolecular targets of complex natural products  

NASA Astrophysics Data System (ADS)

Natural products have long been a source of useful biological activity for the development of new drugs. Their macromolecular targets are, however, largely unknown, which hampers rational drug design and optimization. Here we present the development and experimental validation of a computational method for the discovery of such targets. The technique does not require three-dimensional target models and may be applied to structurally complex natural products. The algorithm dissects the natural products into fragments and infers potential pharmacological targets by comparing the fragments to synthetic reference drugs with known targets. We demonstrate that this approach results in confident predictions. In a prospective validation, we show that fragments of the potent antitumour agent archazolid A, a macrolide from the myxobacterium Archangium gephyra, contain relevant information regarding its polypharmacology. Biochemical and biophysical evaluation confirmed the predictions. The results obtained corroborate the practical applicability of the computational approach to natural product ‘de-orphaning’.

Reker, Daniel; Perna, Anna M.; Rodrigues, Tiago; Schneider, Petra; Reutlinger, Michael; Mönch, Bettina; Koeberle, Andreas; Lamers, Christina; Gabler, Matthias; Steinmetz, Heinrich; Müller, Rolf; Schubert-Zsilavecz, Manfred; Werz, Oliver; Schneider, Gisbert

2014-12-01

158

Topological Structure of Vortex Solution in Jackiw-Pi Model  

NASA Astrophysics Data System (ADS)

By using phi-mapping method, we discuss the topological structure of the self-duality solution in Jackiw-Pi model in terms of gauge potential decomposition. We set up relationship between Chern-Simons vortex solution and topological number, which is determined by Hopf index and Brouwer degree. We also give the quantization of flux in this case. Then, we study the angular momentum of the vortex, which can be expressed in terms of the flux.

Li, Xi-Guo; Liu, Zi-Yu; Li, Yong-Qing; Gao, Yuan; Guo, Yan-Rui; Xiao, Guo-Qing

2007-07-01

159

Exact coherent structures in pipe flow: travelling wave solutions  

Microsoft Academic Search

Three-dimensional travelling wave solutions are found for pressure-driven fluid flow through a circular pipe. They consist of three well-defined flow features streamwise rolls and streaks which dominate and streamwise-dependent wavy structures. The travelling waves can be classified by the m-fold rotational symmetry they possess about the pipe axis with m {=} 1,2,3,4,5 and 6 solutions identified. All are born out

H. Wedin; R. R. Kerswell

2004-01-01

160

The Yeast Exosome Functions as a Macromolecular Cage to Channel  

E-print Network

The Yeast Exosome Functions as a Macromolecular Cage to Channel RNA Substrates for Degradation.cell.2009.08.042 SUMMARY The exosome is a conserved macromolecular com- plex essential for RNA degradation. The nine-subunit core of the eukaryotic exosome shares a similar barrel-like architecture with prokaryotic

Bedwell, David M.

161

Anomalous structure factor of dense star polymer solutions  

E-print Network

The core-core structure factor of dense star polymer solutions in a good solvent is shown theoretically to exhibit an unusual behaviour above the overlap concentration. Unlike usual liquids, these solutions display a structure factor whose first peak decreases by increasing density while the second peak grows. The scenario repeats itself with the subsequent peaks as the density is further enhanced. For low enough arm numbers $f$ ($f \\leq 32$), various different considerations lead to the conclusion that the system remains fluid at all concentrations.

M. Watzlawek; H. Loewen; C. N. Likos

1998-06-22

162

Processes of ordered structure formation in polypeptide thin film solutions.  

SciTech Connect

An experimental study is presented on the hierarchical assembly of {alpha}-helical block copolymers polystyrene-poly({gamma}-benzyl-L-glutamate) into anisotropic ordered structures. We transformed thin solid films into solutions through exposure to solvent vapor and studied the nucleation and growth of ordered three-dimensional structures in such solutions, with emphasis on the dependence of these processes on supersaturation with respect to the solubility limit. Interestingly, polymer solubility could be significantly influenced via variation of humidity in the surrounding gas phase. It is concluded that the interfacial tension between the ordered structures and the solution increased with humidity. The same effect was observed for other protic non-solvents in the surrounding gas phase and is attributed to a complexation of poly({gamma}-benzyl-L-glutamate) by protic non-solvent molecules (via hydrogen-bonding interactions). This change of polymer solubility was demonstrated to be reversible by addition or removal of small amounts of protic non-solvent in the surrounding gas phase. At a constant polymer concentration, ordered ellipsoidal structures could be dissolved by removing water or methanol present in the solution. Such structures formed once again when water or methanol was reintroduced via the vapor phase.

Botiz, I.; Schlaad, H.; Reiter, G. (Center for Nanoscale Materials); (Max Planck Inst. of Colloids and Interfaces); (Univ. of Freiburg)

2010-06-17

163

Structure and rheology of associative triblocks in microemulsion solutions  

Microsoft Academic Search

This thesis describes our theoretical and experimental work on the rheology, static structure, and phase behavior of associative solutions. Our theoretical efforts have centered on solving the diffusion equation model of Dolan and Edwards for ideal associative triblocks between surfaces to yield the segment density profile and free energy. We have shown that polymers between two spheres cause an O(kT)

Surita Rani Bhatia

2000-01-01

164

Exact Coherent Structures in Pipe Flow: Travelling Wave Solutions  

E-print Network

1 Exact Coherent Structures in Pipe Flow: Travelling Wave Solutions H. Wedin & R.R. Kerswell pipe. They consist of three well-defined flow features - streamwise rolls and streaks which dominate. Introduction The stability of pressure-driven flow through a long circular pipe is one of the most classical

Burton, Geoffrey R.

165

Global solutions to the compressible Euler equations with geometrical structure  

Microsoft Academic Search

We prove the existence of global solutions to the Euler equations of compressible isentropic gas dynamics with geometrical structure, including transonic nozzle flow and spherically symmetric flow. Due to the presence of the geometrical source terms, the existence results themselves are new, especially as they pertain to radial flow in an unbounded region,\\u000a

Gui-Qiang Chen; James Glimm

1996-01-01

166

Numerical Solution of Singular ODE Eigenvalue Problems in Electronic Structure  

E-print Network

) Corresponding Author Email addresses: rh@cms.tuwien.ac.at (Robert Hammerling ), othmar@othmar-koch.org (Othmar: http://www.cms.tuwien.ac.at/ (Robert Hammerling ), http://www.othmar-koch.org (Othmar Koch ), httpNumerical Solution of Singular ODE Eigenvalue Problems in Electronic Structure Computations Robert

Koch, Othmar

167

Extended structure of rat islet amyloid polypeptide in solution.  

PubMed

The process of islet amyloid polypeptide (IAPP) formation and the prefibrillar oligomers are supposed to be one of the pathogenic agents causing pancreatic ?-cell dysfunction. The human IAPP (hIAPP) aggregates easily and therefore, it is difficult to characterize its structural features by standard biophysical tools. The rat version of IAPP (rIAPP) that differs by six amino acids when compared with hIAPP, is not prone to aggregation and does not form amyloid fibrils. Similar to hIAPP it also demonstrates random-coiled nature in solution. The structural propensity of rIAPP has been studied as a hIAPP mimic in recent works. However, the overall shape of it in solution still remains elusive. Using small angle X-ray scattering (SAXS) measurements combined with nuclear magnetic resonance (NMR) and molecular dynamics simulations (MD) the solution structure of rIAPP was studied. An unambiguously extended structural model with a radius of gyration of 1.83 nm was determined from SAXS data. Consistent with previous studies, an overall random-coiled feature with residual helical propensity in the N-terminus was confirmed. Combined efforts are necessary to unambiguously resolve the structural features of intrinsic disordered proteins. PMID:25387961

Wei, Lei; Jiang, Ping; Manimekalai, Malathy Sony Subramanian; Hunke, Cornelia; Grüber, Gerhard; Pervushin, Konstantin; Mu, Yuguang

2015-01-01

168

Structural and Spectroscopic Properties of Water Around Small Hydrophobic Solutes  

PubMed Central

We investigated the structural, dynamical and spectroscopic properties of water molecules around a solvated methane by means of Car-Parrinello molecular dynamics simulations. Despite their mobility, in the first-shell water molecules are dynamically displaced in a clathrate-like cage around the hydrophobic solute. No significant differences in water geometrical parameters, in molecular dipole moments or in hydrogen bonding properties are observed between in-shell and out-shell molecules, indicating that liquid water can accommodate a small hydrophobic solute without altering its structural properties. The calculated contribution of the first shell water molecules to the infrared spectra does not show significant differences with respect the bulk signal once the effects of the missing polarization of second-shell molecules has been taken into account. Small fingerprints of the clathrate-like structure appear in the vibrational density of states in the libration and OH stretching regions. PMID:22946539

Montagna, Maria; Sterpone, Fabio; Guidoni, Leonardo

2013-01-01

169

Empirical magnetic structure solution of frustrated spin systems.  

PubMed

Frustrated magnetism plays a central role in the phenomenology of exotic quantum states. However, since the magnetic structures of frustrated systems are often aperiodic, there has been the problem that they cannot be determined by using traditional crystallographic techniques. Here we show that the magnetic component of powder neutron scattering data is actually sufficiently information-rich to drive magnetic structure solution for frustrated systems, including spin ices, spin liquids, and molecular magnets. Our methodology employs ab initio reverse Monte Carlo refinement, making informed use of an additional constraint that minimizes variance in local spin environments. The atomistic spin configurations obtained in this way not only reflect a magnetic structure "solution" but also reproduce the full three-dimensional magnetic scattering pattern. PMID:22304284

Paddison, Joseph A M; Goodwin, Andrew L

2012-01-01

170

Electronic structures of Ascaris trypsin inhibitor in solution  

NASA Astrophysics Data System (ADS)

The electronic structures of Ascaris trypsin inhibitor in solution are obtained by the first-principles, all-electron, ab initio calculation using the self-consistent cluster-embedding (SCCE) method. The inhibitor, made up of 62 amino acid residues with 912 atoms, has two three-dimensional solution structures: 1ata and 1atb. The calculated ground-state energy of structure 1atb is lower than that of structure 1ata by 6.12 eV. The active sites are determined and explained: only structure 1atb has a N terminal at residue ARG+31. This shows that the structure 1atb is the stable and active form of the inhibitor, which is in agreement with the experimental results. The calculation reveals that some parts of the inhibitor can be easily changed while the inhibitor’s biological activity may be kept. This kind of information may be helpful in fighting viruses such as AIDS, SARS, and flu, since these viruses have higher variability. The calculation offers an independent theoretical estimate of the precision of structure determination.

Zheng, Haoping

2003-11-01

171

Solution superstructures: truncated cubeoctahedron structures of pyrogallol[4]arene nanoassemblies.  

PubMed

Giant nanocapsules: the solution-phase structures of PgC1Ho and PgC3Ho have been investigated using in situ neutron scattering measurements. The SANS results show the presence of spherical nanoassemblies of radius 18.2 Å, which are larger than the previously reported metal-seamed PgC3 hexamers (radius = 10 Å). The spherical architectures conform to a truncated cubeoctahedron geometry, indicating formation of the first metal-containing pyrogallol[4]arene-based dodecameric nanoassemblies in solution. PMID:24217564

Kumari, Harshita; Kline, Steven R; Fowler, Drew A; Mossine, Andrew V; Deakyne, Carol A; Atwood, Jerry L

2014-01-01

172

J. Phys. II FYance 7 (1997) 1597-1615 NOVEMBER 1997, PAGE 1597 Structure of Polymer Chains Confined in Vycor  

E-print Network

solutions; polymer melts; swelling PACS.82.70.-y Disperse systems Abstract. We observe by Small AngleJ. Phys. II FYance 7 (1997) 1597-1615 NOVEMBER 1997, PAGE 1597 Structure of Polymer Chains Confined Neutron scattering techniques (including small-angle scattering) PACS.61.25.Hq Macromolecular and polymer

Paris-Sud XI, Université de

173

Macromolecular prodrugs for controlled delivery of ribavirin.  

PubMed

Ribavirin (RBV)-containing polymers are synthesized based on poly(N-vinylpyrrolidone) and poly(acrylic acid), two polymers with extensive characterization in biomedicine. The copolymers are shown to exhibit a minor to negligible degree of association with erythrocytes, thus effectively eliminating the origin of the main side effects of RBV. The therapeutic benefit of macromolecular RBV prodrugs is illustrated by matched efficacy in suppressing production of nitric oxide by stimulated cultured macrophages as compared to pristine RBV with no associated cytotoxicity, which is in stark contrast to an RBV-based treatment which results in a significant decrease in cell viability. These results contribute to the development of antiviral polymer therapeutics and delivery of RBV in particular. PMID:24105953

Kryger, Mille B L; Smith, Anton A A; Wohl, Benjamin M; Zelikin, Alexander N

2014-02-01

174

Simulation and display of macromolecular complexes  

NASA Technical Reports Server (NTRS)

In association with an investigation of the interaction of proteins with DNA and RNA, an interactive computer program for building, manipulating, and displaying macromolecular complexes has been designed. The system provides perspective, planar, and stereoscopic views on the computer terminal display, as well as views for standard and nonstandard observer locations. The molecule or its parts may be rotated and/or translated in any direction; bond connections may be added or removed by the viewer. Molecular fragments may be juxtaposed in such a way that given bonds are aligned, and given planes and points coincide. Another subroutine provides for the duplication of a given unit such as a DNA or amino-acid base.

Nir, S.; Garduno, R.; Rein, R.; Macelroy, R. D.

1977-01-01

175

The spliceosome: a flexible, reversible macromolecular machine  

PubMed Central

With more than a hundred individual RNA and protein parts and a highly dynamic assembly and disassembly pathway, the spliceosome is arguably the most complicated macromolecular machine in the eukaryotic cell. This complexity has made kinetic and mechanistic analysis of splicing incredibly challenging. Yet recent technological advances are now providing tools for understanding this process in much greater detail. Ranging from genome-wide analyses of splicing and creation of an orthogonal spliceosome in vivo, to purification of active spliceosomes and observation of single molecules in vitro, such new experimental approaches are yielding significant insight into the inner workings of this remarkable machine. These experiments are rewriting the textbooks, with a new picture emerging of a dynamic, malleable machine heavily influenced by the identity of its pre-mRNA substrate. PMID:22480731

Hoskins, Aaron A.; Moore, Melissa J.

2012-01-01

176

Nitric Oxide Release Part I. Macromolecular Scaffolds  

PubMed Central

Summary The roles of nitric oxide (NO) in physiology and pathophysiology merit the use of NO as a therapeutic for certain biomedical applications. Unfortunately, limited NO payloads, too rapid NO release, and the lack of targeted NO delivery have hindered the clinical utility of NO gas and low molecular weight NO donor compounds. A wide-variety of NO-releasing macromolecular scaffolds has thus been developed to improve NO’s pharmacological potential. In this tutorial review, we provide an overview of the most promising NO release scaffolds including protein, organic, inorganic, and hybrid organic-inorganic systems. The NO release vehicles selected for discussion were chosen based on their enhanced NO storage, tunable NO release characteristics, and potential as therapeutics. PMID:22362355

Riccio, Daniel A.; Schoenfisch, Mark H.

2012-01-01

177

Solution of axisymmetric fluid structure interaction problems with NASTRAN  

NASA Technical Reports Server (NTRS)

The solution of axisymmetric acoustic fluid structure interaction problems, employing the NASTRAN computer program is presented. A previously developed 3-D Cartesian Coordinates pressure element formulation is adapted especially for axisymmetric elements. Analogous to the 3-D Cartesian Coordinate predecessor, the fluid portion of the problem is modeled with finite elements wherein one of the displacement components serves as a dummy variable for the pressure unknowns. Two alternatives for implementation of the analogy are presented: (1) an approximate method by which dummy values of G, and nu are used to approximately invoke the analogy wherein the accuracy of the approximation is made as close as desired to the proper analogy within an arbitrary small parameter epsiton; (2) an exact method whereby the NASTRAN FORTRAN coding is slightly changed to invoke the analogy exactly. Comparison of the finite element solution to the exact solution to the same problem is given.

Kalinowski, A. J.; Nebelung, C. W.

1982-01-01

178

Radiation damage in macromolecular crystallography: what is it and why should we care?  

PubMed Central

Radiation damage inflicted during diffraction data collection in macromolecular crystallography has re-emerged in the last decade as a major experimental and computational challenge, as even for crystals held at 100?K it can result in severe data-quality degradation and the appearance in solved structures of artefacts which affect biological interpretations. Here, the observable symptoms and basic physical processes involved in radiation damage are described and the concept of absorbed dose as the basic metric against which to monitor the experimentally observed changes is outlined. Investigations into radiation damage in macromolecular crystallography are ongoing and the number of studies is rapidly increasing. The current literature on the subject is compiled as a resource for the interested researcher. PMID:20382986

Garman, Elspeth F.

2010-01-01

179

Effect of Ternary Solutes on the Evolution of Structure and Gel Formation in Amphiphilic Copolymer Solutions  

NASA Astrophysics Data System (ADS)

Aqueous solutions of polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) amphiphilic triblock copolymers (commercially known as Pluronic surfactants) undergo reversible and temperature-dependent micellization and arrangement into cubic ordered lattices known as "micelle gels". The macroscopic behavior of the ordering is a transition from a liquid to a gel. While the phase behavior and gel structure of pure Pluronic surfactant solutions have been well studied, less is known about the effects of added ternary solutes. In this dissertation, a comprehensive investigation into the effects of the added pharmaceutical methylparaben on solutions of F127 ranging from 10 to 30 wt% was conducted in order to better understand the behavior of F127 in multicomponent pharmaceutical formulations. The viscoelastic properties of F127 gel formation were studied using rheometry, where heating rates of 0.1, 1, and 10 degrees C/min were also used to probe the kinetics of the gel transition. In solutions containing methylparaben, F127 gelation occurred at up to 15 degrees C lower temperatures and was accelerated by a factor of three to four. Small angle x-ray scattering (SAXS) was used to characterize the structure of the ordered domains, and how they were affected by the presence of dissolved pharmaceuticals. It was found that ordered domain formation changed from heterogeneous nucleation and growth to possible homogeneous nucleation and growth. A roughly 2% reduction in the cubic lattice parameter was also observed for solutions containing methylparaben. Differential scanning calorimetry (DSC) experiments were performed on a series of different Pluronic surfactants in order to characterize the micellization behavior as a function of PPO center block length and PEO/PPO ratio. Added methylparaben suppressed the micellization endotherm, the degree of suppression depending linearly on the amount of added methylparaben, as well as the length of the PPO center block and PEO/PPO ratio. This dissertation yielded a thorough characterization of the changes in micellization and gelation behavior in F127 gels as a result of added pharmaceuticals. Previously unobserved behavior such as the onset of ordered domain formation in F127 gels was observed, and a greater understanding of the interactions between amphiphilic copolymer solutions and dissolved solutes was achieved.

Meznarich, Norman Anthony Kang

180

Small-angle X-ray scattering on biological macromolecules and nanocomposites in solution.  

PubMed

Small-angle X-ray scattering (SAXS) is a powerful method to study the structural properties of materials at the nanoscale. Recent progress in instrumentation and analysis methods has led to rapidly growing applications of this technique for the characterization of biological macromolecules in solution. Ab initio and rigid-body modeling methods allow one to build three-dimensional, low-resolution models from SAXS data. With the new approaches, oligomeric states of proteins and macromolecular complexes can be assessed, chemical equilibria and kinetic reactions can be studied, and even flexible objects such as intrinsically unfolded proteins can be quantitatively characterized. This review describes the analysis methods of SAXS data from macromolecular solutions, ranging from the computation of overall structural parameters to advanced three-dimensional modeling. The efficiency of these methods is illustrated by recent applications to biological macromolecules and nanocomposite particles. PMID:23216378

Blanchet, Clement E; Svergun, Dmitri I

2013-01-01

181

Small-Angle X-Ray Scattering on Biological Macromolecules and Nanocomposites in Solution  

NASA Astrophysics Data System (ADS)

Small-angle X-ray scattering (SAXS) is a powerful method to study the structural properties of materials at the nanoscale. Recent progress in instrumentation and analysis methods has led to rapidly growing applications of this technique for the characterization of biological macromolecules in solution. Ab initio and rigid-body modeling methods allow one to build three-dimensional, low-resolution models from SAXS data. With the new approaches, oligomeric states of proteins and macromolecular complexes can be assessed, chemical equilibria and kinetic reactions can be studied, and even flexible objects such as intrinsically unfolded proteins can be quantitatively characterized. This review describes the analysis methods of SAXS data from macromolecular solutions, ranging from the computation of overall structural parameters to advanced three-dimensional modeling. The efficiency of these methods is illustrated by recent applications to biological macromolecules and nanocomposite particles.

Blanchet, Clement E.; Svergun, Dmitri I.

2013-04-01

182

Flavin adenine dinucleotide structural motifs: from solution to gas phase.  

PubMed

Flavin adenine dinucleotide (FAD) is involved in important metabolic reactions where the biological function is intrinsically related to changes in conformation. In the present work, FAD conformational changes were studied in solution and in gas phase by measuring the fluorescence decay time and ion-neutral collision cross sections (CCS, in a trapped ion mobility spectrometer, TIMS) as a function of the solvent conditions (i.e., organic content) and gas-phase collisional partner (i.e., N2 doped with organic molecules). Changes in the fluorescence decay suggest that FAD can exist in four conformations in solution, where the abundance of the extended conformations increases with the organic content. TIMS-MS experiments showed that FAD can exist in the gas phase as deprotonated (M = C27H31N9O15P2) and protonated forms (M = C27H33N9O15P2) and that multiple conformations (up to 12) can be observed as a function of the starting solution for the [M + H](+) and [M + Na](+)molecular ions. In addition, changes in the relative abundances of the gas-phase structures were observed from a "stack" to a "close" conformation when organic molecules were introduced in the TIMS cell as collision partners. Candidate structures optimized at the DFT/B3LYP/6-31G(d,p) were proposed for each IMS band, and results showed that the most abundant IMS band corresponds to the most stable candidate structure. Solution and gas-phase experiments suggest that the driving force that stabilizes the different conformations is based on the interaction of the adenine and isoalloxazine rings that can be tailored by the "solvation" effect created with the organic molecules. PMID:25222439

Molano-Arevalo, Juan Camilo; Hernandez, Diana R; Gonzalez, Walter G; Miksovska, Jaroslava; Ridgeway, Mark E; Park, Melvin A; Fernandez-Lima, Francisco

2014-10-21

183

JBluIce-EPICS control system for macromolecular crystallography.  

SciTech Connect

The trio of macromolecular crystallography beamlines constructed by the General Medicine and Cancer Institutes Collaborative Access Team (GM/CA-CAT) in Sector 23 of the Advanced Photon Source (APS) have been in growing demand owing to their outstanding beam quality and capacity to measure data from crystals of only a few micrometres in size. To take full advantage of the state-of-the-art mechanical and optical design of these beamlines, a significant effort has been devoted to designing fast, convenient, intuitive and robust beamline controls that could easily accommodate new beamline developments. The GM/CA-CAT beamline controls are based on the power of EPICS for distributed hardware control, the rich Java graphical user interface of Eclipse RCP and the task-oriented philosophy as well as the look and feel of the successful SSRL BluIce graphical user interface for crystallography. These beamline controls feature a minimum number of software layers, the wide use of plug-ins that can be written in any language and unified motion controls that allow on-the-fly scanning and optimization of any beamline component. This paper describes the ways in which BluIce was combined with EPICS and converted into the Java-based JBluIce, discusses the solutions aimed at streamlining and speeding up operations and gives an overview of the tools that are provided by this new open-source control system for facilitating crystallographic experiments, especially in the field of microcrystallography.

Stepanov, S.; Makarov, O.; Hilgart, M.; Pothineni, S.; Urakhchin, A.; Devarapalli, S.; Yoder, D.; Becker, M.; Ogata, C.; Sanishvili, R.; Nagarajan, V.; Smith, J. L.; Fischetti, R. F. (Biosciences Division); (Univ. of Michigan)

2011-01-01

184

Present status of SPring-8 macromolecular crystallography beamlines  

SciTech Connect

Seven beamlines are operated for macromolecular crystallography (MX) at SPring-8. The three undulator beamlines are developed for cutting edge target and four bending-magnet beamlines are developed for high throughput MX. The undulator beamline, BL41XU that provides the most brilliant beam, is dedicated to obtain high quality data even from small-size and weakly-diffracting crystals. The minimum beam size at sample position is achieved to 10 {mu}m diameter using a pin-hole collimator. Its photon flux at wavelength {lambda} = 1.0 A is 2.8x10{sup 11} photons/sec. This small beam coupled with irradiation point scanning method is quite useful to take diffraction dataset from small crystals by suppressing the radiation damage. These advanced technologies made a number of difficult protein structure analysis possible, (i.e. Sodium-potassium ATPase). The bending-magnet beamlines BL26B1/B2 and BL38B1 provide automatic data collection exploiting the high mobility of the beam. The beamline operation software 'BSS', sample auto-changer 'SPACE' and web-based data management software 'D-Cha' have made the automatic data collection possible. The 'Mail-in data collection system' that accepts distant users samples via courier service have made users possible to collect diffraction data without visiting SPring-8. The structural genomics research is promoted by these beamlines.

Kawano, Yoshiaki; Hirata, Kunio; Ueno, Go; Hikima, Takaaki; Murakami, Hironori; Maeda, Daisuke; Nisawa, Atsushi; Yamamoto, Masaki [RIKEN SPring-8 Center, 1-1-1, Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Shimizu, Nobutaka; Baba, Seiki; Hasegawa, Kazuya; Makino, Masatomo; Mizuno, Nobuhiro; Hoshino, Takeshi; Ito, Ren; Wada, Izumi; Kumasaka, Takashi [JASRI/SPring-8, 1-1-1, Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan)

2010-06-23

185

Solution structure and dynamics of bovine beta-lactoglobulin A.  

PubMed Central

Using heteronuclear NMR spectroscopy, we studied the solution structure and dynamics of bovine beta-lactoglobulin A at pH 2.0 and 45 degrees C, where the protein exists as a monomeric native state. The monomeric NMR structure, comprising an eight-stranded continuous antiparallel beta-barrel and one major alpha-helix, is similar to the X-ray dimeric structure obtained at pH 6.2, including betaI-strand that forms the dimer interface and loop EF that serves as a lid of the interior hydrophobic hole. [1H]-15N NOE revealed that betaF, betaG, and betaH strands buried under the major alpha-helix are rigid on a pico- to nanosecond time scale and also emphasized rapid fluctuations of loops and the N- and C-terminal regions. PMID:10595563

Kuwata, K.; Hoshino, M.; Forge, V.; Era, S.; Batt, C. A.; Goto, Y.

1999-01-01

186

Brownian Dynamics Simulation of Protein Solutions: Structural and Dynamical Properties  

PubMed Central

The study of solutions of biomacromolecules provides an important basis for understanding the behavior of many fundamental cellular processes, such as protein folding, self-assembly, biochemical reactions, and signal transduction. Here, we describe a Brownian dynamics simulation procedure and its validation for the study of the dynamic and structural properties of protein solutions. In the model used, the proteins are treated as atomically detailed rigid bodies moving in a continuum solvent. The protein-protein interaction forces are described by the sum of electrostatic interaction, electrostatic desolvation, nonpolar desolvation, and soft-core repulsion terms. The linearized Poisson-Boltzmann equation is solved to compute electrostatic terms. Simulations of homogeneous solutions of three different proteins with varying concentrations, pH, and ionic strength were performed. The results were compared to experimental data and theoretical values in terms of long-time self-diffusion coefficients, second virial coefficients, and structure factors. The results agree with the experimental trends and, in many cases, experimental values are reproduced quantitatively. There are no parameters specific to certain protein types in the interaction model, and hence the model should be applicable to the simulation of the behavior of mixtures of macromolecules in cell-like crowded environments. PMID:21112303

Mereghetti, Paolo; Gabdoulline, Razif R.; Wade, Rebecca C.

2010-01-01

187

Brownian Dynamics Simulation of Protein Solutions: Structural and Dynamical Properties  

SciTech Connect

The study of solutions of biomacromolecules provides an important basis for understanding the behavior of many fundamental cellular processes, such as protein folding, self-assembly, biochemical reactions, and signal transduction. Here, we describe a Brownian dynamics simulation procedure and its validation for the study of the dynamic and structural properties of protein solutions. In the model used, the proteins are treated as atomically detailed rigid bodies moving in a continuum solvent. The protein-protein interaction forces are described by the sum of electrostatic interaction, electrostatic desolvation, nonpolar desolvation, and soft-core repulsion terms. The linearized Poisson-Boltzmann equation is solved to compute electrostatic terms. Simulations of homogeneous solutions of three different proteins with varying concentrations, pH, and ionic strength were performed. The results were compared to experimental data and theoretical values in terms of long-time self-diffusion coefficients, second virial coefficients, and structure factors. The results agree with the experimental trends and, in many cases, experimental values are reproduced quantitatively. There are no parameters specific to certain protein types in the interaction model, and hence the model should be applicable to the simulation of the behavior of mixtures of macromolecules in cell-like crowded environments.

Mereghetti, Paolo; Gabdoulline, Razif; Wade, Rebecca C.

2010-12-01

188

Changes in electronic structure of copper films in aqueous solutions  

NASA Astrophysics Data System (ADS)

The possibilities for using x-ray absorption spectroscopy (XAS) and resonant inelastic x-ray scattering (RIXS) to probe the Cu oxidation state and changes in the electronic structure during interaction between copper and ground-water solutions were examined. Surface modifications induced by chemical reactions of oxidized 100 Å Cu films with Cl-, SO42- and HCO3- ions in aqueous solutions with various concentrations were studied in situ using liquid cells. Copper corrosion processes in ground water were monitored for up to nine days. By comparing Cu 2p-3d, 4s transitions for a number of reference substances previously measured, changes in electronic structure of the Cu films were analysed. The XAS and RIXS spectral shape at the Cu edge, the chemical shift of the main line for Cu2+, and the energy positions of the observed satellites served as a tool for monitoring the changes during the reaction. It was found that the pH value and the Cl- concentration in solutions strongly affect the speed of the corrosion reaction.

Kvashnina, K. O.; Butorin, S. M.; Modin, A.; Soroka, I.; Marcellini, M.; Guo, J.-H.; Werme, L.; Nordgren, J.

2007-06-01

189

Lysozyme Protein Solution with an Intermediate Range Order Structure  

SciTech Connect

The formation of equilibrium clusters has been studied in both a prototypical colloidal system and protein solutions. The appearance of a low-Q correlation peak in small angle scattering patterns of lysozyme solution was attributed to the cluster-cluster correlation. Consequently, the presence of long-lived clusters has been established. By quantitatively analyzing both the SANS (small angle neutron scattering) and NSE (neutron spin echo) data of lysozyme solution using statistical mechanics models, we conclusively show in this paper that the appearance of a low-Q peak is not a signature of the formation of clusters. Rather, it is due to the formation of an intermediate range order structure governed by a short-range attraction and a long-range repulsion. We have further studied dynamic features of a sample with high enough concentration at which clusters are formed in solution. From the estimation of the mean square displacement by using short-time and long-time diffusion coefficient measured by NSE and NMR, we find that these clusters are not permanent but have a finite lifetime longer than the time required to diffuse over a distance of a monomer diameter.

Liu, Yun [National Institute of Standards and Technology (NIST); Porcar, L. [National Institute of Standards and Technology (NIST); Chen, Wei-Ren [ORNL; Chen, Jinhong [Memorial Sloan-Kettering Cancer Center; Falus, Peter [ORNL; Fratini, Emiliano [University of Florence; Faraone, Antonio [National Institute of Standards and Technology (NIST); Baglioni, P [University of Florence

2011-01-01

190

The use of a mini-? goniometer head in macromolecular crystallography diffraction experiments  

PubMed Central

Most macromolecular crystallography (MX) diffraction experiments at synchrotrons use a single-axis goniometer. This markedly contrasts with small-molecule crystallography, in which the majority of the diffraction data are collected using multi-axis goniometers. A novel miniaturized ?-gonio­meter head, the MK3, has been developed to allow macromolecular crystals to be aligned. It is available on the majority of the structural biology beamlines at the ESRF, as well as elsewhere. In addition, the Strategy for the Alignment of Crystals (STAC) software package has been developed to facilitate the use of the MK3 and other similar devices. Use of the MK3 and STAC is streamlined by their incorporation into online analysis tools such as EDNA. The current use of STAC and MK3 on the MX beamlines at the ESRF is discussed. It is shown that the alignment of macromolecular crystals can result in improved diffraction data quality compared with data obtained from randomly aligned crystals. PMID:23793150

Brockhauser, Sandor; Ravelli, Raimond B. G.; McCarthy, Andrew A.

2013-01-01

191

Macromolecular shape and interactions in layer-by-layer assemblies within cylindrical nanopores  

PubMed Central

Summary Layer-by-layer (LbL) deposition of polyelectrolytes and proteins within the cylindrical nanopores of anodic aluminum oxide (AAO) membranes was studied by optical waveguide spectroscopy (OWS). AAO has aligned cylindrical, nonintersecting pores with a defined pore diameter d 0 and functions as a planar optical waveguide so as to monitor, in situ, the LbL process by OWS. The LbL deposition of globular proteins, i.e., avidin and biotinylated bovine serum albumin was compared with that of linear polyelectrolytes (linear-PEs), both species being of similar molecular weight. LbL deposition within the cylindrical AAO geometry for different pore diameters (d 0 = 25–80 nm) for the various macromolecular species, showed that the multilayer film growth was inhibited at different maximum numbers of LbL steps (n max). The value of n max was greatest for linear-PEs, while proteins had a lower value. The cylindrical pore geometry imposes a physical limit to LbL growth such that n max is strongly dependent on the overall internal structure of the LbL film. For all macromolecular species, deposition was inhibited in native AAO, having pores of d 0 = 25–30 nm. Both, OWS and scanning electron microscopy showed that LbL growth in larger AAO pores (d 0 > 25–30 nm) became inhibited when approaching a pore diameter of d eff,n_max = 25–35 nm, a similar size to that of native AAO pores, with d 0 = 25–30 nm. For a reasonable estimation of d eff,n_max, the actual volume occupied by a macromolecular assembly must be taken into consideration. The results clearly show that electrostatic LbL allowed for compact macromolecular layers, whereas proteins formed loosely packed multilayers. PMID:23019541

Lazzara, Thomas D; Lau, K H Aaron; Knoll, Wolfgang; Janshoff, Andreas

2012-01-01

192

The solution structure of the Josephin domain of ataxin-3: Structural determinants for molecular recognition  

Microsoft Academic Search

The Josephin domain plays an important role in the cellular functions of ataxin-3, the protein responsible for the neurodegenerative Machado-Joseph disease. We have determined the solution structure of Josephin and shown that it belongs to the family of papain-like cysteine proteases, sharing the highest degree of structural similarity with bacterial staphopain. A currently unique structural feature of Josephin is a

Giuseppe Nicastro; Rajesh P. Menon; Laura Masino; Philip P. Knowles; Neil Q. McDonald; Annalisa Pastore

2005-01-01

193

Solution and surface effects on plasma fibronectin structure.  

PubMed

As assessed by electron microscopy, the reported shape of the plasma fibronectin molecule ranges from that of a compact particle to an elongated, rod-like structure. In this study, we evaluated the effects of solution and surface conditions on fibronectin shape. Freeze-dried, unstained human plasma fibronectin molecules deposited at pH 7.0-7.4 onto carbon films and examined by scanning transmission electron microscopy appeared relatively compact and pleiomorphic, with approximate average dimensions of 24 nm X 16 nm. Negatively stained molecules also had a similar shape but revealed greater detail in that we observed irregular, yarn-like structures. Glutaraldehyde-induced intramolecular cross-linking did not alter the appearance of plasma fibronectin. Molecules deposited at pH 2.8, pH 9.3, or after succinylation were less compact than those deposited at neutral pH. In contrast, fibronectin molecules sprayed onto mica surfaces at pH 7, rotary shadowed, and examined by transmission electron microscopy were elongated and nodular with a contour length of 120-130 nm. Sedimentation velocity experiments and electron microscopic observations indicate that fibronectin unfolds when it is succinylated, when the ionic strength is raised at pH 7, or when the pH is adjusted to 9.3 or 2.8. Greater unfolding is observed at pH 2.8 at low ionic strength (less than 0.01) compared with material at that pH in 0.15 M NaCl solution. We conclude that (a) the shape assumed by the fibronectin molecule can be strongly affected by solution conditions and by deposition onto certain surfaces; and that (b) the images of fibronectin seen by scanning transmission electron microscopy at neutral pH on carbon film are representative of molecules in physiologic solution. PMID:6417145

Tooney, N M; Mosesson, M W; Amrani, D L; Hainfeld, J F; Wall, J S

1983-12-01

194

Understanding the defect structure of solution grown zinc oxide  

NASA Astrophysics Data System (ADS)

Zinc oxide (ZnO) is a wide bandgap semiconducting oxide with many potential applications in various optoelectronic devices such as light emitting diodes (LEDs) and field effect transistors (FETs). Much effort has been made to understand the ZnO structure and its defects. However, one major issue in determining whether it is Zn or O deficiency that provides ZnO its unique properties remains. X-ray absorption spectroscopy (XAS) is an ideal, atom specific characterization technique that is able to probe defect structure in many materials, including ZnO. In this paper, comparative studies of bulk and aqueous solution grown (?90 °C) ZnO powders using XAS and x-ray pair distribution function (XPDF) techniques are described. The XAS Zn-Zn correlation and XPDF results undoubtedly point out that the solution grown ZnO contains Zn deficiency, rather than the O deficiency that were commonly reported. This understanding of ZnO short range order and structure will be invaluable for further development of solid state lighting and other optoelectronic device applications.

Liew, Laura-Lynn; Sankar, Gopinathan; Handoko, Albertus D.; Goh, Gregory K. L.; Kohara, Shinji

2012-05-01

195

Structure determination of zinc iodide complexes formed in aqueous solution  

Microsoft Academic Search

Structures of the complexes formed in aqueous solutions between zinc(II) and iodide ions have been determined from large-angle X-ray scattering, Raman and far-IR measurements. The coordination in the hydrated Zn2+ hexaaqua ion and the first iodide complex, [ZnI]+, is octahedral, but is changed into tetrahedral in the higher complexes, [ZnI2(H2O)2], [ZnI3(H2O)]- and [ZnI4]2-. The Zn-I bond length is 2.635(4)Å in

Hisanobu Wakita; Georg Johansson; Magnus Sandström; Peter L. Goggin; Hitoshi Ohtaki

1991-01-01

196

Three-dimensional solution structure of Escherichia coli periplasmic cyclophilin.  

PubMed

The solution structure of the periplasmic cyclophilin type cis-trans peptidyl-prolyl isomerase from Escherichia coli (167 residues, MW > 18.200) has been determined using multidimensional heteronuclear NMR spectroscopy and distance geometry calculations. The structure determination is based on a total of 1720 NMR-derived restraints (1566 distance and 101 phi and 53 chi 1 torsion angle restraints). Twelve distance geometry structures were calculated, and the average root-mean-square (rms) deviation about the mean backbone coordinate positions is 0.84 +/- 0.18 A for the backbone atoms of residues 5-165 of the ensemble. The three-dimensional structure of E. coli cyclophilin consists of an eight-stranded antiparallel beta-sheet barrel capped by alpha-helices. The average coordinates of the backbone atoms of the core residues of E. coli cyclophilin have an rms deviation of 1.44 A, with conserved regions in the crystal structure of unligated human T cell cyclophilin [Ke, H. (1992) J. Mol. Biol. 228, 539-550]. Four regions proximal to the active site differ substantially and may determine protein substrate specificity, sensitivity to cyclosporin A, and the composite drug:protein surface required to inhibit calcineurin. A residue essential for isomerase activity in human T cell cyclophilin (His126) is replaced by Tyr122 in E. coli cyclophilin without affecting enzymatic activity. PMID:8130188

Clubb, R T; Ferguson, S B; Walsh, C T; Wagner, G

1994-03-15

197

A Beam line for Macromolecular Crystallography in ALBA  

SciTech Connect

ALBA is a third generation 3 GeV storage ring being built near Barcelona and foreseen to be operational in 2010. Out of the seven beamlines already funded in ALBA, one will be dedicated to macromolecular crystallography (MX). The beamline, dubbed XALOC, shall cope with a broad range of crystal structures and sizes. To this aim, a flexible optical design involving variable focusing optics has been incorporated into the beamline optics. The photon source will be a 2 m long, in-vacuum undulator with a period of 21.3 mm. The optics will consist in a Si(111), double-crystal monochromator cryogenically cooled, and a pair of mirrors placed in a Kirkpatrick-Baez configuration. The beamline will deliver a high flux beam in the 5-15 keV energy range, with an energy resolution of {delta}E/E {approx}2 x 10-4. In addition to the main beamline, it is being considered the possibility to use a diamond laue monochromator to provide photons at a fixed wavelength to an ancillary branch. This report shows the present status of the beamline design.

Juanhuix, Jordi; Ferrer, Salvador [CELLS -ALBA Synchrotron, Ed. Ciencies, Campus UAB, 08193 Bellaterra, Barcelona (Spain)

2007-01-19

198

UMass Morph Server: Macromolecular Dynamics Analyses Using Elastic Network Models.  

PubMed

The geometry-based mechanical models called elastic network models (ENMs) in various resolutions have been developed for the study of macromolecular motions. In a coarse-grained ENM, a biological system is represented as a network of springs connecting representative points. They range from single atoms to functional domains depending on the level of details in modeling. In this paper presented are the various kinds of coarse-graining methods such as symmetry-constrained, rigid-cluster, and hybrid ENMs. They enable us to overcome the computational burden and memory limitation in the conventional molecular dynamics (MD) simulations and full-atom normal mode analysis (NMA) without loss of generality. For the broad impact of this work on the structural biology area we also develop the UMass Morph Server (UMMS). Based on the requests from online users, UMMS does not only serve a harmonic NMA that describes thermal behaviors (i.e., fluctuations) of a macromolecule around its equilibrium state, but also generates anharmonic transition pathways between two end conformations by using the elastic network interpolation (ENI) also developed by the author. In addition, UMMS can provide two unique features as follows: (i) interpretation of massive MD data by finding essential pathways (ii) the conformation prediction incorporated with time-resolved information such as FRET data. Many example movies and numeric data can be downloadable at http://biomechanics.ecs.umass.edu/umms.html. PMID:17282770

Jang, Yunho; Kim, Moon

2005-01-01

199

Remote Access to the PXRR Macromolecular Crystallography Facilities at the NSLS  

SciTech Connect

The most recent surge of innovations that have simplified and streamlined the process of determining macromolecular structures by crystallography owes much to the efforts of the structural genomics community. However, this was only the last step in a long evolution that saw the metamorphosis of crystallography from an heroic effort that involved years of dedication and skill into a straightforward measurement that is occasionally almost trivial. Many of the steps in this remarkable odyssey involved reducing the physical labor that is demanded of experimenters in the field. Other steps reduced the technical expertise required for conducting those experiments.

A Soares; D Schneider; J Skinner; M Cowan; R Buono; H Robinson; A Heroux; M Carlucci-Dayton; A Saxena; R Sweet

2011-12-31

200

Structure of alamethicin in solution: nuclear magnetic resonance relaxation studies.  

PubMed

An NMR relaxation study at 500 MHz of the icosapeptide antibiotic alamethicin is reported. This study lends further support to the partly helical, partly extended, amphiphilic, and dimeric structure recently proposed for this peptide in methanolic solutions [Banerjee, U., Tsui, F. P., Balasubramanian, T. N., Marshall, G. R., & Chan, S. I. (1983) J. Mol. Biol. 165, 757]. The N-acetyl methyl groups toward the N terminus of alamethicin in this solvent system were found to exhibit unusual NMR relaxation behavior. The decay of the transverse magnetization due to these protons was nonexponential, but the spin-lattice relaxation recovery of the longitudinal magnetization was exponential. In a solution saturated with urea, however, both decays were exponential. These observations are shown to be consistent with the proposed structure. Studies in water yielded qualitatively similar but more complex results. The transverse relaxation times suggest further aggregation in water and indicate that the larger aggregates in water may be made up of the smaller units observed in methanol. PMID:6615794

Banerjee, U; Chan, S I

1983-07-19

201

Aqueous Solutions on Silica Surfaces: Structure and Dynamics from Simulations  

NASA Astrophysics Data System (ADS)

Our group is interested in understanding the properties of aqueous electrolyte solutions at interfaces. The fundamental questions we seek to answer include: (A) how does a solid structure perturb interfacial water? (B) How far from the solid does this perturbation persist? (C) What is the rate of water reorientation and exchange in the perturbed layer? (D) What happens in the presence of simple electrolytes? To address such topics we implemented atomistic molecular dynamics simulations. Recent results for water and simple electrolytes near silicon dioxide surfaces of various degrees of hydroxylation will be presented. The data suggest the formation of a layered aqueous structure near the interface. The density profile of interfacial water seems to dictate the density profiles of aqueous solutions containing NaCl, CaCl2, CsCl, and SrCl2 near the solid surfaces. These results suggest that ion-ion and ion-water correlations are extremely important factors that should be considered when it is desired to predict the distribution of electrolytes near a charged surface. Our results will benefit a number of practical applications including water desalination, exploitation of the oil shale in the Green River Basin, nuclear waste sites remediation, and design of nanofluidic devices.

Striolo, Alberto; Argyris, Dimitrios; Tummala, Naga Rajesh

2009-03-01

202

Solution structure of the core SMN–Gemin2 complex  

PubMed Central

In humans, assembly of spliceosomal snRNPs (small nuclear ribonucleoproteins) begins in the cytoplasm where the multi-protein SMN (survival of motor neuron) complex mediates the formation of a seven-membered ring of Sm proteins on to a conserved site of the snRNA (small nuclear RNA). The SMN complex contains the SMN protein Gemin2 and several additional Gemins that participate in snRNP biosynthesis. SMN was first identified as the product of a gene found to be deleted or mutated in patients with the neurodegenerative disease SMA (spinal muscular atrophy), the leading genetic cause of infant mortality. In the present study, we report the solution structure of Gemin2 bound to the Gemin2-binding domain of SMN determined by NMR spectroscopy. This complex reveals the structure of Gemin2, how Gemin2 binds to SMN and the roles of conserved SMN residues near the binding interface. Surprisingly, several conserved SMN residues, including the sites of two SMA patient mutations, are not required for binding to Gemin2. Instead, they form a conserved SMN/Gemin2 surface that may be functionally important for snRNP assembly. The SMN–Gemin2 structure explains how Gemin2 is stabilized by SMN and establishes a framework for structure–function studies to investigate snRNP biogenesis as well as biological processes involving Gemin2 that do not involve snRNP assembly. PMID:22607171

Sarachan, Kathryn L.; Valentine, Kathleen G.; Gupta, Kushol; Moorman, Veronica R.; Gledhill, John M.; Bernens, Matthew; Tommos, Cecilia; Wand, A. Joshua; Van Duyne, Gregory D.

2012-01-01

203

Macromolecular networks and intelligence in microorganisms  

PubMed Central

Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of information and communication technology (ICT): they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity – particularly activity of the human brain – with a phenomenon we call “intelligence.” Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as “human” and “brain” out of the defining features of “intelligence,” all forms of life – from microbes to humans – exhibit some or all characteristics consistent with “intelligence.” We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo. PMID:25101076

Westerhoff, Hans V.; Brooks, Aaron N.; Simeonidis, Evangelos; García-Contreras, Rodolfo; He, Fei; Boogerd, Fred C.; Jackson, Victoria J.; Goncharuk, Valeri; Kolodkin, Alexey

2014-01-01

204

Discrimination of solvent from protein regions in native Fouriers as a means of evaluating heavy-atom solutions in the MIR and MAD methods  

PubMed Central

An automated examination of the native Fourier is tested as a means of evaluation of a heavy-atom solution in MAD and MIR methods for macromolecular crystallography. It is found that the presence of distinct regions of high and low density variation in electron-density maps is a good indicator of the correctness of a heavy-atom solution in the MIR and MAD methods. The method can be used to evaluate heavy-atom solutions during MAD and MIR structure solutions and to determine the handedness of the structure if anomalous data have been measured. PMID:10089362

Terwilliger, Thomas C.; Berendzen, Joel

1999-01-01

205

Discrimination of solvent from protein regions in native Fouriers as a means of evaluating heavy-atom solutions in the MIR and MAD methods.  

PubMed

An automated examination of the native Fourier is tested as a means of evaluation of a heavy-atom solution in MAD and MIR methods for macromolecular crystallography. It is found that the presence of distinct regions of high and low density variation in electron-density maps is a good indicator of the correctness of a heavy-atom solution in the MIR and MAD methods. The method can be used to evaluate heavy-atom solutions during MAD and MIR structure solutions and to determine the handedness of the structure if anomalous data have been measured. PMID:10089362

Terwilliger, T C; Berendzen, J

1999-02-01

206

Structure and dynamics of aqueous solution of uranyl ions  

SciTech Connect

The present work describes a molecular dynamics simulation study of structure and dynamics of aqueous solution of uranyl ions in water. Structural properties of the system in terms of radial distribution functions and dynamical characteristics as obtained through velocity autocorrelation function and mean square displacements have been analyzed. The results for radial distribution functions show the oxygen of water to form the first solvation shell at 2.4 Å around the uranium atom, whereas the hydrogen atoms of water are distributed around the uranium atom with the major peak at around 3.0 Å. Analyses of transport behaviors of ions and water through MSD indicates that the diffusion of the uranyl ion is much less as compared to that of the water molecules. It is also observed that the dynamical behavior of water molecules gets modified due to the presence of uranyl ion. The effect of increase in concentration of uranyl ions on the structure and dynamics of water molecules is also studied.

Chopra, Manish [Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai-400085 (India); Choudhury, Niharendu, E-mail: nihcho@barc.gov.in [Theoretical Chemistry Section, Bhabha Atomic Research Centre, Mumbai-400085 (India)

2014-04-24

207

Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior  

E-print Network

Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding ...

Zeiger, Adam Scott

208

JBluIce–EPICS control system for macromolecular crystallography  

PubMed Central

The trio of macromolecular crystallography beamlines constructed by the General Medicine and Cancer Institutes Collaborative Access Team (GM/CA-CAT) in Sector 23 of the Advanced Photon Source (APS) have been in growing demand owing to their outstanding beam quality and capacity to measure data from crystals of only a few micrometres in size. To take full advantage of the state-of-the-art mechanical and optical design of these beamlines, a significant effort has been devoted to designing fast, convenient, intuitive and robust beamline controls that could easily accommodate new beamline developments. The GM/CA-CAT beamline controls are based on the power of EPICS for distributed hardware control, the rich Java graphical user interface of Eclipse RCP and the task-oriented philosophy as well as the look and feel of the successful SSRL BluIce graphical user interface for crystallography. These beamline controls feature a minimum number of software layers, the wide use of plug-ins that can be written in any language and unified motion controls that allow on-the-fly scanning and optimization of any beamline com­ponent. This paper describes the ways in which BluIce was combined with EPICS and converted into the Java-based JBluIce, discusses the solutions aimed at streamlining and speeding up operations and gives an overview of the tools that are provided by this new open-source control system for facilitating crystallo­graphic experiments, especially in the field of microcrystallo­graphy. PMID:21358048

Stepanov, Sergey; Makarov, Oleg; Hilgart, Mark; Pothineni, Sudhir Babu; Urakhchin, Alex; Devarapalli, Satish; Yoder, Derek; Becker, Michael; Ogata, Craig; Sanishvili, Ruslan; Venugopalan, Nagarajan; Smith, Janet L.; Fischetti, Robert F.

2011-01-01

209

Solution-processable graphene nanomeshes with controlled pore structures  

NASA Astrophysics Data System (ADS)

Graphene nanomeshes (GNMs) which can be cheaply produced on a large scale and processed through wet approaches are important materials for various applications, including catalysis, composites, sensors and energy related systems. Here, we report a method for large scale preparation of GNMs by refluxing reduced graphene oxide sheets in concentrated nitric acid solution (e.g., 8 moles per liter). The diameters of nanopores in GNM sheets can be readily modulated from several to hundreds nanometers by varying the time of acid treatment. The porous structure increased the specific surface areas of GNMs and the transmittances of GNM-based thin films. Furthermore, GNMs have large number of carboxyl groups at the edges of their nanopores, leading to good dispersibility in aqueous media and strong peroxidase-like catalytic activity.

Wang, Xiluan; Jiao, Liying; Sheng, Kaixuan; Li, Chun; Dai, Liming; Shi, Gaoquan

2013-06-01

210

The solution structure of the copper clioquinol complex.  

PubMed

Clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) recently has shown promising results in the treatment of Alzheimer's disease and in cancer therapy, both of which also are thought to be due to clioquinol's ability as a lipophilic copper chelator. Previously, clioquinol was used as an anti-fungal and anti-protozoal drug that was responsible for an epidemic of subacute myelo-optic neuropathy (SMON) in Japan during the 1960s, probably a myeloneuropathy arising from a clioquinol-induced copper deficiency. Previous X-ray absorption spectroscopy of solutions of copper chelates of clioquinol suggested unusual coordination chemistry. Here we use a combination of electron paramagnetic, UV-visible and X-ray absorption spectroscopies to provide clarification of the chelation chemistry between clioquinol and copper. We find that the solution structures for the copper complexes formed with stoichiometric and excess clioquinol are conventional 8-hydroxyquinolate chelates. Thus, the promise of clioquinol in new treatments for Alzheimer's disease and in cancer therapy is not likely to be due to any novel chelation chemistry, but rather due to other factors including the high lipophilicity of the free ligand and chelate complexes. PMID:24503514

Pushie, M Jake; Nienaber, Kurt H; Summers, Kelly L; Cotelesage, Julien J H; Ponomarenko, Olena; Nichol, Helen K; Pickering, Ingrid J; George, Graham N

2014-04-01

211

Characterization of Chitin and Chitosan Molecular Structure in Aqueous Solution  

SciTech Connect

Molecular dynamics simulations have been used to characterize the structure of chitin and chitosan fibers in aqueous solutions. Chitin fibers, whether isolated or in the form of a ?-chitin nanoparticle, adopt the so-called 2-fold helix with ? and ? values similar to its crystalline state. In solution, the intramolecular hydrogen bond HO3(n)?O5(n+1) responsible for the 2-fold helical motif is stabilized by hydrogen bonds with water molecules in a well-defined orientation. On the other hand, chitosan can adopt five distinct helical motifs and its conformational equilibrium is highly dependent on pH. The hydrogen bond pattern and solvation around the O3 atom of insoluble chitosan (basic pH) are nearly identical to these quantities in chitin. Our findings suggest that the solubility and conformation of these polysaccharides are related to the stability of the intrachain HO3(n)?O5(n+1) hydrogen bond, which is affect by the water exchange around the O3-HO3 hydroxyl group.

Franca, Eduardo D.; Lins, Roberto D.; Freitas, Luiz C.; Straatsma, TP

2008-12-01

212

Identifying duplicate crystal structures: XTALCOMP, an open-source solution  

NASA Astrophysics Data System (ADS)

We describe the implementation of XTALCOMP, an efficient, reliable, and open-source library that tests if two crystal descriptions describe the same underlying structure. The algorithm has been tested and found to correctly identify duplicate structures in spite of the "real-world" difficulties that arise from working with numeric crystal representations: degenerate unit cell lattices, numerical noise, periodic boundaries, and the lack of a canonical coordinate origin. The library is portable, open, and not dependent on any external packages. A web interface to the algorithm is publicly accessible at http://xtalopt.openmolecules.net/xtalcomp/xtalcomp.html. Program summaryProgram title: XtalComp Catalogue identifier: AEKV_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKV_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: "New" (3-clause) BSD [1] No. of lines in distributed program, including test data, etc.: 3148 No. of bytes in distributed program, including test data, etc.: 21 860 Distribution format: tar.gz Programming language: C++ Computer: No restrictions Operating system: All operating systems with a compliant C++ compiler. Classification: 7.8 Nature of problem: Computationally identifying duplicate crystal structures taken from the output of modern solid state calculations is a non-trivial exercise for many reasons. The translation vectors in the description are not unique — they may be transformed into linear combinations of themselves and continue to describe the same extended structure. The coordinates and cell parameters contain numerical noise. The periodic boundary conditions at the unit cell faces, edges, and corners can cause very small displacements of atomic coordinates to result in very different representations. The positions of all atoms may be uniformly translated by an arbitrary vector without modifying the underlying structure. Additionally, certain applications may consider enantiomorphic structures to be identical. Solution method: The XtalComp algorithm overcomes these issues to detect duplicate structures regardless of differences in representation. It begins by performing a Niggli reduction on the inputs, standardizing the translation vectors and orientations. A transform search is performed to identify candidate sets of rotations, reflections, and translations that potentially map the description of one crystal onto the other, solving the problems of enantiomorphs and rotationally degenerate lattices. The atomic positions resulting from each candidate transform are then compared, using a cell-expansion technique to remove periodic boundary issues. Computational noise is treated by comparing non-integer quantities using a specified tolerance. Running time: The test run provided takes less than a second to complete.

Lonie, David C.; Zurek, Eva

2012-03-01

213

Macromolecular crystallography beamline X25 at the NSLS  

PubMed Central

Beamline X25 at the NSLS is one of the five beamlines dedicated to macromolecular crystallography operated by the Brookhaven National Laboratory Macromolecular Crystallography Research Resource group. This mini-gap insertion-device beamline has seen constant upgrades for the last seven years in order to achieve mini-beam capability down to 20?µm × 20?µm. All major components beginning with the radiation source, and continuing along the beamline and its experimental hutch, have changed to produce a state-of-the-art facility for the scientific community. PMID:24763654

Héroux, Annie; Allaire, Marc; Buono, Richard; Cowan, Matthew L.; Dvorak, Joseph; Flaks, Leon; LaMarra, Steven; Myers, Stuart F.; Orville, Allen M.; Robinson, Howard H.; Roessler, Christian G.; Schneider, Dieter K.; Shea-McCarthy, Grace; Skinner, John M.; Skinner, Michael; Soares, Alexei S.; Sweet, Robert M.; Berman, Lonny E.

2014-01-01

214

Phase sensitive x-ray diffraction imaging of defects in biological macromolecular crystals  

NASA Technical Reports Server (NTRS)

Conventional x-ray diffraction topography is currently used to map defects in the bulk of protein crystals, but the lack of sufficient contrast is frequently a limiting factor. We experimentally demonstrate that this barrier can be circumvented using a method that combines phase sensitive and diffraction imaging principles. Details of defects revealed in tetragonal lysozyme and cubic ferritin crystals are presented and discussed. The approach enabling the detection of the phase changes of diffracted x rays should prove to be useful in the study of defect structures in a broad range of biological macromolecular crystals.

Hu, Z. W.; Lai, B.; Chu, Y. S.; Cai, Z.; Mancini, D. C.; Thomas, B. R.; Chernov, A. A.

2001-01-01

215

Analytical solution of thermal magnetization on memory stabilizer structures  

SciTech Connect

We return to the question of how the choice of stabilizer generators affects the preservation of information on structures whose degenerate ground state encodes a classical redundancy code. Controlled-not gates are used to transform the stabilizer Hamiltonian into a Hamiltonian consisting of uncoupled single spins and/or pairs of spins. This transformation allows us to obtain an analytical partition function and derive closed-form equations for the relative magnetization and susceptibility. These equations are in agreement with the numerical results presented in Viteri et al. [Phys. Rev. A 80, 042313 (2009)] for finite size systems. Analytical solutions show that there is no finite critical temperature, T{sub c}=0, for all of the memory structures in the thermodynamic limit. This is in contrast to the previously predicted finite critical temperatures based on extrapolation. The mismatch is a result of the infinite system being a poor approximation even for astronomically large finite-size systems, where spontaneous magnetization still arises below an apparent finite critical temperature. We extend our analysis to the canonical stabilizer Hamiltonian. Interestingly, Hamiltonians with two-body interactions have a higher apparent critical temperature than the many-body Hamiltonian.

Tomita, Yu; Viteri, C. Ricardo; Brown, Kenneth R. [Schools of Chemistry and Biochemistry, Computational Science and Engineering, and Physics, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States)

2010-10-15

216

The nanoheterogeneous structure of aqueous solutions of n-propanol  

NASA Astrophysics Data System (ADS)

The results of positron spectroscopy and molecular light scattering studies, the data on radiationchemical yields and optical absorption spectra of solvated electrons formed under the action of ionizing radiation, and the data on the concentration dependences of viscosity, adiabatic compressibility, the velocity of sound, and partial molar volume were used to determine the structure of water- n-propanol mixtures. The conclusion was drawn that the insertion of alcohol molecules into water network voids over the range of alcohol mole fractions 0 < x 2 < 0.05 strengthened the structure of water. A further increase in the concentration of the alcohol caused the destruction of the aqueous component and solution homogenization. At 0.01 < x 2 < 0.3, mixtures resembled an emulsion of alcohol “nanodrops” suspended in water. At 0.3 < x 2 < 0.9, the system again became homogeneous. Lastly, when water was added to pure n-propanol (1 > x 2 > 0.9), its molecules combined into nanodrops.

Byakov, V. M.; Lanshina, L. V.; Stepanova, O. P.; Stepanov, S. V.

2009-02-01

217

A Compact X-Ray System for Macromolecular Crystallography  

NASA Technical Reports Server (NTRS)

We describe the design and performance of a high flux x-ray system for a macromolecular crystallography that combines a microfocus x-ray generator (40 micrometer full width at half maximum spot size at a power level of 46.5 W) and a collimating polycapillary optic. The Cu Ka lpha x-ray flux produced by this optimized system through a 500,um diam orifice is 7.0 times greater than the x-ray flux previously reported by Gubarev et al. [M. Gubarev et al., J. Appl. Crystallogr. 33, 882 (2000)]. The x-ray flux from the microfocus system is also 2.6 times higher than that produced by a rotating anode generator equipped with a graded multilayer monochromator (green optic, Osmic Inc. CMF24-48-Cu6) and 40% less than that produced by a rotating anode generator with the newest design of graded multilayer monochromator (blue optic, Osmic, Inc. CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 W, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42 540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym)=5.0% for data extending to 1.70 A, and 4.8% for the complete set of data to 1.85 A. The amplitudes of the observed reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Gibson, Walter; Joy, Marshall

2000-01-01

218

A Compact X-Ray System for Macromolecular Crystallography. 5  

NASA Technical Reports Server (NTRS)

We describe the design and performance of a high flux x-ray system for macromolecular crystallography that combines a microfocus x-ray generator (40 gm FWHM spot size at a power level of 46.5Watts) and a 5.5 mm focal distance polycapillary optic. The Cu K(sub alpha) X-ray flux produced by this optimized system is 7.0 times above the X-ray flux previously reported. The X-ray flux from the microfocus system is also 3.2 times higher than that produced by the rotating anode generator equipped with a long focal distance graded multilayer monochromator (Green optic; CMF24-48-Cu6) and 30% less than that produced by the rotating anode generator with the newest design of graded multilayer monochromator (Blue optic; CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 Watts, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42,540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym) 5.0% for the data extending to 1.7A, and 4.8% for the complete set of data to 1.85A. The amplitudes of the reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Joy, Marshall

2000-01-01

219

Facilities for macromolecular crystallography at the Helmholtz-Zentrum Berlin.  

PubMed

Three macromolecular crystallography (MX) beamlines at the Helmholtz-Zentrum Berlin (HZB) are available for the regional, national and international structural biology user community. The state-of-the-art synchrotron beamlines for MX BL14.1, BL14.2 and BL14.3 are located within the low-? section of the BESSY II electron storage ring. All beamlines are fed from a superconducting 7?T wavelength-shifter insertion device. BL14.1 and BL14.2 are energy tunable in the range 5-16?keV, while BL14.3 is a fixed-energy side station operated at 13.8?keV. All three beamlines are equipped with CCD detectors. BL14.1 and BL14.2 are in regular user operation providing about 200 beam days per year and about 600?user shifts to approximately 50 research groups across Europe. BL14.3 has initially been used as a test facility and was brought into regular user mode operation during the year 2010. BL14.1 has recently been upgraded with a microdiffractometer including a mini-? goniometer and an automated sample changer. Additional user facilities include office space adjacent to the beamlines, a sample preparation laboratory, a biology laboratory (safety level 1) and high-end computing resources. In this article the instrumentation of the beamlines is described, and a summary of the experimental possibilities of the beamlines and the provided ancillary equipment for the user community is given. PMID:22514183

Mueller, Uwe; Darowski, Nora; Fuchs, Martin R; Förster, Ronald; Hellmig, Michael; Paithankar, Karthik S; Pühringer, Sandra; Steffien, Michael; Zocher, Georg; Weiss, Manfred S

2012-05-01

220

Macromolecules in drug delivery Macromolecular targeting agents, carriers, and drugs  

E-print Network

Macromolecules in drug delivery Macromolecular targeting agents, carriers, and drugs 1gauthier@emt.inrs.ca #12;Why macromolecules in drug delivery? 2gauthier@emt.inrs.ca Classic chemotherapy Drug delivery? Targeting A carrier for small drugs A release mechanism (if necessary) Protection of drug cargo #12;How? 3

Barthelat, Francois

221

Macromolecular Transport across Arterial and Venous Endothelium in Rats  

E-print Network

Macromolecular Transport across Arterial and Venous Endothelium in Rats Studies with Evans Blue- cence microscopic examination of en face preparation of the aorta stained with hematoxylln allowed to the "blue areas" for EBA or "brown areas" for HRP. Compared wtth arteries, veins had fewer mltotlc cells

Chuang, Pao-Tien

222

Ground Based Program for the Physical Analysis of Macromolecular Crystal Growth  

NASA Technical Reports Server (NTRS)

During the past year we have focused on application of in situ Atomic Force Microscopy (AFM) for studies of the growth mechanisms and kinetics of crystallization for different macromolecular systems. Mechanisms of macrostep formation and their decay, which are important in understanding of defect formation, were studied on the surfaces of thaumatin, catalase, canavalin and lysozyme crystals. Experiments revealed that step bunching on crystalline surfaces occurred either due to two- or three-dimensional nucleation on the terraces of vicinal slopes or as a result of uneven step generation by complex dislocation sources. No step bunching arising from interaction of individual steps in the course of the experiment was observed. The molecular structure of the growth steps for thaumatin and lipase crystals were deduced. It was further shown that growth step advance occurs by incorporation of single protein molecules. In singular directions growth steps move by one-dimensional nucleation on step edges followed by lateral growth. One-dimensional nuclei have different sizes, less then a single unit cell, varying for different directions of step movement. There is no roughness due to thermal fluctuations, and each protein molecule which incorporated into the step remained. Growth kinetics for catalase crystals was investigated over wide supersaturation ranges. Strong directional kinetic anisotropy in the tangential step growth rates in different directions was seen. The influence of impurities on growth kinetics and cessation of macromolecular crystals was studied. Thus, for catalase, in addition to pronounced impurity effects on the kinetics of crystallization, we were also able to directly observe adsorption of some impurities. At low supersaturation we repeatedly observed filaments which formed from impurity molecules sedimenting on the surfaces. Similar filaments were observed on the surfaces of thaumatin, canavalin and STMV crystals as well, but the frequency was low compared with catalase crystallization. Cessation of growth of xylanase and lysozyme crystals was also observed and appeared to be a consequence of the formation of dense impurity adsorption layers. Attachment: "An in situ AFM investigation of catalase crystallization", "Atomic force microscopy studies of living cells: visualization of motility, division, aggregation, transformation, and apoptosis", AFM studies on mechanisms of nucleation and growth of macromolecular crystals", and "In situ atomic force microscopy studies of surface morphology, growth kinetics, defect structure and dissolution in macromolecular crystallization".

Malkin, Alexander J.

1998-01-01

223

a Procedural Solution to Model Roman Masonry Structures  

NASA Astrophysics Data System (ADS)

The paper will describe a new approach based on the development of a procedural modelling methodology for archaeological data representation. This is a custom-designed solution based on the recognition of the rules belonging to the construction methods used in roman times. We have conceived a tool for 3D reconstruction of masonry structures starting from photogrammetric surveying. Our protocol considers different steps. Firstly we have focused on the classification of opus based on the basic interconnections that can lead to a descriptive system used for their unequivocal identification and design. Secondly, we have chosen an automatic, accurate, flexible and open-source photogrammetric pipeline named Pastis Apero Micmac - PAM, developed by IGN (Paris). We have employed it to generate ortho-images from non-oriented images, using a user-friendly interface implemented by CNRS Marseille (France). Thirdly, the masonry elements are created in parametric and interactive way, and finally they are adapted to the photogrammetric data. The presented application, currently under construction, is developed with an open source programming language called Processing, useful for visual, animated or static, 2D or 3D, interactive creations. Using this computer language, a Java environment has been developed. Therefore, even if the procedural modelling reveals an accuracy level inferior to the one obtained by manual modelling (brick by brick), this method can be useful when taking into account the static evaluation on buildings (requiring quantitative aspects) and metric measures for restoration purposes.

Cappellini, V.; Saleri, R.; Stefani, C.; Nony, N.; De Luca, L.

2013-07-01

224

Structure Formation in Semi-Dilute Polymer Solution during Electrospinning  

NASA Astrophysics Data System (ADS)

In our recent work it was shown that longitudinal stretching of electrospun highly entangled semi-dilute polymer solution caused by jet hydrodynamic forces, transforms the topological network to an almost fully-stretched state within less than 1 mm from the jet start (PRE, 2011). Further evolution of the polymer network is related to a disentanglement of polymer chains and transformation of the topological network structure. As was sown by Malkin et al., (Rheol. Acta, 2011) high deformation rate of a topological polymer network, results in reptations of macromolecules caused by uncompensated local forces, whereas Brownian motion effect is negligible. Based on this conclusion, we examine the disentanglement process, using a mechanical pulley-block system assembled from multiple pulleys suspended by elastic springs, and taut string connecting two blocks. Each pulley corresponds to a topological knot; the taut string corresponds to a reptated chain; the springs correspond to surrounded polymer chains; and the blocks correspond to local deformation force. It turned out that the system is sensitive to system parameters. The pulleys can approach each other and the string stops to move. Such a behavior corresponds to formation of bundle of knots of entangled chains. In other conditions, the string continuously moves while the pulleys did not approach each other which corresponds to disentanglement of polymer chains. These experiments clarify the disentanglement kinetics in rapid-deformed polymer system.

Zussman, Eyal; Paley, Yakov; Arinstein, Arkadii; Shuster, Kim

2012-02-01

225

Localization of Protein Aggregation in Escherichia coli Is Governed by Diffusion and Nucleoid Macromolecular Crowding Effect  

PubMed Central

Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli) where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian). Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results provide evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3D individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids) are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion-aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of “soft” intracellular structuring (based on macromolecular crowding) in diffusion-based protein localization in E. coli. PMID:23633942

Coquel, Anne-Sophie; Jacob, Jean-Pascal; Primet, Mael; Demarez, Alice; Dimiccoli, Mariella; Julou, Thomas; Moisan, Lionel

2013-01-01

226

Structure, singular points and existence of multiple solutions in load flow analysis  

SciTech Connect

Since the load-flow equations are nonlinear, they have multiple solutions. The multiple solution problem is important for an ill-conditioned system and also for voltage instability phenomena. The load flow equations in quadratic form to clarify the structure of multiple solutions are presented. Also, a heuristic method to find multiple solutions is proposed and a discussion of the properties of very close solutions is presented.

Nakanishi, Y.; Yamada, K.; Nagasawa, H.; Iwamoto, S.; Tamura, Y.

1980-05-01

227

Characterization of the Effects of Nonspecific Xenon–Protein Interactions on 129Xe Chemical Shifts in Aqueous Solution: Further Development of Xenon as a Biomolecular Probe  

Microsoft Academic Search

The sensitivity of 129Xe chemical shifts to weak nonspecific xenon–protein interactions has suggested the use of xenon to probe biomolecular structure and interactions. The realization of this potential necessitates a further understanding of how different macromolecular properties influence the 129Xe chemical shift in aqueous solution. Toward this goal, we have acquired 129Xe NMR spectra of xenon dissolved in amino acid,

Seth M. Rubin; Megan M. Spence; Alexander Pines; David E. Wemmer

2001-01-01

228

NMR Structure Improvement: A Structural Bioinformatics & Visualization Approach. Jeremy N. Block  

E-print Network

of macromolecular structure and its dynamic variation enhances the effectiveness of the many biomedical applications demonstrating that hurtful stereotypes and misconceptions can be overcome. #12;vi Contents Abstract

Richardson, David

229

SASSIE: A program to study intrinsically disordered biological molecules and macromolecular ensembles using experimental scattering restraints  

NASA Astrophysics Data System (ADS)

A program to construct ensembles of biomolecular structures that are consistent with experimental scattering data are described. Specifically, we generate an ensemble of biomolecular structures by varying sets of backbone dihedral angles that are then filtered using experimentally determined restraints to rapidly determine structures that have scattering profiles that are consistent with scattering data. We discuss an application of these tools to predict a set of structures for the HIV-1 Gag protein, an intrinsically disordered protein, that are consistent with small-angle neutron scattering experimental data. We have assembled these algorithms into a program called SASSIE for structure generation, visualization, and analysis of intrinsically disordered proteins and other macromolecular ensembles using neutron and X-ray scattering restraints. Program summaryProgram title: SASSIE Catalogue identifier: AEKL_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKL_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License v3 No. of lines in distributed program, including test data, etc.: 3 991 624 No. of bytes in distributed program, including test data, etc.: 826 Distribution format: tar.gz Programming language: Python, C/C++, Fortran Computer: PC/Mac Operating system: 32- and 64-bit Linux (Ubuntu 10.04, Centos 5.6) and Mac OS X (10.6.6) RAM: 1 GB Classification: 3 External routines: Python 2.6.5, numpy 1.4.0, swig 1.3.40, scipy 0.8.0, Gnuplot-py-1.8, Tcl 8.5, Tk 8.5, Mac installation requires aquaterm 1.0 (or X window system) and Xcode 3 development tools. Nature of problem: Open source software to generate structures of disordered biological molecules that subsequently allow for the comparison of computational and experimental results is limiting the use of scattering resources. Solution method: Starting with an all atom model of a protein, for example, users can input regions to vary dihedral angles, ensembles of structures can be generated. Additionally, simple two-body rigid-body rotations are supported with and without disordered regions. Generated structures can then be used to calculate small-angle scattering profiles which can then be filtered against experimentally determined data. Filtered structures can be visualized individually or as an ensemble using density plots. In the modular and expandable program framework the user can easily access our subroutines and structural coordinates can be easily obtained for study using other computational physics methods. Additional comments: The distribution file for this program is over 159 Mbytes and therefore is not delivered directly when download or Email is requested. Instead an html file giving details of how the program can be obtained is sent. Running time: Varies depending on application. Typically 10 minutes to 24 hours depending on the number of generated structures.

Curtis, Joseph E.; Raghunandan, Sindhu; Nanda, Hirsh; Krueger, Susan

2012-02-01

230

A brief history of macromolecular crystallography, illustrated by a family tree and its Nobel fruits.  

PubMed

As a contribution to the celebration of the year 2014, declared by the United Nations to be 'The International Year of Crystallography', the FEBS Journal is dedicating this issue to papers showcasing the intimate union between macromolecular crystallography and structural biology, both in historical perspective and in current research. Instead of a formal editorial piece, by way of introduction, this review discusses the most important, often iconic, achievements of crystallographers that led to major advances in our understanding of the structure and function of biological macromolecules. We identified at least 42 scientists who received Nobel Prizes in Physics, Chemistry or Medicine for their contributions that included the use of X-rays or neutrons and crystallography, including 24 who made seminal discoveries in macromolecular sciences. Our spotlight is mostly, but not only, on the recipients of this most prestigious scientific honor, presented in approximately chronological order. As a summary of the review, we attempt to construct a genealogy tree of the principal lineages of protein crystallography, leading from the founding members to the present generation. PMID:24698025

Jaskolski, Mariusz; Dauter, Zbigniew; Wlodawer, Alexander

2014-09-01

231

Solutions  

NASA Astrophysics Data System (ADS)

Type-VIII Ba8Ga16Sn30 polycrystalline clathrates were grown vertically downwards from Ba8Ga16Sn50 solution at furnace temperatures between 500°C and 800°C with an ampoule velocity of 0.36 cm/h. The microstructure, composition, crystal structure, and thermoelectric properties of crystals were investigated. Polycrystalline samples in which Ba8Ga16Sn30 grains were wetted by an Sn-rich phase were prepared. In general, grain size increases along the direction of growth. It was found that the sample grown at 650°C had the largest grains. Smaller grains were observed for samples grown at lower temperatures, as a result of higher rate of nucleation, because of higher undercooling at the solid-liquid interface caused by the lower thermal gradient in the liquid. However, at furnace temperatures higher than 650°C enhanced convection in the solution at higher temperature gradients and wetting phenomena may cause instability of the solid-liquid interface and solid nuclei may flow into the liquid to become new nucleation sites. This explains the decrease of grain size at higher furnace temperatures. The optimum ZT and power factor of the undoped Ba8Ga16Sn30 clathrate prepared by the vertical Bridgman method in this study were, respectively, 0.8 and 11.4 ?W/cmK2 at 200°C; the Seebeck coefficient was -260 ?V/K.

Hong, Qin-Gang; Chang, Li-Shin; Hsieh, Huey-Lin

2014-06-01

232

Evidence for water structuring forces between surfaces  

SciTech Connect

Structured water on apposing surfaces can generate significant energies due to reorganization and displacement as the surfaces encounter each other. Force measurements on a multitude of biological structures using the osmotic stress technique have elucidated commonalities that point toward an underlying hydration force. In this review, the forces of two contrasting systems are considered in detail: highly charged DNA and nonpolar, uncharged hydroxypropyl cellulose. Conditions for both net repulsion and attraction, along with the measured exclusion of chemically different solutes from these macromolecular surfaces, are explored and demonstrate features consistent with a hydration force origin. Specifically, the observed interaction forces can be reduced to the effects of perturbing structured surface water.

Stanley, Christopher B [ORNL; Rau, Dr. Donald [National Institutes of Health

2011-01-01

233

Gelation of aqueous gelatin solutions. I. Structural investigation Madeleine Djabourov, Jacques Leblond and Pierre Papon  

E-print Network

319 Gelation of aqueous gelatin solutions. I. Structural investigation Madeleine Djabourov, Jacques modifications of aqueous gelatin solutions for various thermal treatments and different concentrations Physics Abstracts 82.70 - 07.60F - 61.40 The gelation of aqueous gelatin solutions is a process which has

Paris-Sud XI, Université de

234

Solution structure of synthetic penaeidin-4 with structural and functional comparisons with penaeidin-3.  

PubMed

Antimicrobial peptide structure has direct implications for the complexity of functions and mechanisms of action. The penaeidin antimicrobial peptide family from shrimp is divided into multiple class designations based on primary structure. The penaeidin classes are not only characterized by variability in primary sequence but also by variation in target specificity and effectiveness. Whereas class 4 exhibits low isoform diversity within species and is highly conserved between species, the primary sequence of penaeidin class 3 is less conserved between species and exhibits considerable isoform diversity within species. All penaeidins, regardless of class or species, are composed of two dramatically different domains: an unconstrained proline-rich domain and a disulfide bond-stabilized cysteine-rich domain. The proline-rich domain varies in length and is generally less conserved, whereas the spacing and specific residue content of the cysteine-rich domain is more conserved. The structure of the synthetic penaeidin class 4 (PEN4-1) from Litopenaeus setiferus was analyzed using several approaches, including chemical mapping of disulfide bonds, circular dichroism analysis of secondary structural characteristics, and complete characterization of the solution structure of the peptide by proton NMR. L. setiferus PEN4-1 was then compared with the previously characterized structure of penaeidin class 3 from Litopenaeus vannamei. Moreover, the specificity of these antimicrobial peptides was examined through direct comparison of activity against a panel of microbes. The penaeidin classes differ in microbial target specificity, which correlates to variability in specific domain sequence. However, the tertiary structure of the cysteine-rich domain and indeed the overall structure of penaeidins are conserved across classes. PMID:15699044

Cuthbertson, Brandon J; Yang, Yinshan; Bachère, Evelyne; Büllesbach, Erika E; Gross, Paul S; Aumelas, André

2005-04-22

235

Application of finite-element-based solution technologies for viscoplastic structural analyses  

NASA Technical Reports Server (NTRS)

Finite-element solution technology developed for use in conjunction with advanced viscoplastic models is described. The development of such solution technology is necessary for performing stress/life analyses of engineering structural problems where the complex geometries and loadings make the conventional analytical solutions difficult. The versatility of the solution technology is demonstrated by applying it to viscoplastic models possessing different mathematical structures and encompassing isotropic and anisotropic materials. The computational results qualitatively replicate deformation behavior observed in experiments on prototypical structural components.

Arya, Vinod K.

1991-01-01

236

Application of finite-element-based solution technologies for viscoplastic structural analyses  

NASA Technical Reports Server (NTRS)

Finite-element solution technology developed for use in conjunction with advanced viscoplastic models is described. The development of such solution technology is necessary for performing stress/life analyses of engineering structural problems where the complex geometries and loadings make the conventional analytical solutions difficult. The versatility of the solution technology is demonstrated by applying it to viscoplastic models possessing different mathematical structures and encompassing isotropic and anisotropic material. The computational results qualitatively replicate deformation behavior observed in experiments on prototypical structural components.

Arya, V. K.

1990-01-01

237

Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex  

PubMed Central

Pathogen recognition by nucleotide-binding oligomerization domain-like receptor (NLR) results in the formation of a macromolecular protein complex (inflammasome) that drives protective inflammatory responses in the host. It is thought that the number of inflammasome complexes forming in a cell is determined by the number of NLRs being activated, with each NLR initiating its own inflammasome assembly independent of one another; however, we show here that the important foodborne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) simultaneously activates at least two NLRs, whereas only a single inflammasome complex is formed in a macrophage. Both nucleotide-binding domain and leucine-rich repeat caspase recruitment domain 4 and nucleotide-binding domain and leucine-rich repeat pyrin domain 3 are simultaneously present in the same inflammasome, where both NLRs are required to drive IL-1? processing within the Salmonella-infected cell and to regulate the bacterial burden in mice. Superresolution imaging of Salmonella-infected macrophages revealed a macromolecular complex with an outer ring of apoptosis-associated speck-like protein containing a caspase activation and recruitment domain and an inner ring of NLRs, with active caspase effectors containing the pro–IL-1? substrate localized internal to the ring structure. Our data reveal the spatial localization of different components of the inflammasome and how different members of the NLR family cooperate to drive robust IL-1? processing during Salmonella infection. PMID:24803432

Man, Si Ming; Hopkins, Lee J.; Nugent, Eileen; Cox, Susan; Glück, Ivo M.; Tourlomousis, Panagiotis; Wright, John A.; Cicuta, Pietro; Monie, Tom P.; Bryant, Clare E.

2014-01-01

238

Structural and dynamic heterogeneity in a telechelic polymer solution Dmitry Bedrova,*, Grant Smitha  

E-print Network

Structural and dynamic heterogeneity in a telechelic polymer solution Dmitry Bedrova,*, Grant dynamics in a model telechelic polymer solution. The transient structural heterogeneity associated South Central Campus Drive, Room 304, Salt Lake City, UT 84112-0560, USA b Polymers Division, National

Utah, University of

239

Localization of bound water in the solution structure of a complex of the erythroid  

E-print Network

words: bound water, GATA-1-DNA complex, NMR solution structure, protein hydration Introduction A numberLocalization of bound water in the solution structure of a complex of the erythroid transcription as a monomer to the asymmetric consensus target sequence (T/A)GATA- (A/G) found in the cis-regulatory elements

Clore, G. Marius

240

New Insights into Histidine Triad Proteins: Solution Structure of a Streptococcus pneumoniae PhtD Domain  

E-print Network

New Insights into Histidine Triad Proteins: Solution Structure of a Streptococcus pneumoniae Pht membranes of Streptococcus pneumoniae (S. pneumoniae) demonstrate that native PhtD and AdcAII interact into Histidine Triad Proteins: Solution Structure of a Streptococcus pneumoniae PhtD Domain and Zinc Transfer

Paris-Sud XI, Université de

241

On the variability of experimental data in macromolecular crystallography  

PubMed Central

Experimental errors as determined by data-processing algorithms in macromolecular crystallography are compared with the direct error estimates obtained by a multiple crystal data-collection protocol. It is found that several-fold error inflation is necessary to account for crystal-to-crystal variation. It is shown that similar error inflation is observed for data collected from multiple sections of the same crystal, indicating non-uniform crystal growth as one of the likely sources of additional data variation. Other potential sources of error inflation include differential X-ray absorption for different reflections and variation of unit-cell parameters. The underestimation of the experimental errors is more severe in lower resolution shells and for reflections characterized by a higher signal-to-noise ratio. These observations partially account for the gap between the expected and the observed R values in macromolecular crystallography. PMID:22948908

Pozharski, Edwin

2012-01-01

242

Solution X-ray scattering as a probe of hydration-dependent structuring of aqueous solutions  

Microsoft Academic Search

We report on new X-ray solution scattering experiments and molecular dynamics simulations conducted for increasing solute concentrations of N-acetyl-amino acid-amides and -methylamides in water, for the amino acids leucine, glutamine, and glycine. As the concentration increases, the main diffraction peak of pure water at Q = 2.0 Å-1 shifts to smaller angle for the larger leucine and glutamine amino acids,

Greg Hura; Jon M. Sorenson; Robert M. Glaeser; Teresa Head-Gordon

1999-01-01

243

Mechanisms of Human Arrhythmia Syndromes: Abnormal Cardiac Macromolecular Interactions  

NSDL National Science Digital Library

Many cardiac ion channels exist within macromolecular signaling complexes, comprised of pore-forming subunits that associate with auxiliary subunits, regulatory enzymes, and targeting proteins. This complex protein assembly ensures proper modulation of channel activity and ion homeostasis. The association of genetic defects in regulatory and targeting proteins to inherited arrhythmia syndromes has led to a better understanding of the critical role these proteins play in ion channel modulation.

2007-10-01

244

Patch-clamp detection of macromolecular translocation along nuclear pores  

Microsoft Academic Search

The present paper reviews the application of patch-clamp principles to the detection and measurement of macromolecular translocation along the nuclear pores. We demonstrate that the tight-seal 'gigaseal' be- tween the pipette tip and the nuclear membrane is possible in the presence of fully operational nuclear pores. We show that the ability to form a gigaseal in nucleus-attached configurations does not

J. O. Bustamante; W. A. Varanda

1998-01-01

245

Effects of Cannabinoids on Macromolecular Synthesis in Isolated Spermatogenic Cells  

Microsoft Academic Search

Effects of ?9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD) (1, 3 or 5 ?M for 2 h) on macromolecular synthesis were investigated in homogeneous populations of pachytene spermatocytes and round spermatids obtained from CD-1 mice. Incorporation of 3H-uridine into the acid-insoluble fraction was used as an index of RNA synthesis. Treatment of pachytene spermatocytes with 5 ?M THC, CBN and

S. K. Tilak; A. M. Zimmerman

1984-01-01

246

A decade of user operation on the macromolecular crystallography MAD beamline ID14-4 at the ESRF  

PubMed Central

ID14-4 at the ESRF is the first tunable undulator-based macromolecular crystallography beamline that can celebrate a decade of user service. During this time ID14-4 has not only been instrumental in the determination of the structures of biologically important molecules but has also contributed significantly to the development of various instruments, novel data collection schemes and pioneering radiation damage studies on biological samples. Here, the evolution of ID14-4 over the last decade is presented, and some of the major improvements that were carried out in order to maintain its status as one of the most productive macromolecular crystallography beamlines are highlighted. The experimental hutch has been upgraded to accommodate a high-precision diffractometer, a sample changer and a large CCD detector. More recently, the optical hutch has been refurbished in order to improve the X-ray beam quality on ID14-4 and to incorporate the most modern and robust optical elements used at other ESRF beamlines. These new optical elements will be described and their effect on beam stability discussed. These studies may be useful in the design, construction and maintenance of future X-ray beamlines for macromolecular crystallography and indeed other applications, such as those planned for the ESRF upgrade. PMID:19844017

McCarthy, Andrew A.; Brockhauser, Sandor; Nurizzo, Didier; Theveneau, Pascal; Mairs, Trevor; Spruce, Darren; Guijarro, Matias; Lesourd, Marc; Ravelli, Raimond B. G.; McSweeney, Sean

2009-01-01

247

Macromolecular Assemblage in the Design of a Synthetic AIDS Vaccine  

NASA Astrophysics Data System (ADS)

We describe a peptide vaccine model based on the mimicry of surface coat protein of a pathogen. This model used a macromolecular assemblage approach to amplify peptide antigens in liposomes or micelles. The key components of the model consisted of an oligomeric lysine scaffolding to amplify peptide antigens covalently 4-fold and a lipophilic membrane-anchoring group to further amplify noncovalently the antigens many-fold in liposomal or micellar form. A peptide antigen derived from the third variable domain of glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1), consisting of neutralizing, T-helper, and T-cytotoxic epitopes, was used in a macromolecular assemblage model (HIV-1 linear peptide amino acid sequence 308-331 in a tetravalent multiple antigen peptide system linked to tripalmitoyl-S-glycerylcysteine). The latter complex, in liposome or micelle, was used to immunize mice and guinea pigs without any adjuvant and found to induce gp120-specific antibodies that neutralize virus infectivity in vitro, elicit cytokine production, and prime CD8^+ cytotoxic T lymphocytes in vivo. Our results show that the macromolecular assemblage approach bears immunological mimicry of the gp120 of HIV virus and may lead to useful vaccines against HIV infection.

Defoort, Jean-Philippe; Nardelli, Bernardetta; Huang, Wolin; Ho, David D.; Tam, James P.

1992-05-01

248

Layer-by-layer polypeptide macromolecular assemblies-mediated synthesis of mesoporous silica and gold nanoparticle/mesoporous silica tubular nanostructures.  

PubMed

A simple and versatile approach is proposed to use the LbL-assembled polypeptide macromolecular assemblies as mediating agents and templates for directed growth of gold nanoparticles and biomimetic silica mineralization, allowing the synthesis of polypeptide/silica and polypeptide/gold nanoparticle/silica composite materials, as well as mesoporous silica (meso-SiO2) and gold nanoparticle/mesoporous silica (Au NP/meso-SiO2). The formation of tubular nanostructures was demonstrated by silicification and growth of gold nanoparticles within macromolecular assemblies formed by poly(L-lysine) (PLL) and poly(L-glutamic acid) (PLGA) using polycarbonate membranes as templates. The experimental data revealed that the silicified macromolecular assemblies adopted mainly sheet/turn conformation. The as-prepared mesoporous silica materials possessed well-defined tubular structures with pore size and porosity depending on the size of sheet/turn aggregates, which is a function of the molecular weight of polypeptides. The directed growth of Au NP and subsequent silica mineralization in the macromolecular assembly resulted in Au NP/meso-SiO2 tubes with uniform nanoparticle size and the as-prepared materials exhibited promising catalytic activity toward the reduction of p-nitrophenol. This approach provides a facile and general method to synthesize organic-inorganic composite materials, oxide and metal-oxide nanomaterials with different compositions and structures. PMID:21319781

Jan, Jeng-Shiung; Chuang, Tzu-Han; Chen, Po-Jui; Teng, Hsisheng

2011-03-15

249

Cell fine structure and function - Past and present  

NASA Technical Reports Server (NTRS)

Electron microscopic studies of nerve membrane fine structure, discussing cell membrane multienzyme and macromolecular energy and information transduction, protein synthesis and nucleic acids interrelations

Fernandez-Moran, H.

1970-01-01

250

Use of Plastic Capillaries for Macromolecular Crystallization  

NASA Technical Reports Server (NTRS)

Methods of crystallization of biomolecules in plastic capillaries (Nalgene 870 PFA tubing) are presented. These crystallization methods used batch, free-interface liquid- liquid diffusion alone, or a combination with vapor diffusion. Results demonstrated growth of crystals of test proteins such as thaumatin and glucose isomerase, as well as protein studied in our laboratory such dihydrolipoamide dehydrogenase. Once the solutions were loaded in capillaries, they were stored in the tubes in frozen state at cryogenic temperatures until the desired time of activation of crystallization experiments.

Potter, Rachel R.; Hong, Young-Soo; Ciszak, Ewa M.

2003-01-01

251

Destruction of Tissue, Cells and Organelles in Type 1 Diabetic Rats Presented at Macromolecular Resolution  

PubMed Central

Finding alternatives for insulin therapy and making advances in etiology of type 1 diabetes benefits from a full structural and functional insight into Islets of Langerhans. Electron microscopy (EM) can visualize Islet morphology at the highest possible resolution, however, conventional EM only provides biased snapshots and lacks context. We developed and employed large scale EM and compiled a resource of complete cross sections of rat Islets during immuno-destruction to provide unbiased structural insight of thousands of cells at macromolecular resolution. The resource includes six datasets, totalling 25.000 micrographs, annotated for cellular and ultrastructural changes during autoimmune diabetes. Granulocytes are attracted to the endocrine tissue, followed by extravasation of a pleiotrophy of leukocytes. Subcellullar changes in beta cells include endoplasmic reticulum stress, insulin degranulation and glycogen accumulation. Rare findings include erythrocyte extravasation and nuclear actin-like fibers. While we focus on a rat model of autoimmune diabetes, our approach is general applicable. PMID:23652855

Ravelli, Raimond B. G.; Kalicharan, Ruby D.; Avramut, M. Cristina; Sjollema, Klaas A.; Pronk, Joachim W.; Dijk, Freark; Koster, Abraham J.; Visser, Jeroen T. J.; Faas, Frank G. A.; Giepmans, Ben N. G.

2013-01-01

252

Thermodynamics and Statistical Mechanics of Macromolecular Systems  

NASA Astrophysics Data System (ADS)

Preface and outline; 1. Introduction; 2. Statistical mechanics: a modern review; 3. The complexity of minimalistic lattice models for protein folding; 4. Monte Carlo and chain growth methods for molecular simulations; 5. First insights to freezing and collapse of flexible polymers; 6. Crystallization of elastic polymers; 7. Structural phases of semiflexible polymers; 8. Generic tertiary folding properties of proteins in mesoscopic scales; 9. Protein folding channels and kinetics of two-state folding; 10. Inducing generic secondary structures by constraints; 11. Statistical analyses of aggregation processes; 12. Hierarchical nature of phase transitions; 13. Adsorption of polymers at solid substrates; 14. Hybrid protein-substrate interfaces; 15. Concluding remarks and outlook; Notes; References; Index.

Bachmann, Michael

2014-04-01

253

INTERNATIONAL Macromolecular crystal growth and optimisation methods  

E-print Network

. Athens Membrane proteins: the paradigm of nicotinic acetylcholine receptors in muscle and nerve Dr of the E.U. "TOPCRYST" project for Imperial College The joys and challenges of crystallising proteins, Ireland Crystallizing Membrane Proteins for Structure-Function Studies Using Lipidic Systems Professor

254

Macromolecular Monomers for the Synthesis of Hydrogel Niches and Their Application in Cell Encapsulation and Tissue Engineering  

PubMed Central

Hydrogels formed from the photoinitiated, solution polymerization of macromolecular monomers present distinct advantages as cell delivery materials and are enabling researchers to three-dimensionally encapsulate cells within diverse materials that mimic the extracellular matrix and support cellular viability. Approaches to synthesize gels with biophysically and biochemically controlled microenvironments are becoming increasingly important, and require strategies to control gel properties (e.g., degradation rate and mechanism) on multiple time and size scales. Furthermore, biological responses of gel-encapsulated cells can be promoted by hydrogel degradation products, as well as by the release of tethered biologically relevant molecules. PMID:19461945

Nuttelman, Charles R.; Rice, Mark A.; Rydholm, Amber E.; Salinas, Chelsea N.; Shah, Darshita N.

2008-01-01

255

Spatial structures in microtubular solutions requiring a sustained energy source  

Microsoft Academic Search

MICROTUBULES are believed to be the principal organizers of the cell interior1. Cells respond to a variety of stimuli by modifying the spatial distribution of the microtubules. These effects are central to cell division and morphogenesis2, and embryo development3. During embryo development, macroscopic patterns are frequently observed3. Here we report that microtubular solutions spontaneously form alternating white and dark stripes

J. Tabony; D. Job

1990-01-01

256

Implementation and performance of SIBYLS: a dual endstation small-angle X-ray scattering and macromolecular crystallography beamline at the Advanced Light Source  

PubMed Central

The SIBYLS beamline (12.3.1) of the Advanced Light Source at Lawrence Berkeley National Laboratory, supported by the US Department of Energy and the National Institutes of Health, is optimized for both small-angle X-ray scattering (SAXS) and macromolecular crystallography (MX), making it unique among the world’s mostly SAXS or MX dedicated beamlines. Since SIBYLS was commissioned, assessments of the limitations and advantages of a combined SAXS and MX beamline have suggested new strategies for integration and optimal data collection methods and have led to additional hardware and software enhancements. Features described include a dual mode monochromator [containing both Si(111) crystals and Mo/B4C multilayer elements], rapid beamline optics conversion between SAXS and MX modes, active beam stabilization, sample-loading robotics, and mail-in and remote data collection. These features allow users to gain valuable insights from both dynamic solution scattering and high-resolution atomic diffraction experiments performed at a single synchrotron beamline. Key practical issues considered for data collection and analysis include radiation damage, structural ensembles, alternative conformers and flexibility. SIBYLS develops and applies efficient combined MX and SAXS methods that deliver high-impact results by providing robust cost-effective routes to connect structures to biology and by performing experiments that aid beamline designs for next generation light sources. PMID:23396808

Classen, Scott; Hura, Greg L.; Holton, James M.; Rambo, Robert P.; Rodic, Ivan; McGuire, Patrick J.; Dyer, Kevin; Hammel, Michal; Meigs, George; Frankel, Kenneth A.; Tainer, John A.

2013-01-01

257

The prestressability problem of tensegrity structures: some analytical solutions  

Microsoft Academic Search

In this paper we formulate the general prestressability conditions for tensegrity structures. These conditions are expressed as a set of nonlinear equations and inequalities on the tendon tensions. Several examples of tensegrity structures for which the prestressability conditions can be analytically solved are then presented.

Cornel Sultan; Martin Corless; Robert E. Skelton

2001-01-01

258

NMR solution structure of the human prion protein  

Microsoft Academic Search

The NMR structures of the recombinant human prion protein, hPrP(23-230), and two C-terminal fragments, hPrP(90-230) and hPrP(121-230), include a globular domain extending from residues 125-228, for which a detailed structure was obtained, and an N-terminal flexibly disordered \\

Ralph Zahn; Aizhuo Liu; Thorsten Lührs; Roland Riek; Christine von Schroetter; Francisco López García; Martin Billeter; Luigi Calzolai; Gerhard Wider; Kurt Wüthrich

2000-01-01

259

Comparison of the crystal and solution structures of calmodulin and troponin C  

SciTech Connect

X-ray solution scattering data from skeletal muscle troponin C and from calmodulin have been measured. Modeling studies based on the crystal structure coordinates for these proteins show discrepancies between the solution data and the crystal structure that indicate that if the size and shape of the globular domains are the same in solution as in the crystal, the distances between them must be smaller by several angstroms. Bringing the globular domains closer together requires structural changes in the interconnecting helix that joins them.

Heidorn, D.B.; Trewhella, J.

1988-02-09

260

Macromolecular Micromovements: How RNA Polymerase Translocates  

PubMed Central

Multisubunit DNA-dependent RNA polymerases synthesize RNA molecules thousands of nucleotides long. The reiterative reaction of nucleotide condensation occurs at rates of tens of nucleotides per second, invariably linked to the translocation of the enzyme along the DNA template, or threading of the DNA and the nascent RNA molecule through the enzyme. Reiteration of the nucleotide addition/translocation cycle without dissociation from the DNA and RNA requires both iso- and metamorphic conformational flexibility of a magnitude substantial enough to accommodate the requisite molecular motions. Here we review some of the more recently acquired insights into the structural flexibility and morphic fluctuations of RNA polymerases and their mechanistic implications. PMID:19889534

Svetlov, Vladimir; Nudler, Evgeny

2013-01-01

261

Structure and solution properties of sodium car?ymethyl cellulose  

Microsoft Academic Search

We have investigated the macroscopic properties of eight commerical samples of sodium car?ymethyl cellulose (Na-CMC) with molecular weights between 9000 and 360 000 g mol?1 and substitution degrees between 0.75 and 1.47 in aqueous solutions. From rheological and electric birefringence measurements (a.c. and d.c. methods) we distinguished four critical concentrations which depend on the molecular weight of the samples, the

H. Hoffmann; J. Hilbig

1997-01-01

262

Extended and flexible domain solution structure of the extracellular matrix protein anosmin-1 by X-ray scattering, analytical ultracentrifugation and constrained modelling.  

PubMed

Kallmann's syndrome corresponds to a loss of sense of smell and hypogonadotrophic hypogonadism. Defects in anosmin-1 result in the X-linked inherited form of Kallmann's syndrome. Anosmin-1 is an extracellular matrix protein comprised of an N-terminal, cysteine-rich (Cys-box) domain and a whey acidic protein-like (WAP) domain, followed by four fibronectin type III (FnIII) domains. The solution structures of recombinant proteins containing the first three domains (PIWF1) and all six domains (PIWF4) were determined by X-ray scattering and analytical ultracentrifugation. Guinier analyses showed that PIWF1 and PIWF4 have different radii of gyration (R(G)) values of 3.1 nm and 6.7 nm, respectively, but similar cross-sectional radii of gyration (R(XS)) values of 1.5 nm and 1.9 nm, respectively. Distance distribution functions showed that the maximum lengths of PIWF1 and PIWF4 were 11 nm and 23 nm, respectively. Analytical ultracentrifugation gave sedimentation coefficients of 2.52 S and 3.55 S for PIWF1 and PIWF4, respectively. The interpretation of the scattering data by constrained modelling requires homology models for all six domains in anosmin-1. While models were already available for the WAP and FnIII domains, searches suggested the Cys-box domain may resemble the cysteine-rich region of the insulin-like growth factor receptor. Automated constrained molecular modelling based on joining the anosmin-1 domains with structurally randomised linkers resulted in 10,000 models for anosmin-1. A trial-and-error search showed that about 0.1-1.4% of these models fitted the X-ray data. The best models showed that the three domains and six domains in PIWF1 and PIWF4, respectively, were extended. The inter-domain linkers in anosmin-1 could not all be extended at the same time, and there was evidence for inter-domain flexibility. Models with folded-back domain arrangements do not fit the data. These solution structures account for the known biological function of anosmin-1, in particular its ability to interact with its three macromolecular ligands. PMID:15949815

Hu, Youli; Sun, Zhe; Eaton, Julian T; Bouloux, Pierre M G; Perkins, Stephen J

2005-07-15

263

Polaron delocalization in ladder macromolecular systems.  

PubMed

Organic macromolecules with conjugated building blocks have been the focus of extensive research that is motivated, in part, by the potential to create optical and electronic devices. We have shown that palladium-catalyzed amination can assemble triarylamine ladder materials with extended structures. Two ladder macromolecules have been prepared in high yields by a series of twelve or sixteen C-N coupling reactions. Studies of the electronic and optical properties of neutral and oxidized forms of the ladder structures were conducted. The optical and electronic properties of the ladder systems are compared to those of the linear tetra-phenyl-p-phenylenediamine as well as the tetra-p-anisyl-p-tetraazacyclophane. The electrochemistry of the ladder systems consists of a multiwave voltammogram with a relatively low first oxidation potential. Electron paramagnetic resonance spectroscopy of the ladder systems suggests the presence of a large density of delocalized polarons. Linear absorption measurements of the chemically oxidized ladders revealed both polaron and intervalence absorption bands. Steady-state and time-resolved fluorescence measurements were also carried out to characterize the dynamics in these novel systems. PMID:15969589

Yan, X Z; Pawlas, J; Goodson, T; Hartwig, J F

2005-06-29

264

Type IV Pilus: One Architectural Problem, Many Structural Solutions.  

PubMed

Type IV pili are long appendages found at the surface of many bacteria, composed of an oligomerized pilin protein and involved in processes such as adherence, motility and DNA transfer. In this issue of Structure, Piepenbrink and colleagues report the first structure a major pilin from a Gram-positive bacterium, revealing an unprecedented stabilization mechanism that may have implications for pilus evolution. PMID:25651057

Bergeron, Julien R C; Sgourakis, Nikolaos G

2015-02-01

265

MUFOLD: A new solution for protein 3D structure prediction  

PubMed Central

There have been steady improvements in protein structure prediction during the past 2 decades. However, current methods are still far from consistently predicting structural models accurately with computing power accessible to common users. Toward achieving more accurate and efficient structure prediction, we developed a number of novel methods and integrated them into a software package, MUFOLD. First, a systematic protocol was developed to identify useful templates and fragments from Protein Data Bank for a given target protein. Then, an efficient process was applied for iterative coarse-grain model generation and evaluation at the C? or backbone level. In this process, we construct models using interresidue spatial restraints derived from alignments by multidimensional scaling, evaluate and select models through clustering and static scoring functions, and iteratively improve the selected models by integrating spatial restraints and previous models. Finally, the full-atom models were evaluated using molecular dynamics simulations based on structural changes under simulated heating. We have continuously improved the performance of MUFOLD by using a benchmark of 200 proteins from the Astral database, where no template with >25% sequence identity to any target protein is included. The average root-mean-square deviation of the best models from the native structures is 4.28 Å, which shows significant and systematic improvement over our previous methods. The computing time of MUFOLD is much shorter than many other tools, such as Rosetta. MUFOLD demonstrated some success in the 2008 community-wide experiment for protein structure prediction CASP8. PMID:19927325

Zhang, Jingfen; Wang, Qingguo; Barz, Bogdan; He, Zhiquan; Kosztin, Ioan; Shang, Yi; Xu, Dong

2010-01-01

266

Solution softening in magnesium alloys: the effect of solid solutions on the dislocation core structure and nonbasal slip.  

PubMed

There is a pressing need to improve the ductility of magnesium alloys so that they can be applied as lightweight structural materials. In this study, a mechanism for enhancing the ductility of magnesium alloys has been pursued using the atomistic method. The generalized stacking fault (GSF) energies for basal and prismatic planes in magnesium were calculated by using density functional theory, and the effect of the GSF energy on the dislocation core structures was examined using a semidiscrete variational Peierls-Nabarro model. Yttrium was found to have an anomalous influence on the solution softening owing to a reduction in the GSF energy gradient. PMID:23220883

Tsuru, T; Udagawa, Y; Yamaguchi, M; Itakura, M; Kaburaki, H; Kaji, Y

2013-01-16

267

Solution Structure of the Conserved Hypothetical Protein Rv2302 from Mycobacterium tuberculosis.  

SciTech Connect

The hypothetical Mycobacterium tuberculosis protein RV2302 (80 residues, MW = 8.6 kDa) has been characterized using nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy. Size exclusion chromatography and NMR spectroscopy suggest that RV2302 is as a monomer is solution. Circular dichroism spectroscopy indicates the protein is structured in solution, but, irreversible unfolds upon heating with an inflection point of {approx}48 C. Using NMR based methods we determined the solution structure of RV2302. The protein contains a five strand, anti-parallel b-sheet core with one C-terminal a-helix (A65-A75) nestled against its side. Dali searches using the structure closest to the average structure did not identify any high similarities to any other known protein structure. Consequently, the structure of Rv2302 may potentially represent a novel protein fold.

Buchko, Garry W.; Kim, Chang Y.; Terwilliger, Thomas C.; Kennedy, Michael A.

2006-08-01

268

The effects of solution parameters on the structure of polyethylene single crystals  

E-print Network

to answer ares (1) Must are the effects of tho thermodynamic solution parameters? temperature, concentration? type of solvent? molecular weight of solute, and degree of supercocling? on the structure and morphology of solution grown? single crystals... and sine from a four-sided lonenge, with its sides 2p longe to an elongated hexagon with sides measuring 50p or more. The purpose of one facet of this research program has been to learn why and~ if possible~ how these variations secure Hassett...

Ashburn, Donald George

1964-01-01

269

Capillary electrophoretic separation of structurally similar solutes in noncross-linked poly(acrylamide-co-N-isopropylacrylamide) solution.  

PubMed

Noncross-linked acrylamide (AA)-N-isopropylacrylamide (IPAAm) copolymers have been used as a buffer additive in capillary electrophoretic separation of structurally similar small solutes. Seven kinds of barbiturates and five kinds of dansylated (Dns) amino acids, which have different hydrophobic side chains, were separated on poly(AA-co-IPAAm)-filled columns and on AA polymer-filled columns under the condition of totally eliminating the contribution of electroosmotic flow (EOF). It is known that the copolymer containing IPAAm has thermosensitive properties, and the hydrophobicity of its surface changes with surrounding temperature. In this investigation, therefore, the effects of an isopropyl group in the copolymer on the electrophoretic separation of the small solutes were studied by comparing the two polymer-filled columns at ambient temperature and at elevated temperature. Although slight differences in migration behavior were observed at ambient temperature between the columns filled with these two polymer solutions, obvious differences in the separation of the solutes were observed at elevated temperature. The observed changes on the migration behavior might be caused by the interaction between copolymer chains exhibiting hydrophobic property and the solute. PMID:9420164

Sawada, H; Jinno, K

1997-10-01

270

Argentivorous molecules: structural evidence for Ag(+)-? interactions in solution.  

PubMed

Tetra-armed cyclens bearing aromatic side arms were prepared by the reductive amination of cyclen with substituted benzaldehydes. When equimolar amounts of Ag(+) ions were added to the ligands, the aromatic rings covered the Ag(+) ions incorporated in the ligand cavities, as if the aromatic ring "petals" caught the Ag(+) ions in the way an insectivorous plant (Venus flytrap) catches insects. The ligands are called "argentivorous molecules". Evidence of intramolecular Ag(+)-? interactions in solution and in the solid state is reported. PMID:22928524

Habata, Yoichi; Ikeda, Mari; Yamada, Sachiko; Takahashi, Hiroki; Ueno, Sumiko; Suzuki, Takatoshi; Kuwahara, Shunsuke

2012-09-01

271

Methods to determine the pressure dependence of the molecular order parameter in (bio)macromolecular fibres.  

PubMed

The experimental realization and an algorithm for analysing the pressure dependence of the molecular order parameter of specific structural moieties in (bio)macromolecular fibres are described. By employing a diamond anvil cell (DAC) the polarization-dependent IR-transmission and in parallel, using an integrated microscope, the macroscopic orientation of the fibres is determined. This enables one to separate between order and disorder at macroscopic and microscopic scales. Using the example of spider silk the pressure dependence of the molecular order parameter of alanine groups being located within nano-crystalline building blocks is deduced and found to decrease reversibly by 0.01 GPa(-1) when varying the external hydrostatic pressure between 0 and 3 GPa. PMID:25557527

Anton, Arthur Markus; Gutsche, Christof; Kossack, Wilhelm; Kremer, Friedrich

2015-01-28

272

Phase transitions of macromolecular microsphere composite hydrogels based on the stochastic Cahn-Hilliard equation  

NASA Astrophysics Data System (ADS)

We use the stochastic Cahn-Hilliard equation to simulate the phase transitions of the macromolecular microsphere composite (MMC) hydrogels under a random disturbance. Based on the Flory-Huggins lattice model and the Boltzmann entropy theorem, we develop a reticular free energy suit for the network structure of MMC hydrogels. Taking the random factor into account, with the time-dependent Ginzburg-Landau (TDGL) mesoscopic simulation method, we set up a stochastic Cahn-Hilliard equation, designated herein as the MMC-TDGL equation. The stochastic term in the equation is constructed appropriately to satisfy the fluctuation-dissipation theorem and is discretized on a spatial grid for the simulation. A semi-implicit difference scheme is adopted to numerically solve the MMC-TDGL equation. Some numerical experiments are performed with different parameters. The results are consistent with the physical phenomenon, which verifies the good simulation of the stochastic term.

Li, Xiao; Ji, Guanghua; Zhang, Hui

2015-02-01

273

Engineering Human Immunodeficiency Virus 1 Protease Heterodimers as Macromolecular Inhibitors of Viral Maturation  

NASA Astrophysics Data System (ADS)

Dimerization of human immunodeficiency virus type 1 protease (HIV-1 PR) monomers is an essential prerequisite for viral proteolytic activity and the subsequent generation of infectious virus particles. Disruption of the dimer interface inhibits this activity as does formation of heterodimers between wild-type and defective monomers. A structure-based approach was used to identify amino acid substitutions at the dimer interface of HIV-1 PR that facilitate preferential association of heterodimers and inhibit self-association of the defective monomers. Expression of the designed PR monomers inhibits activity of wild-type HIV-1 PR and viral infectivity when assayed in an ex vivo model system. These results show that it is possible to design PR monomers as macromolecular inhibitors that may provide an alternative to small molecule inhibitors for the treatment of HIV infection.

McPhee, Fiona; Good, Andrew C.; Kuntz, Irwin D.; Craik, Charles S.

1996-10-01

274

Finite element solution of transient fluid-structure interaction problems  

NASA Technical Reports Server (NTRS)

A finite element approach using NASTRAN is developed for solving time-dependent fluid-structure interaction problems, with emphasis on the transient scattering of acoustic waves from submerged elastic structures. Finite elements are used for modeling both structure and fluid domains to facilitate the graphical display of the wave motion through both media. For the liquid, the use of velocity potential as the fundamental unknown results in a symmetric matrix equation. The approach is illustrated for the problem of transient scattering from a submerged elastic spherical shell subjected to an incident tone burst. The use of an analogy between the equations of elasticity and the wave equation of acoustics, a necessary ingredient to the procedure, is summarized.

Everstine, Gordon C.; Cheng, Raymond S.; Hambric, Stephen A.

1991-01-01

275

Macromolecular Crowding as a Suppressor of Human IAPP Fibril Formation and Cytotoxicity  

PubMed Central

The biological cell is known to exhibit a highly crowded milieu, which significantly influences protein aggregation and association processes. As several cell degenerative diseases are related to the self-association and fibrillation of amyloidogenic peptides, understanding of the impact of macromolecular crowding on these processes is of high biomedical importance. It is further of particular relevance as most in vitro studies on amyloid aggregation have been performed in diluted solution which does not reflect the complexity of their cellular surrounding. The study presented here focuses on the self-association of the type-2 diabetes mellitus related human islet amyloid polypeptide (hIAPP) in various crowded environments including network-forming macromolecular crowding reagents and protein crowders. It was possible to identify two competing processes: a crowder concentration and type dependent stabilization of globular off-pathway species and a – consequently - retarded or even inhibited hIAPP fibrillation reaction. The cause of these crowding effects was revealed to be mainly excluded volume in the polymeric crowders, whereas non-specific interactions seem to be most dominant in protein crowded environments. Specific hIAPP cytotoxicity assays on pancreatic ?-cells reveal non-toxicity for the stabilized globular species, in contrast to the high cytotoxicity imposed by the normal fibrillation pathway. From these findings it can be concluded that cellular crowding is able to effectively stabilize the monomeric conformation of hIAPP, hence enabling the conduction of its normal physiological function and prevent this highly amyloidogenic peptide from cytotoxic aggregation and fibrillation. PMID:23922768

Seeliger, Janine; Werkmüller, Alexander; Winter, Roland

2013-01-01

276

Structure and properties of loaded silica contacts during pressure solution: impedance spectroscopy measurements under hydrothermal conditions  

Microsoft Academic Search

In order to investigate directly the structure and properties of grain boundaries in silicate materials undergoing pressure solution, in situ measurements of these properties are required. We report electrical impedance spectroscopy measurements, performed, under hydrothermal conditions, on individual glass-glass and glass-quartz contacts undergoing pressure solution. Resulting estimates of the average grain boundary diffusivity product ( Z = Ddelta_{{av}} C^{*} )

R. van Noort; C. J. Spiers; C. J. Peach

2011-01-01

277

Formation and thermodynamic stability of (polymer + porphyrin) supramolecular structures in aqueous solutions  

E-print Network

be tuned through (polymer + porphyrin) (host + guest) binding in solution. This gives rise to the formation. However, (polymer + porphyrin) binding competes with porphyrin self-association in solution, and accurateFormation and thermodynamic stability of (polymer + porphyrin) supramolecular structures in aqueous

Annunziata, Onofrio

278

The importance of relict burrow structures and burrow irrigation in controlling sedimentary solute distributions  

NASA Astrophysics Data System (ADS)

Some areas of the seafloor, particularly the deep sea, are characterized by large numbers of apparently uninhabited or relict burrow structures formed by macrobenthic organisms. Because of low sedimentation rates or lack of physical disturbance these structures are stable for long periods of time and could potentially influence solute diffusion patterns in surface sediments. A two-dimensional diffusionreaction model which allows for diffusive rather than advective transport within stagnant, water-filled burrows demonstrates that, in the absence of advective irrigation, relict burrow structures are unlikely in most cases to significantly alter average solute distributions from those predicted by one-dimensional vertical models. This conclusion assumes changes in diffusive transport properties alone and does not account for any effects of relict structures on reaction rates or physical ventilation of deposits by bottom currents. Significant changes (?5%) in solute distributions are generally produced only when the ratio of the halfdistance between burrows to relict burrow radii is ?10 and sedimentary diffusion coefficients are ?60% that in free solution. Because solute distributions in stagnant burrow waters are nearly that in surrounding sediment, sediment-water solute fluxes are also essentially unaffected by relict burrows except at extremely high abundances or fairly large differential diffusion rates between sediment and free solution. In contrast, even at low abundance, biologically irrigated or physically ventilated burrows produce major changes in solute transport and build-up patterns.

Aller, Robert C.

1984-10-01

279

Salt-stabilized globular protein structure in 7 M aqueous urea solution  

E-print Network

1 Salt-stabilized globular protein structure in 7 M aqueous urea solution V. Dötsch,1 G. Wider, G Hochschule- Hönggerberg, CH-8093 Zürich, Switzerland Keywords Protein folding; Urea denaturation; Salt changing the solution conditions. In this paper we describe the influence of various salts or non

Wider, Gerhard

280

Biophotonic probing of macromolecular transformations during apoptosis  

PubMed Central

We introduce here multiplex nonlinear optical imaging as a powerful tool for studying the molecular organization and its transformation in cellular processes, with the specific example of apoptosis. Apoptosis is a process of self-initiated cell death, critically important for physiological regulation and elimination of genetic disorders. Nonlinear optical microscopy, combining the coherent anti-Stokes Raman scattering (CARS) microscopy and two-photon excited fluorescence (TPEF), has been used for analysis of spatial distribution of major types of biomolecules: proteins, lipids, and nucleic acids in the cells while monitoring their changes during apoptosis. CARS imaging revealed that in the nuclei of proliferating cells, the proteins are distributed nearly uniformly, with local accumulations in several nuclear structures. We have found that this distribution is abruptly disrupted at the onset of apoptosis and is transformed to a progressively irregular pattern. Fluorescence recovery after photobleaching (FRAP) studies indicate that pronounced aggregation of proteins in the nucleoplasm of apoptotic cells coincides with a gradual reduction in their mobility. PMID:20615987

Pliss, Artem; Kuzmin, Andrey N.; Kachynski, Aliaksandr V.; Prasad, Paras N.

2010-01-01

281

ANOVA-HDMR structure of the higher order nodal diffusion solution  

SciTech Connect

Nodal diffusion methods still represent a standard in global reactor calculations, but employ some ad-hoc approximations (such as the quadratic leakage approximation) which limit their accuracy in cases where reference quality solutions are sought. In this work we solve the nodal diffusion equations utilizing the so-called higher-order nodal methods to generate reference quality solutions and to decompose the obtained solutions via a technique known as High Dimensional Model Representation (HDMR). This representation and associated decomposition of the solution provides a new formulation of the transverse leakage term. The HDMR structure is investigated via the technique of Analysis of Variance (ANOVA), which indicates why the existing class of transversely-integrated nodal methods prove to be so successful. Furthermore, the analysis leads to a potential solution method for generating reference quality solutions at a much reduced calculational cost, by applying the ANOVA technique to the full higher order solution. (authors)

Bokov, P. M.; Prinsloo, R. H.; Tomasevic, D. I. [South African Nuclear Energy Corporation - Necsa, Building 1900, P.O. Box 582, 0001 Pretoria (South Africa)

2013-07-01

282

A structured multi-block solution-adaptive mesh algorithm with mesh quality assessment  

Microsoft Academic Search

The dynamic solution adaptive grid algorithm, DSAGA3D, is extended to automatically adapt 2-D structured multi-block grids, including adaption of the block boundaries. The extension is general, requiring only input data concerning block structure, connectivity, and boundary conditions. Imbedded grid singular points are permitted, but must be prevented from moving in space. Solutions for workshop cases 1 and 2 are obtained

Clint L. Ingram; Kelly R. Laflin; D. Scott McRae

1995-01-01

283

Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences*  

PubMed Central

Expected and observed effects of volume exclusion on the free energy of rigid and flexible macromolecules in crowded and confined systems, and consequent effects of crowding and confinement on macromolecular reaction rates and equilibria are summarized. Findings from relevant theoretical/simulation and experimental literature published from 2004 onward are reviewed. Additional complexity arising from the heterogeneity of local environments in biological media, and the presence of nonspecific interactions between macromolecules over and above steric repulsion are discussed. Theoretical and experimental approaches to the characterization of crowding- and confinement-induced effects in systems approaching the complexity of living organisms are suggested. PMID:18573087

Zhou, Huan-Xiang; Rivas, Germán; Minton, Allen P.

2009-01-01

284

Element-by-element Solution Procedures for Nonlinear Structural Analysis  

NASA Technical Reports Server (NTRS)

Element-by-element approximate factorization procedures are proposed for solving the large finite element equation systems which arise in nonlinear structural mechanics. Architectural and data base advantages of the present algorithms over traditional direct elimination schemes are noted. Results of calculations suggest considerable potential for the methods described.

Hughes, T. J. R.; Winget, J. M.; Levit, I.

1984-01-01

285

Molecular Structure of Hydrochloric acid (if in aqueous solution)  

NSDL National Science Digital Library

Hydrochloric acid (or hydrogen chloride) can be a colorless liquid with a sharp odor or a colorless to slightly yellow gas. It is a strong acid (it ionizes completely in aqueous solution) and highly corrosive. HCl is widely used as a laboratory reagent in the production of chlorides, in organic synthesis, ore reduction, hydrolyzing of starch and proteins, in the preparation of various food products, metal cleaning and pickling, for instance, and pharmaceutics acidifier. HCI is widely used in the manufacture e.g., in the conversion of cornstarch to syrup, in sugar refining, electroplating, soap refining, leather tanning etc. It is also used to remove scale and dust from boilers and heat exchange equipment, to clean membranes in desalination plants, increase oil well output and prepare metals for coatings.

2002-09-10

286

On Computing Multiple Solutions of Nonlinear PDEs Without Variational Structure  

E-print Network

. : : : : : 29 2.5 Case 2. C = 2. Pro les and contours of eigenfunctions u1; :::; u 9. : : : : : 30 2.6 Solutions according to their Morse index. : : : : : : : : : : : : : : : : : : 38 2.7 C = 0:25; uC = 0:6687; (uC) = 2:2361. Pro les and contours... of eigenfunctions u1; :::; u 7 with (ui) = 2:2361, 6:4473, 7:1233, 16:3673, 36:1560, 36:7853, 155:9402 and kuikH = 0:9457, 1:8468, 2:0748, 2:5229, 3:5020, 3:8904, 7:6583. : : : : : : : : : : : : : : : : : : : : : : : : : : : : 43 2.8 C = 1:25; uC = 1; (uC) = 5...

Wang, Changchun

2012-07-16

287

Effect of Macromolecular Crowding on Protein Binding Stability: Modest Stabilization and Significant Biological Consequences  

E-print Network

Macromolecular crowding has long been known to significantly affect protein oligomerization, and yet no direct of crowding, e.g., by a reduction in cell volume or a slowdown in protein degradation, both of whichEffect of Macromolecular Crowding on Protein Binding Stability: Modest Stabilization

Weston, Ken

288

Insights into the disparate action of osmolytes and macromolecular crowders on amyloid formation  

E-print Network

-association of alternatively folded proteins or peptides.1 In diseases ranging from Alzheimer's to Rheumatoid arthritis: macromolecular crowders and compatible osmolytes. We have recently found that addition of macromolecular PEG only favoring additional fibril formation. Our analysis provides first hints that cosolutes act not only

Harries, Daniel

289

Atomistic Modeling of Macromolecular Crowding Predicts Modest Increases in Protein Folding and Binding Stability  

E-print Network

Atomistic Modeling of Macromolecular Crowding Predicts Modest Increases in Protein Folding that macromolecular crowding can increase protein folding stability, but depending on details of the models (e.g., how on the effects of macro- molecular crowding on protein folding and binding stability has been reached. Crowders

Weston, Ken

290

Shear-induced structure in polymer–clay nanocomposite solutions  

Microsoft Academic Search

The equilibrium structure and shear response of model polymer–clay nanocomposite gels are measured using X-ray scattering, light scattering, optical microscopy, and rheometry. The suspensions form physical gels via the “bridging” of neighboring colloidal clay platelets by the polymer, with reversible adsorption of polymer segments onto the clay surface providing a short-range attractive force. As the flow disrupts this transient network,

S. Lin-Gibson; H. Kim; G. Schmidt; C. C. Han; E. K. Hobbie

2004-01-01

291

Methods for controlling structure and photophysical properties in polyfluorene solutions and gels.  

PubMed

Knowledge of the phase behavior of polyfluorene solutions and gels has expanded tremendously in recent years. The relationship between the structure formation and photophysics is known at the quantitative level. The factors which we understand control these relationships include virtually all important materials parameters such as solvent quality, side chain branching, side chain length, molecular weight, thermal history and myriad functionalizations. This review describes advances in controlling structure and photophysical properties in polyfluorene solutions and gels. It discusses the demarcation lines between solutions, gels, and macrophase separation in conjugated polymers and reviews essential solid state properties needed for understanding of solutions. It gives an insight into polyfluorene and polyfluorene beta phase in solutions and gels and describes all the structural levels in solvent matrices, ranging from intramolecular structures to the diverse aggregate classes and network structures and agglomerates of these units. It goes on to describe the kinetics and thermodynamics of these structures. It details the manifold molecular parameters used in their control and continues with the molecular confinement and touches on permanently cross-linked networks. Particular focus is placed on the experimental results of archetypical polyfluorenes and solvent matrices and connection between structure and photonics. A connection is also made to the mean field type theories of hairy-rod like polymers. This altogether allows generalizations and provides a guideline for materials scientists, synthetic chemists and device engineers as well, for this important class of semiconductor, luminescent polymers. PMID:23341026

Knaapila, Matti; Monkman, Andrew P

2013-02-25

292

Assembly of a polytopic membrane protein structure from the solution structures of overlapping peptide fragments of bacteriorhodopsin.  

PubMed Central

Three-dimensional structures of only a handful of membrane proteins have been solved, in contrast to the thousands of structures of water-soluble proteins. Difficulties in crystallization have inhibited the determination of the three-dimensional structure of membrane proteins by x-ray crystallography and have spotlighted the critical need for alternative approaches to membrane protein structure. A new approach to the three-dimensional structure of membrane proteins has been developed and tested on the integral membrane protein, bacteriorhodopsin, the crystal structure of which had previously been determined. An overlapping series of 13 peptides, spanning the entire sequence of bacteriorhodopsin, was synthesized, and the structures of these peptides were determined by NMR in dimethylsulfoxide solution. These structures were assembled into a three-dimensional construct by superimposing the overlapping sequences at the ends of each peptide. Onto this construct were written all the distance and angle constraints obtained from the individual solution structures along with a limited number of experimental inter-helical distance constraints, and the construct was subjected to simulated annealing. A three-dimensional structure, determined exclusively by the experimental constraints, emerged that was similar to the crystal structure of this protein. This result suggests an alternative approach to the acquisition of structural information for membrane proteins consisting of helical bundles. PMID:11463644

Katragadda, M; Alderfer, J L; Yeagle, P L

2001-01-01

293

Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS)  

SciTech Connect

We present an efficient pipeline enabling high-throughput analysis of protein structure in solution with small angle X-ray scattering (SAXS). Our SAXS pipeline combines automated sample handling of microliter volumes, temperature and anaerobic control, rapid data collection and data analysis, and couples structural analysis with automated archiving. We subjected 50 representative proteins, mostly from Pyrococcus furiosus, to this pipeline and found that 30 were multimeric structures in solution. SAXS analysis allowed us to distinguish aggregated and unfolded proteins, define global structural parameters and oligomeric states for most samples, identify shapes and similar structures for 25 unknown structures, and determine envelopes for 41 proteins. We believe that high-throughput SAXS is an enabling technology that may change the way that structural genomics research is done.

Hura, Greg L.; Menon, Angeli L.; Hammel, Michal; Rambo, Robert P.; Poole II, Farris L.; Tsutakawa, Susan E.; Jenney Jr, Francis E.; Classen, Scott; Frankel, Kenneth A.; Hopkins, Robert C.; Yang, Sungjae; Scott, Joseph W.; Dillard, Bret D.; Adams, Michael W. W.; Tainer, John A.

2009-07-20

294

A structured multi-block solution-adaptive mesh algorithm with mesh quality assessment  

NASA Technical Reports Server (NTRS)

The dynamic solution adaptive grid algorithm, DSAGA3D, is extended to automatically adapt 2-D structured multi-block grids, including adaption of the block boundaries. The extension is general, requiring only input data concerning block structure, connectivity, and boundary conditions. Imbedded grid singular points are permitted, but must be prevented from moving in space. Solutions for workshop cases 1 and 2 are obtained on multi-block grids and illustrate both increased resolution of and alignment with the solution. A mesh quality assessment criteria is proposed to determine how well a given mesh resolves and aligns with the solution obtained upon it. The criteria is used to evaluate the grid quality for solutions of workshop case 6 obtained on both static and dynamically adapted grids. The results indicate that this criteria shows promise as a means of evaluating resolution.

Ingram, Clint L.; Laflin, Kelly R.; Mcrae, D. Scott

1995-01-01

295

The density, viscosity and structural properties of aqueous ethambutol hydrochloride solutions  

NASA Astrophysics Data System (ADS)

Ethambutol (EMB) is a bacteriostatic antimycobacterial drug prescribed to treat tuberculosis. It is bacteriostatic against actively growing TB bacilli. The density and viscosity of aqueous ethambutol hydrochloride solutions have been studied at 298.15, 301.15 and 304.15 K and at different concentrations (0.255, 0.168, 0.128, 0.087, 0.041, and 0.023 mol dm-3). The apparent molar volume of these solutions for different temperatures and concentrations was calculated from the density data. The relative viscosities of drug solutions have been analysed by Jones-Dole equation. The limiting apparent molar volumes have been evaluated for different temperatures. The different properties have been used to study structural properties, structure formation and breaking properties of drug and solute-solvent interactions in solutions.

Deosarkar, S. D.; Puyad, A. L.; Kalyankar, T. M.

2012-05-01

296

Investigations on the structure of DMSO and acetone in aqueous solution  

SciTech Connect

Aqueous solutions of dimethyl sulfoxide (DMSO) and acetone have been investigated using neutron diffraction augmented with isotopic substitution and empirical potential structure refinement computer simulations. Each solute has been measured at two concentrations-1:20 and 1:2 solute:water mole ratios. At both concentrations for each solute, the tetrahedral hydrogen bonding network of water is largely unperturbed, though the total water molecule coordination number is reduced in the higher 1:2 concentrations. With higher concentrations of acetone, water tends to segregate into clusters, while in higher concentrations of DMSO the present study reconfirms that the structure of the liquid is dominated by DMSO-water interactions. This result may have implications for the highly nonideal behavior observed in the thermodynamic functions for 1:2 DMSO-water solutions.

McLain, Sylvia E [ORNL; Soper, Alan K [ORNL

2007-01-01

297

Solution structure of the HIV-1 exon splicing silencer 3.  

PubMed

Alternative splicing of the human immunodeficiency virus type 1 (HIV-1) genomic RNA is necessary to produce the complete viral protein complement, and aberrations in the splicing pattern impair HIV-1 replication. Genome splicing in HIV-1 is tightly regulated by the dynamic assembly/disassembly of trans host factors with cis RNA control elements. The host protein, heterogeneous nuclear ribonucleoprotein (hnRNP) A1, regulates splicing at several highly conserved HIV-1 3' splice sites by binding 5'-UAG-3' elements embedded within regions containing RNA structure. The physical determinants of hnRNP A1 splice site recognition remain poorly defined in HIV-1, thus precluding a detailed understanding of the molecular basis of the splicing pattern. Here, the three-dimensional structure of the exon splicing silencer 3 (ESS3) from HIV-1 has been determined using NMR spectroscopy. ESS3 adopts a 27-nucleotide hairpin with a 10-bp A-form stem that contains a pH-sensitive A(+)C wobble pair. The seven-nucleotide hairpin loop contains the high-affinity hnRNP-A1-responsive 5'-UAGU-3' element and a proximal 5'-GAU-3' motif. The NMR structure shows that the heptaloop adopts a well-organized conformation stabilized primarily by base stacking interactions reminiscent of a U-turn. The apex of the loop is quasi-symmetric with UA dinucleotide steps from the 5'-GAU-3' and 5'-UAGU-3' motifs stacking on opposite sides of the hairpin. As a step towards understanding the binding mechanism, we performed calorimetric and NMR titrations of several hnRNP A1 subdomains into ESS3. The data show that the UP1 domain forms a high-affinity (K(d)=37.8±1.1 nM) complex with ESS3 via site-specific interactions with the loop. PMID:22154809

Levengood, Jeffrey D; Rollins, Carrie; Mishler, Clay H J; Johnson, Charles A; Miner, Grace; Rajan, Prashant; Znosko, Brent M; Tolbert, Blanton S

2012-01-27

298

Recent Major Improvements to the ALS Sector 5 MacromolecularCrystallography Beamlines  

SciTech Connect

Although the Advanced Light Source (ALS) was initially conceived primarily as a low energy (1.9GeV) 3rd generation source of VUV and soft x-ray radiation it was realized very early in the development of the facility that a multipole wiggler source coupled with high quality, (brightness preserving), optics would result in a beamline whose performance across the optimal energy range (5-15keV) for macromolecular crystallography (MX) would be comparable to, or even exceed, that of many existing crystallography beamlines at higher energy facilities. Hence, starting in 1996, a suite of three beamlines, branching off a single wiggler source, was constructed, which together formed the ALS Macromolecular Crystallography Facility. From the outset this facility was designed to cater equally to the needs of both academic and industrial users with a heavy emphasis placed on the development and introduction of high throughput crystallographic tools, techniques, and facilities--such as large area CCD detectors, robotic sample handling and automounting facilities, a service crystallography program, and a tightly integrated, centralized, and highly automated beamline control environment for users. This facility was immediately successful, with the primary Multiwavelength Anomalous Diffraction beamline (5.0.2) in particular rapidly becoming one of the foremost crystallographic facilities in the US--responsible for structures such as the 70S ribosome. This success in-turn triggered enormous growth of the ALS macromolecular crystallography community and spurred the development of five additional ALS MX beamlines all utilizing the newly developed superconducting bending magnets ('superbends') as sources. However in the years since the original Sector 5.0 beamlines were built the performance demands of macromolecular crystallography users have become ever more exacting; with growing emphasis placed on studying larger complexes, more difficult structures, weakly diffracting or smaller crystals, and on more rapidly screening larger numbers of candidate crystals; all of these requirements translate directly into a pressing need for increased flux, a tighter beam focus and faster detectors. With these growing demands in mind a major program of beamline and detector upgrades was initiated in 2004 with the goal of dramatically enhancing all aspects of beamline performance. Approximately $3 million in funding from diverse sources including NIH, LBL, the ALS, and the industrial and academic members of the beamline Participating Research Team (PRT), has been employed to develop and install new high performance beamline optics and to purchase the latest generation of CCD detectors. This project, which reached fruition in early 2007, has now fulfilled all of its original goals--boosting the flux on all three beamlines by up to 20-fold--with a commensurate reduction in exposure and data acquisition times for users. The performance of the Sector 5.0 beamlines is now comparable to that of the latest generation ALS superbend beamlines and, in the case of beamline 5.0.2, even surpasses it by a considerable margin. Indeed, the present performance of this beamline is now, once again, comparable to that envisioned for many MX beamlines planned or under construction on newer or higher energy machines.

Morton, Simon A.; Glossinger, James; Smith-Baumann, Alexis; McKean, John P.; Trame, Christine; Dickert, Jeff; Rozales, Anthony; Dauz,Azer; Taylor, John; Zwart, Petrus; Duarte, Robert; Padmore, Howard; McDermott, Gerry; Adams, Paul

2007-07-01

299

On the calculation of absolute macromolecular binding free energies  

PubMed Central

The standard framework for calculating the absolute binding free energy of a macromolecular association reaction A + B ? AB with an association constant KAB is to equate chemical potentials of the species on the left- and right-hand sides of this reaction and evaluate the chemical potentials from theory. This theory involves (usually hidden) assumptions about what constitutes the bound species, AB, and where the contribution of the solvent appears. We present here an alternative derivation that can be traced back to Bjerrum, in which the expectation value of KAB is obtained directly through the statistical mechanical method of evaluating its ensemble (Boltzmann-weighted) average. The generalized Bjerrum approach more clearly delineates: (i) the different contributions to binding; (ii) the origin of the much-discussed and somewhat controversial association entropy term; and (iii) where the solvent contribution appears. This approach also allows approximations required for practical evaluation of the binding constant in complex macromolecular systems, to be introduced in a well defined way. We provide an example, with application to test cases that illustrate a range of binding behavior. PMID:12149474

Luo, Hengbin; Sharp, Kim

2002-01-01

300

Isomerization kinetics of AT hook decapeptide solution structures  

PubMed Central

The mammalian high mobility group protein HMGA2 contains three DNA binding motifs associated with many physiological functions including oncogenesis, obesity, stem cell youth, human height, and human intelligence. In the present paper, trapped ion mobility spectrometry – mass spectrometry (TIMS-MS) has been utilized to study the conformational dynamics of the third DNA binding motif using the “AT hook” decapeptide unit (Lys1-Arg2-Prol3-Arg4-Gly5-Arg6-Prol7-Arg8-Lys9-Trp10, ATHP) as a function of the solvent state. Solvent state distributions were preserved during electrospray ion formation and multiple IMS bands were identified for the [M+2H]+2 and for the [M+3H]+3 charge states. Conformational isomer inter-conversion rates were measured as a function of the trapping time for the [M+2H]+2 and [M+3H]+3 charge states. Candidate structures were proposed for all IMS bands observed. Protonation site, proline residue conformation, and side chain orientations were identified as the main motifs governing the conformational inter-conversion processes. Conformational dynamics from the solvent state distribution to the gas-phase “de-solvated” state distribution demonstrated that ATHP is “structured”, and relative abundances are associated to the relative stability between the proposed conformers. The most stable ATHP [M+2H]+2 conformation at the “de-solvated” state corresponds to the AT-hook motif observed in AT-rich DNA regions. PMID:24364733

Schenk, Emily R.; Ridgeway, Mark E.; Park, Melvin A.; Leng, Fenfei; Fernandez-Lima, Francisco

2014-01-01

301

Isomerization kinetics of AT hook decapeptide solution structures.  

PubMed

The mammalian high mobility group protein HMGA2 contains three DNA binding motifs associated with many physiological functions including oncogenesis, obesity, stem cell youth, human height, and human intelligence. In the present paper, trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) has been utilized to study the conformational dynamics of the third DNA binding motif using the "AT hook" decapeptide unit (Lys(1)-Arg(2)-Prol(3)-Arg(4)-Gly(5)-Arg(6)-Prol(7)-Arg(8)-Lys(9)-Trp(10), ATHP) as a function of the solvent state. Solvent state distributions were preserved during electrospray ion formation, and multiple IMS bands were identified for the [M + 2H](2+) and for the [M + 3H](3+) charge states. Conformational isomer interconversion rates were measured as a function of the trapping time for the [M + 2H](2+) and [M + 3H](3+) charge states. Candidate structures were proposed for all IMS bands observed. Protonation site, proline residue conformation, and side chain orientations were identified as the main motifs governing the conformational interconversion processes. Conformational dynamics from the solvent state distribution to the gas-phase "de-solvated" state distribution demonstrated that ATHP is "structured", and relative abundances are associated with the relative stability between the proposed conformers. The most stable ATHP [M + 2H](2+) conformation at the "de-solvated" state corresponds to the AT hook motif observed in AT-rich DNA regions. PMID:24364733

Schenk, Emily R; Ridgeway, Mark E; Park, Melvin A; Leng, Fenfei; Fernandez-Lima, Francisco

2014-01-21

302

Application of in situ diffraction in high-throughput structure determination platforms.  

PubMed

Macromolecular crystallography (MX) is the most powerful technique available to structural biologists to visualize in atomic detail the macromolecular machinery of the cell. Since the emergence of structural genomics initiatives, significant advances have been made in all key steps of the structure determination process. In particular, third-generation synchrotron sources and the application of highly automated approaches to data acquisition and analysis at these facilities have been the major factors in the rate of increase of macromolecular structures determined annually. A plethora of tools are now available to users of synchrotron beamlines to enable rapid and efficient evaluation of samples, collection of the best data, and in favorable cases structure solution in near real time. Here, we provide a short overview of the emerging use of collecting X-ray diffraction data directly from the crystallization experiment. These in situ experiments are now routinely available to users at a number of synchrotron MX beamlines. A practical guide to the use of the method on the MX suite of beamlines at Diamond Light Source is given. PMID:25502203

Aller, Pierre; Sanchez-Weatherby, Juan; Foadi, James; Winter, Graeme; Lobley, Carina M C; Axford, Danny; Ashton, Alun W; Bellini, Domenico; Brandao-Neto, Jose; Culurgioni, Simone; Douangamath, Alice; Duman, Ramona; Evans, Gwyndaf; Fisher, Stuart; Flaig, Ralf; Hall, David R; Lukacik, Petra; Mazzorana, Marco; McAuley, Katherine E; Mykhaylyk, Vitaliy; Owen, Robin L; Paterson, Neil G; Romano, Pierpaolo; Sandy, James; Sorensen, Thomas; von Delft, Frank; Wagner, Armin; Warren, Anna; Williams, Mark; Stuart, David I; Walsh, Martin A

2015-01-01

303

Inactivation of recombinant human brain-type creatine kinase during denaturation by guanidine hydrochloride in a macromolecular crowding system.  

PubMed

In this study, we quantitatively examined the effects of the macromolecular crowding agents, polyethylene glycol 2000 (PEG 2000) and dextran 70, on guanidine hydrochloride (GdnHCl)-induced denaturation of recombinant human brain-type creatine kinase (rHBCK). Our results showed that both PEG 2000 and dextran 70 had a protective effect on the inactivation of rHBCK induced by 0.5 M GdnHCl at 25 °C. The presence of 200 g/L PEG 2000 resulted in the retention of 35.33 % of rHBCK activity after 4 h of inactivation, while no rHBCK activity was observed after denaturation in the absence of macromolecular crowding agents. The presence of PEG 2000 and dextran 70 at a concentration of 100 g/L could decelerate the k (2) value of the slow track to 21 and 33 %, respectively, in comparison to values obtained in the absence of crowding agents. Interestingly, inactivation of rHBCK in the presence of 200 g/L PEG 2000 followed first-order monophasic kinetics, with an apparent rate constant of 8?×?10(-5)?s(-1). The intrinsic fluorescence results showed that PEG 2000 was better than dextran 70 at stabilizing rHBCK conformation. In addition, the results of the phase diagram indicate that more intermediates may be captured when rHBCK is denatured in a macromolecular crowding system. Mixed crowding agents did not produce better results than single crowding agents, but the protective effects of PEG 2000 on the inactivation and unfolding of rHBCK tended to increase as the ratio of PEG 2000 increased in the mixed crowding agent solution. Though it is not clear which crowding agents more accurately simulated the intracellular environment, this study could lead to a better understanding of protein unfolding in the intracellular environment. PMID:23179281

Fan, Yong-Qiang; Liu, Hong-Jian; Li, Chang; Luan, Yu-Shi; Yang, Jun-Mo; Wang, Yu-Long

2013-01-01

304

The binding site of acetylcholine receptor: from synthetic peptides to solution and crystal structure.  

E-print Network

The binding site of acetylcholine receptor: from synthetic peptides to solution and crystal structure. Abstract: Our group has been employing short synthetic peptides, encompassing sequences from mimotope, with similar structural motifs to the AChR binding region, was selected by -bungarotoxin (-BTX

Kasher, Roni

305

Asymmetric Silver "Nanocarrot" Structures: Solution Synthesis and Their Asymmetric Plasmonic Resonances  

E-print Network

Asymmetric Silver "Nanocarrot" Structures: Solution Synthesis and Their Asymmetric Plasmonic the wet-chemical synthesis of asymmetric one-dimensional (1D) silver "nanocarrot" structures that exhibit of the longitudinal surface plasmon resonance peaks. The silver nanocarrots also show very high sensitivity

306

The NMR solution structure of human glutaredoxin in the fully reduced form1  

Microsoft Academic Search

The determination of the nuclear magnetic resonance (NMR) solution structure of fully reduced human glutaredoxin is described. A total of 1159 useful nuclear Overhauser effect (NOE) upper distance constraints and 187 dihedral angle constraints were obtained as the input for the structure calculations for which the torsion angle dynamics program DYANA has been utilized followed by energy minimization in water

Chaohong Sun; Marcelo J. Berardi; John H. Bushweller

1998-01-01

307

Structure Controlled Synthesis of Single-Walled Carbon Nanotubes Using Solution Based Catalyst Deposition  

E-print Network

Structure Controlled Synthesis of Single-Walled Carbon Nanotubes Using Solution Based Catalyst and physical properties, single-walled carbon nanotube (SWCNT) has been considered for many applications. We, mechanical application, etc. #12;Structure Controlled Synthesis of Carbon Nanotubes Theerapol Thurakitseree1

Mellor-Crummey, John

308

Structural characterization of human general transcription factor TFIIF in solution  

PubMed Central

Human general transcription factor IIF (TFIIF), a component of the transcription pre-initiation complex (PIC) associated with RNA polymerase II (Pol II), was characterized by size-exclusion chromatography (SEC), electrospray ionization mass spectrometry (ESI-MS), and chemical cross-linking. Recombinant TFIIF, composed of an equimolar ratio of ? and ? subunits, was bacterially expressed, purified to homogeneity, and found to have a transcription activity similar to a natural one in the human in vitro transcription system. SEC of purified TFIIF, as previously reported, suggested that this protein has a size >200 kDa. In contrast, ESI-MS of the purified sample gave a molecular size of 87 kDa, indicating that TFIIF is an ?? heterodimer, which was confirmed by matrix-assisted laser desorption/ionization (MALDI) MS of the cross-linked TFIIF components. Recent electron microscopy (EM) and photo-cross-linking studies showed that the yeast TFIIF homolog containing Tfg1 and Tfg2, corresponding to the human ? and ? subunits, exists as a heterodimer in the PIC, so the human TFIIF is also likely to exist as a heterodimer even in the PIC. In the yeast PIC, EM and photo-cross-linking studies showed different results for the mutual location of TFIIE and TFIIF along DNA. We have examined the direct interaction between human TFIIF and TFIIE by ESI-MS, SEC, and chemical cross-linking; however, no direct interaction was observed, at least in solution. This is consistent with the previous photo-cross-linking observation that TFIIF and TFIIE flank DNA separately on both sides of the Pol II central cleft in the yeast PIC. PMID:18218714

Akashi, Satoko; Nagakura, Shinjiro; Yamamoto, Seiji; Okuda, Masahiko; Ohkuma, Yoshiaki; Nishimura, Yoshifumi

2008-01-01

309

Receptor-bound conformation of cilengitide better represented by its solution-state structure than the solid-state structure.  

PubMed

The X-ray crystal and NMR spectroscopic structures of the peptide drug candidate Cilengitide (cyclo(RGDf(NMe)Val)) in various solvents are obtained and compared in addition to the integrin receptor bound conformation. The NMR-based solution structures exhibit conformations closely resembling the X-ray structure of Cilengitide bound to the head group of integrin ?v?3. In contrast, the structure of pure Cilengitide recrystallized from methanol reveals a different conformation controlled by the lattice forces of the crystal packing. Molecular modeling studies of the various ligand structures docked to the ?v?3 integrin revealed that utilization of the solid-state conformation of Cilengitide leads-unlike the solution-based structures-to a mismatch of the ligand-receptor interactions compared with the experimentally determined structure of the protein-ligand complex. Such discrepancies between solution and crystal conformations of ligands can be misleading during the structure-based lead optimization process and should thus be taken carefully into account in ligand orientated drug design. PMID:25251673

Marelli, Udaya Kiran; Frank, Andreas O; Wahl, Bernhard; La Pietra, Valeria; Novellino, Ettore; Marinelli, Luciana; Herdtweck, Eberhardt; Groll, Michael; Kessler, Horst

2014-10-27

310

Determination of domain structure of proteins from X-ray solution scattering.  

PubMed Central

An ab initio method for building structural models of proteins from x-ray solution scattering data is presented. Simulated annealing is employed to find a chain-compatible spatial distribution of dummy residues which fits the experimental scattering pattern up to a resolution of 0.5 nm. The efficiency of the method is illustrated by the ab initio reconstruction of models of several proteins, with known and unknown crystal structure, from experimental scattering data. The new method substantially improves the resolution and reliability of models derived from scattering data and makes solution scattering a useful technique in large-scale structural characterization of proteins. PMID:11371467

Svergun, D I; Petoukhov, M V; Koch, M H

2001-01-01

311

The NMR structure of cyclosporin A bound to cyclophilin in aqueous solution  

SciTech Connect

Cyclosporin A bound to the presumed receptor protein cyclophilin was studied in aqueous solution at pH 6.0 by nuclear magnetic resonance spectroscopy using uniform {sup 15}N- or {sup 13}C-labeling of cyclosporin A and heteronuclear spectral editing techniques. With an input of 108 intramolecular NOEs and four vicinal {sup 3}J{sub HN{alpha}} coupling constants, the three-dimensional structure of cyclosporin A bound to cyclophilin was calculated with the distance geometry program DISMAN, and the structures resulting from 181 converged calculations were energy refined with the program FANTOM. A group of 120 conformers was selected on the basis of the residual constraint violations and energy criteria to represent the solution structure. The average of the pairwise root-mean-square distances calculated for the backbone atoms of the 120 structures was 0.58 {angstrom}. The structure represents a novel conformation of cyclosporin A, for which the backbone conformation is significantly different from the previously reported structures in single crystals and in chloroform solution. The structure has all peptide bonds in the trans form, contains no elements of regular secondary structure and no intramolecular hydrogen bonds, and exposes nearly all polar groups to its environment. The root-mean-square distance between the backbone atoms of the crystal structure of cyclosporin A and the mean of the 120 conformers representing the NMR structure of cyclosporin A bound to cyclophilin is 2.5 {angstrom}.

Weber, C.; Wilder, G.; von Freyberg, B.; Braun, W.; Wuethrich, K. (Eidgenoessische Technische Hochschule-Hoenggerberg, Zuerich (Switzerland)); Traber, R.; Widmer, H. (Sandoz Pharma AG, Basel (Switzerland))

1991-07-02

312

Charge distribution and local structure of americium-bearing thorium oxide solid solutions.  

PubMed

The electronical and structural properties of Th(0.80)Am(0.20)O(2-x) materials have been studied by the coupling of X-ray diffraction and X-ray absorption spectroscopy techniques. A substoichiometric fluorite Th(IV)(0.80)Am(III)(0.20)O(1.90) solid solution is found following sintering in moisturized Ar-H(2). In contrast, heating of this sample in air leads to a nondefective fluorite Th(IV)(0.80)Am(IV)(0.20)O(2.00) solid solution. The structures of these solid solution compounds were fully characterized by assessing the interatomic distances, the coordination numbers, and the structural disorder. The effect of the sintering atmosphere on these crystallographical parameters and on the cation valences has been determined and the capability of ThO(2) to accommodate tri- and tetravalent actinides in the fluorite structure assessed. PMID:23072315

Carvajal-Nunez, U; Prieur, D; Vitova, T; Somers, J

2012-11-01

313

Solution structure and dynamics of GCN4 cognate DNA: NMR investigations  

Microsoft Academic Search

A 12 bp long GCN4-binding, self-complementary duplex DNA d(CATGACGTCATG)2 has been investigated by NMR spectroscopy to study the structure and dynamics of the molecule in aqueous solution. The NMR structure of the DNA obtained using simulated annealing and iterative relaxation matrix calculations compares quite closely with the X-ray structure of ATF\\/CREB DNA in complex with GCN4 protein (DNA-binding domain). The

Purnima Khandelwal; S. C. Panchal; P. K. Radha; R. V. Hosur

2001-01-01

314

FitEM2EM--tools for low resolution study of macromolecular assembly and dynamics.  

PubMed

Studies of the structure and dynamics of macromolecular assemblies often involve comparison of low resolution models obtained using different techniques such as electron microscopy or atomic force microscopy. We present new computational tools for comparing (matching) and docking of low resolution structures, based on shape complementarity. The matched or docked objects are represented by three dimensional grids where the value of each grid point depends on its position with regard to the interior, surface or exterior of the object. The grids are correlated using fast Fourier transformations producing either matches of related objects or docking models depending on the details of the grid representations. The procedures incorporate thickening and smoothing of the surfaces of the objects which effectively compensates for differences in the resolution of the matched/docked objects, circumventing the need for resolution modification. The presented matching tool FitEM2EMin successfully fitted electron microscopy structures obtained at different resolutions, different conformers of the same structure and partial structures, ranking correct matches at the top in every case. The differences between the grid representations of the matched objects can be used to study conformation differences or to characterize the size and shape of substructures. The presented low-to-low docking tool FitEM2EMout ranked the expected models at the top. PMID:18974836

Frankenstein, Ziv; Sperling, Joseph; Sperling, Ruth; Eisenstein, Miriam

2008-01-01

315

Local structures of mechanically alloyed Fe100-xCux solid solutions studied by X-ray absorption fine structure.  

PubMed

The local structures of the immiscible Fe(100-x)Cu(x) alloys (x= 0, 10, 20, 40, 60, 80 and 100) produced by mechanical alloying have been investigated by XAFS. For the Fe(100-x)Cu(x) (x > or = 40) solid solutions, the local structures around Fe atoms change from bcc structure to fcc one and the Cu atoms maintain the original coordination geometry after milling for 160 hours. On the contrary, the local structures around Cu atoms in both of Fe80Cu20 and Fe90Cu10 alloys appear a transition from fcc to bcc structure. We found that the Debye-waller factor sigma of fcc Fe-Cu phase is larger than that of bcc Fe-Cu phase, and the sigma (0.099 A) around Fe atoms is larger than that (0.089 A) of Cu in the Fe(100-x)Cu(x) (x > or = 40) solid solutions. This suggests that the mechanically alloyed Fe(100-x)Cu(x) supersaturated solid solution is not a homogeneous alloy, and consists of Fe-rich and Cu-rich regions for various compositions. A possible mechanism for bcc-to-fcc and fcc-to-bcc changes in Fe(100-x)Cu(x) solid solutions is discussed in relation to the interdiffusion and transition induced by the ball milling. PMID:11512926

Wei, S; Yan, W; Fan, J; Li, Y; Liu, W; Wang, X

2001-03-01

316

In situ structural characterization of ferric iron dimers in aqueous solutions: identification of ?-oxo species.  

PubMed

The structure of ferric iron (Fe(3+)) dimers in aqueous solutions has long been debated. In this work, we have determined the dimer structure in situ in aqueous solutions using extended X-ray absorption fine structure (EXAFS) spectroscopy. An Fe K-edge EXAFS analysis of 0.2 M ferric nitrate solutions at pH 1.28-1.81 identified a Fe-Fe distance at ?3.6 Å, strongly indicating that the dimers take the ?-oxo form. The EXAFS analysis also indicates two short Fe-O bonds at ?1.80 Å and ten long Fe-O bonds at ?2.08 Å, consistent with the ?-oxo dimer structure. The scattering from the Fe-Fe paths interferes destructively with that from paths belonging to Fe(OH2)6(3+) monomers that coexist with the dimers, leading to a less apparent Fe shell in the EXAFS Fourier transform. This might be a reason why the characteristic Fe-Fe distance was not detected in previous EXAFS studies. The existence of ?-oxo dimers is further confirmed by Mössbauer analyses of analogous quick frozen solutions. This work also explores the electronic structure and the relative stability of the ?-oxo dimer in a comparison to the dihydroxo dimer using density function theory (DFT) calculations. The identification of such dimers in aqueous solutions has important implications for iron (bio)inorganic chemistry and geochemistry, such as understanding the formation mechanisms of Fe oxyhydroxides at molecular scale. PMID:23701439

Zhu, Mengqiang; Puls, Brendan W; Frandsen, Cathrine; Kubicki, James D; Zhang, Hengzhong; Waychunas, Glenn A

2013-06-17

317

About Small Streams and Shiny Rocks: Macromolecular Crystal Growth in Microfluidics  

NASA Technical Reports Server (NTRS)

We are developing a novel technique with which we have grown diffraction quality protein crystals in very small volumes, utilizing chip-based, microfluidic ("LabChip") technology. With this technology volumes smaller than achievable with any laboratory pipette can be dispensed with high accuracy. We have performed a feasibility study in which we crystallized several proteins with the aid of a LabChip device. The protein crystals are of excellent quality as shown by X-ray diffraction. The advantages of this new technology include improved accuracy of dispensing for small volumes, complete mixing of solution constituents without bubble formation, highly repeatable recipe and growth condition replication, and easy automation of the method. We have designed a first LabChip device specifically for protein crystallization in batch mode and can reliably dispense and mix from a range of solution constituents. We are currently testing this design. Upon completion additional crystallization techniques, such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility aboard the International Space Station.

vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

2002-01-01

318

Improved reproducibility of unit-cell parameters in macromolecular cryocrystallography by limiting dehydration during crystal mounting  

PubMed Central

In macromolecular cryocrystallography unit-cell parameters can have low reproducibility, limiting the effectiveness of combining data sets from multiple crystals and inhibiting the development of defined repeatable cooling protocols. Here, potential sources of unit-cell variation are investigated and crystal dehydration during loop-mounting is found to be an important factor. The amount of water lost by the unit cell depends on the crystal size, the loop size, the ambient relative humidity and the transfer distance to the cooling medium. To limit water loss during crystal mounting, a threefold strategy has been implemented. Firstly, crystal manipulations are performed in a humid environment similar to the humidity of the crystal-growth or soaking solution. Secondly, the looped crystal is transferred to a vial containing a small amount of the crystal soaking solution. Upon loop transfer, the vial is sealed, which allows transport of the crystal at its equilibrated humidity. Thirdly, the crystal loop is directly mounted from the vial into the cold gas stream. This strategy minimizes the exposure of the crystal to relatively low humidity ambient air, improves the reproducibility of low-temperature unit-cell parameters and offers some new approaches to crystal handling and cryoprotection. PMID:25084331

Farley, Christopher; Burks, Geoffry; Siegert, Thomas; Juers, Douglas H.

2014-01-01

319

Structure and properties of loaded silica contacts during pressure solution: impedance spectroscopy measurements under hydrothermal conditions  

Microsoft Academic Search

In order to investigate directly the structure and properties of grain boundaries in silicate materials undergoing pressure\\u000a solution, in situ measurements of these properties are required. We report electrical impedance spectroscopy measurements,\\u000a performed, under hydrothermal conditions, on individual glass–glass and glass-quartz contacts undergoing pressure solution.\\u000a Resulting estimates of the average grain boundary diffusivity product ($$ Z = D\\\\delta_{\\\\text{av}} C^{*} $$)

R. van Noort; C. J. Spiers; C. J. Peach

2011-01-01

320

Structure and Dynamics in Aqueous Solutions of Amphiphilic Sodium Maleate-Containing Alternating Copolymers  

Microsoft Academic Search

The structure of aqueous solutions of sodium maleate copolymers with comonomers of variable hydrophobicity are examined using a combination of small-angle neutron scattering, small-angle X-ray scattering, and rheometry. Semidilute solutions of the copolymers made with mildly hydrophobic comonomers exhibit scattering and rheology that are typical of flexible polyelectrolytes, with a correlation length scaling with polymer concentration as c-R with R)

E. Di Cola; N. Plucktaveesak; T. A. Waigh; R. H. Colby; J. S. Tan; W. Pyckhout-Hintzen; R. K. Heenan

2004-01-01

321

Solution and Adsorbed-State Structural Ensembles Predicted for the Statherin-Hydroxyapatite System  

Microsoft Academic Search

We have developed a multiscale structure prediction technique to study solution- and adsorbed-state ensembles of biomineralization proteins. The algorithm employs a Metropolis Monte Carlo-plus-minimization strategy that varies all torsional and rigid-body protein degrees of freedom. We applied the technique to fold statherin, starting from a fully extended peptide chain in solution, in the presence of hydroxyapatite (HAp) (001), (010), and

David L. Masica; Jeffrey J. Gray

2009-01-01

322

Solution- and Adsorbed-State Structural Ensembles Predicted for the Statherin-Hydroxyapatite System  

PubMed Central

Abstract We have developed a multiscale structure prediction technique to study solution- and adsorbed-state ensembles of biomineralization proteins. The algorithm employs a Metropolis Monte Carlo-plus-minimization strategy that varies all torsional and rigid-body protein degrees of freedom. We applied the technique to fold statherin, starting from a fully extended peptide chain in solution, in the presence of hydroxyapatite (HAp) (001), (010), and (100) monoclinic crystals. Blind (unbiased) predictions capture experimentally observed macroscopic and high-resolution structural features and show minimal statherin structural change upon adsorption. The dominant structural difference between solution and adsorbed states is an experimentally observed folding event in statherin's helical binding domain. Whereas predicted statherin conformers vary slightly at three different HAp crystal faces, geometric and chemical similarities of the surfaces allow structurally promiscuous binding. Finally, we compare blind predictions with those obtained from simulation biased to satisfy all previously published solid-state NMR (ssNMR) distance and angle measurements (acquired from HAp-adsorbed statherin). Atomic clashes in these structures suggest a plausible, alternative interpretation of some ssNMR measurements as intermolecular rather than intramolecular. This work demonstrates that a combination of ssNMR and structure prediction could effectively determine high-resolution protein structures at biomineral interfaces. PMID:19383454

Masica, David L.; Gray, Jeffrey J.

2009-01-01

323

Ice crystallization in ultrafine water-salt aerosols: nucleation, ice-solution equilibrium, and internal structure.  

PubMed

Atmospheric aerosols have a strong influence on Earth's climate. Elucidating the physical state and internal structure of atmospheric aqueous aerosols is essential to predict their gas and water uptake, and the locus and rate of atmospherically important heterogeneous reactions. Ultrafine aerosols with sizes between 3 and 15 nm have been detected in large numbers in the troposphere and tropopause. Nanoscopic aerosols arising from bubble bursting of natural and artificial seawater have been identified in laboratory and field experiments. The internal structure and phase state of these aerosols, however, cannot yet be determined in experiments. Here we use molecular simulations to investigate the phase behavior and internal structure of liquid, vitrified, and crystallized water-salt ultrafine aerosols with radii from 2.5 to 9.5 nm and with up to 10% moles of ions. We find that both ice crystallization and vitrification of the nanodroplets lead to demixing of pure water from the solutions. Vitrification of aqueous nanodroplets yields nanodomains of pure low-density amorphous ice in coexistence with vitrified solute rich aqueous glass. The melting temperature of ice in the aerosols decreases monotonically with an increase of solute fraction and decrease of radius. The simulations reveal that nucleation of ice occurs homogeneously at the subsurface of the water-salt nanoparticles. Subsequent ice growth yields phase-segregated, internally mixed, aerosols with two phases in equilibrium: a concentrated water-salt amorphous mixture and a spherical cap-like ice nanophase. The surface of the crystallized aerosols is heterogeneous, with ice and solution exposed to the vapor. Free energy calculations indicate that as the concentration of salt in the particles, the advance of the crystallization, or the size of the particles increase, the stability of the spherical cap structure increases with respect to the alternative structure in which a core of ice is fully surrounded by solution. We predict that micrometer-sized particles and nanoparticles have the same equilibrium internal structure. The variation of liquid-vapor surface tension with solute concentration is a key factor in determining whether a solution-embedded ice core or vapor-exposed ice cap is the equilibrium structure of the aerosols. In agreement with experiments, we predict that the structure of mixed-phase HNO3-water particles, representative of polar stratospheric clouds, consists of an ice core surrounded by freeze-concentrated solution. The results of this work are important to determine the phase state and internal structure of sea spray ultrafine aerosols and other mixed-phase particles under atmospherically relevant conditions. PMID:24820354

Hudait, Arpa; Molinero, Valeria

2014-06-01

324

Stability of the grain structure in 2219-O aluminum alloy friction stir welds during solution treatment  

SciTech Connect

The stability of the grain structure in 2219-O aluminum alloy friction stir welds during solution treatment has been investigated. Experimental results show that the solution treatment causes drastic grain growth, Grain growth initiates at the surface and the bottom of the weld and then extends to the weld centre within several minutes. The solution treatment temperature and the welding heat input have a significant effect on grain growth. The higher the solution temperature, or the higher the welding heat input, the greater the grain growth. The instability of the grains is attributed to an imbalance between thermodynamic driving forces for grain growth and the pinning forces impeding grain boundary migration during solution treatment.

Chen, Y.C. [National Key Laboratory of Precision Hot Processing of Metals, Harbin Institute of Technology, Harbin 150001 (China) and National Key Laboratory of Advanced Welding Production Technology, Harbin Institute of Technology, Harbin 150001 (China)]. E-mail: armstrong@hit.edu.cn; Feng, J.C. [National Key Laboratory of Advanced Welding Production Technology, Harbin Institute of Technology, Harbin 150001 (China); Liu, H.J. [National Key Laboratory of Advanced Welding Production Technology, Harbin Institute of Technology, Harbin 150001 (China)

2007-02-15

325

Patchy worm-like micelles: solution structure studied by small-angle neutron scattering.  

PubMed

Triblock terpolymers exhibit a rich self-organization behavior including the formation of fascinating cylindrical core-shell structures with a phase separated corona. After crystallization-induced self-assembly of polystyrene-block-polyethylene-block-poly(methyl methacrylate) triblock terpolymers (abbreviated as SEMs = Styrene-Ethylene-Methacrylates) from solution, worm-like core-shell micelles with a patchy corona of polystyrene and poly(methyl methacrylate) were observed by transmission electron microscopy. However, the solution structure is still a matter of debate. Here, we present a method to distinguish in situ between a Janus-type (two faced) and a patchy (multiple compartments) configuration of the corona. To discriminate between both models the scattering intensity must be determined mainly by one corona compartment. Contrast variation in small-angle neutron scattering enables us to focus on one compartment of the worm-like micelles. The results validate the existence of the patchy structure also in solution. PMID:22880203

Rosenfeldt, Sabine; Lüdel, Frank; Schulreich, Christoph; Hellweg, Thomas; Radulescu, Aurel; Schmelz, Joachim; Schmalz, Holger; Harnau, Ludger

2012-10-01

326

Patchy worm-like micelles: solution structure studied by small-angle neutron scattering  

E-print Network

Triblock terpolymers exhibit a rich self-organization behavior including the formation of fascinating cylindrical core-shell structures with a phase separated corona. After crystallization-induced self-assembly of polystryrene-(block)-polyethylene-(block)-poly(methyl methacrylate) triblock terpolymers (abbreviated as SEMs = Styrene-Ethylene-Methacrylates) from solution, worm-like core-shell micelles with a patchy corona of polystryrene and poly(methyl methacrylate) were observed by transmission electron microscopy. However, the solution structure is still a matter of debate. Here, we present a method to distinguish in-situ between a Janus-type (two faced) and a patchy (multiple compartments) configuration of the corona. To discriminate between both models the scattering intensity must be determined mainly by one corona compartment. Contrast variation in small-angle neutron scattering enables us to focus on one compartment of the SEMs. The results validate the existence of the patchy structure also in solution.

S. Rosenfeldt; F. Luedel; C. Schulreich; T. Hellweg; A. Radulescu; J. Schmelz; H. Schmalz; L. Harnau

2012-09-20

327

Mathieu function solutions for photoacoustic waves in sinusoidal one-dimensional structures  

NASA Astrophysics Data System (ADS)

The photoacoustic effect for a one-dimensional structure, the sound speed of which varies sinusoidally in space, is shown to be governed by an inhomogeneous Mathieu equation with the forcing term dependent on the spatial and temporal properties of the exciting optical radiation. New orthogonality relations, traveling wave Mathieu functions, and solutions to the inhomogeneous Mathieu equation are found, which are used to determine the character of photoacoustic waves in infinite and finite length phononic structures. Floquet solutions to the Mathieu equation give the positions of the band gaps, the damping of the acoustic waves within the band gaps, and the dispersion relation for photoacoustic waves. The solutions to the Mathieu equation give the photoacoustic response of the structure, show the space equivalent of subharmonic generation and acoustic confinement when waves are excited within band gaps.

Wu, Binbin; Diebold, Gerald J.

2012-07-01

328

Mathieu function solutions for photoacoustic waves in sinusoidal one-dimensional structures.  

PubMed

The photoacoustic effect for a one-dimensional structure, the sound speed of which varies sinusoidally in space, is shown to be governed by an inhomogeneous Mathieu equation with the forcing term dependent on the spatial and temporal properties of the exciting optical radiation. New orthogonality relations, traveling wave Mathieu functions, and solutions to the inhomogeneous Mathieu equation are found, which are used to determine the character of photoacoustic waves in infinite and finite length phononic structures. Floquet solutions to the Mathieu equation give the positions of the band gaps, the damping of the acoustic waves within the band gaps, and the dispersion relation for photoacoustic waves. The solutions to the Mathieu equation give the photoacoustic response of the structure, show the space equivalent of subharmonic generation and acoustic confinement when waves are excited within band gaps. PMID:23005556

Wu, Binbin; Diebold, Gerald J

2012-07-01

329

On the origin of mesoscale structures in aqueous solutions of tertiary butyl alcohol: the mystery resolved.  

PubMed

We have performed a detailed experimental study on aqueous solutions of tertiary butyl alcohol which were a subject of long-standing controversies regarding the puzzling presence of virtually infinitely stable large-scale structures in such solutions occurring at length scales exceeding appreciably dimensions of individual molecules, referred to also as mesoscale structures. A combination of static and dynamic light scattering yielding information on solution structure and dynamics and gas chromatography coupled with mass spectrometry yielding information on chemical composition was used. We show that tertiary butyl alcohol clearly exhibiting such structures upon mixing with water does not contain any propylene oxide, which was previously considered as a source of these structures (an impurity expected to be present in all commercial samples of TBA). More importantly, we show that no mesoscale structures are generated upon addition of propylene oxide to aqueous solutions of TBA. The ternary system TBA/water/propylene oxide exhibits homogeneous mixing of the components on mesoscales. We show that the source of the mesoscale structures is a mesophase separation of appreciably more hydrophobic compounds than propylene oxide. These substances are explicitly analytically identified as well as their disappearance upon filtering out the mesoscale structures by nanopore filtration. We clearly show which substances are disappearing upon filtration and which are not. This enables us to estimate with rather high probability the chemical composition of the mesoscale structures. Visualization of large-scale structures via nanoparticle tracking analysis is also presented. Video capturing the mesoscale particles as well as their Brownian motion can be found in the Supporting Information . PMID:24559045

Sedlák, Marián; Rak, Dmytro

2014-03-13

330

MgAgAs structure type solid solutions as a new thermoelectric material  

Microsoft Academic Search

Solid solutions TiNiSn1-xMe'x (Me'=Al,Sb,Bi) and ZrNi1-xMe''xSn (Me''=Cr,Mn,Cu) with MgAgAs structure type were obtained on the basis of the TiNiSn and ZrNiSn semiconducting compounds. X-ray analysis was used to define the stability range of the solid solutions. The temperature dependence of the resistivity and thermopower showed a loss of semiconducting properties. The sign of thermopower remains negative for all solid solutions

L. P. Romaka; Yu. V. Stadnyk; A. M. Goryn; Yu. K. Gorelenko; R. V. Skolozdra

1997-01-01

331

An efficient closed-form solution for acoustic emission source location in three-dimensional structures  

SciTech Connect

This paper presents an efficient closed-form solution (ECS) for acoustic emission(AE) source location in three-dimensional structures using time difference of arrival (TDOA) measurements from N receivers, N ? 6. The nonlinear location equations of TDOA are simplified to linear equations. The unique analytical solution of AE sources for unknown velocity system is obtained by solving the linear equations. The proposed ECS method successfully solved the problems of location errors resulting from measured deviations of velocity as well as the existence and multiplicity of solutions induced by calculations of square roots in existed close-form methods.

Li, Xibing [School of Resources and Safety Engineering, Central South University, Changsha, 410083 (China)] [School of Resources and Safety Engineering, Central South University, Changsha, 410083 (China); Dong, Longjun, E-mail: csudlj@163.com [School of Resources and Safety Engineering, Central South University, Changsha, 410083 (China) [School of Resources and Safety Engineering, Central South University, Changsha, 410083 (China); Australian Centre for Geomechanics, The University of Western Australia, Crawley, 6009 (Australia)

2014-02-15

332

The Effect of Cholesterol on the Solution Structure of Proteins of Photosystem II. Protein Secondary Structure and  

E-print Network

The Effect of Cholesterol on the Solution Structure of Proteins of Photosystem II. Protein, 1998 Cholesterol induces large perturbations in the physical proper- ties of membranes, especially at physiological temperatures. This study was designed to examine the interaction of cholesterol with lipid

Carpentier, Robert

333

Macromolecular therapeutics in cancer treatment: the EPR effect and beyond.  

PubMed

In this review, I have discussed various issues of the cancer drug targeting primarily related to the EPR (enhanced permeability and retention) effect, which utilized nanomedicine or macromolecular drugs. The content goes back to the development of the first polymer-protein conjugate anticancer agent SMANCS and development of the arterial infusion in Lipiodol formulation into the tumor feeding artery (hepatic artery for hepatoma). The brief account on the EPR effect and its definition, factors involved, heterogeneity, and various methods of augmentation of the EPR effect, which showed remarkably improved clinical outcomes are also discussed. Various obstacles involved in drug developments and commercialization are also discussed through my personal experience and recollections. PMID:22595146

Maeda, Hiroshi

2012-12-10

334

On macromolecular refinement at subatomic resolution withinteratomic scatterers  

SciTech Connect

A study of the accurate electron density distribution in molecular crystals at subatomic resolution, better than {approx} 1.0 {angstrom}, requires more detailed models than those based on independent spherical atoms. A tool conventionally used in small-molecule crystallography is the multipolar model. Even at upper resolution limits of 0.8-1.0 {angstrom}, the number of experimental data is insufficient for the full multipolar model refinement. As an alternative, a simpler model composed of conventional independent spherical atoms augmented by additional scatterers to model bonding effects has been proposed. Refinement of these mixed models for several benchmark datasets gave results comparable in quality with results of multipolar refinement and superior of those for conventional models. Applications to several datasets of both small- and macro-molecules are shown. These refinements were performed using the general-purpose macromolecular refinement module phenix.refine of the PHENIX package.

Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.; Lunin, Vladimir Y.; Urzhumtsev, Alexandre

2007-11-09

335

Size-exclusion chromatography system for macromolecular interaction analysis  

DOEpatents

A low pressure, microcomputer controlled system employing high performance liquid chromatography (HPLC) allows for precise analysis of the interaction of two reversibly associating macromolecules such as proteins. Since a macromolecular complex migrates faster than its components during size-exclusion chromatography, the difference between the elution profile of a mixture of two macromolecules and the summation of the elution profiles of the two components provides a quantifiable indication of the degree of molecular interaction. This delta profile is used to qualitatively reveal the presence or absence of significant interaction or to rank the relative degree of interaction in comparing samples and, in combination with a computer simulation, is further used to quantify the magnitude of the interaction in an arrangement wherein a microcomputer is coupled to analytical instrumentation in a novel manner.

Stevens, Fred J. (Downers Grove, IL)

1988-01-01

336

Macromolecular crystal growth experiments on International Microgravity Laboratory--1.  

PubMed Central

Macromolecular crystal growth experiments, using satellite tobacco mosaic virus (STMV) and canavalin from jack beans as samples, were conducted on a US Space Shuttle mission designated International Microgravity Laboratory--1 (IML-1), flown January 22-29, 1992. Parallel experiments using identical samples were carried out in both a vapor diffusion-based device (PCG) and a liquid-liquid diffusion-based instrument (CRYOSTAT). The experiments in each device were run at 20-22 degrees C and at colder temperatures. Crystals were grown in virtually every trial, but the characteristics of the crystals were highly dependent on the crystallization technique employed and the temperature experience of the sample. In general, very good results, based on visual inspection of the crystals, were obtained in both PCG and CRYOSTAT. Unusually impressive results were, however, achieved for STMV in the CRYOSTAT instrument. STMV crystals grown in microgravity by liquid-liquid diffusion were more than 10-fold greater in total volume than any STMV crystals previously grown in the laboratory. X-ray diffraction data collected from eight STMV crystals grown in CRYOSTAT demonstrated a substantial improvement in diffraction quality over the entire resolution range when compared to data from crystals grown on Earth. In addition, the extent of the diffraction pattern for the STMV crystals grown in space extended to 1.8 A resolution, whereas the best crystals that were ever grown under conditions of Earth's gravity produced data limited to 2.3 A resolution. Other observations indicate that the growth of macromolecular crystals is indeed influenced by the presence or absence of gravity. These observations further suggest, consistent with earlier results, that the elimination of gravity provides a more favorable environment for such processes. PMID:1303744

Day, J.; McPherson, A.

1992-01-01

337

Structure solution of DNA-binding proteins and complexes with ARCIMBOLDO libraries  

PubMed Central

Protein–DNA interactions play a major role in all aspects of genetic activity within an organism, such as transcription, packaging, rearrangement, replication and repair. The molecular detail of protein–DNA interactions can be best visualized through crystallography, and structures emphasizing insight into the principles of binding and base-sequence recognition are essential to understanding the subtleties of the underlying mechanisms. An increasing number of high-quality DNA-binding protein structure determinations have been witnessed despite the fact that the crystallographic particularities of nucleic acids tend to pose specific challenges to methods primarily developed for proteins. Crystallographic structure solution of protein–DNA complexes therefore remains a challenging area that is in need of optimized experimental and computational methods. The potential of the structure-solution program ARCIMBOLDO for the solution of protein–DNA complexes has therefore been assessed. The method is based on the combination of locating small, very accurate fragments using the program Phaser and density modification with the program SHELXE. Whereas for typical proteins main-chain ?-helices provide the ideal, almost ubiquitous, small fragments to start searches, in the case of DNA complexes the binding motifs and DNA double helix constitute suitable search fragments. The aim of this work is to provide an effective library of search fragments as well as to determine the optimal ARCIMBOLDO strategy for the solution of this class of structures. PMID:24914984

Pröpper, Kevin; Meindl, Kathrin; Sammito, Massimo; Dittrich, Birger; Sheldrick, George M.; Pohl, Ehmke; Usón, Isabel

2014-01-01

338

Discovering Free Energy Basins for Macromolecular Systems via Guided Multiscale Simulation  

PubMed Central

An approach for the automated discovery of low free energy states of macromolecular systems is presented. The method does not involve delineating the entire free energy landscape but proceeds in a sequential free energy minimizing state discovery, i.e., it first discovers one low free energy state and then automatically seeks a distinct neighboring one. These states and the associated ensembles of atomistic configurations are characterized by coarse-grained variables capturing the large-scale structure of the system. A key facet of our approach is the identification of such coarse-grained variables. Evolution of these variables is governed by Langevin dynamics driven by thermal-average forces and mediated by diffusivities, both of which are constructed by an ensemble of short molecular dynamics runs. In the present approach, the thermal-average forces are modified to account for the entropy changes following from our knowledge of the free energy basins already discovered. Such forces guide the system away from the known free energy minima, over free energy barriers, and to a new one. The theory is demonstrated for lactoferrin, known to have multiple energy-minimizing structures. The approach is validated using experimental structures and traditional molecular dynamics. The method can be generalized to enable the interpretation of nanocharacterization data (e.g., ion mobility – mass spectrometry, atomic force microscopy, chemical labeling, and nanopore measurements). PMID:22423635

Sereda, Yuriy V.; Singharoy, Abhishek B.; Jarrold, Martin F.; Ortoleva, Peter J.

2012-01-01

339

Distinct Contribution of Electrostatics, Initial Conformational Ensemble, and Macromolecular Stability in RNA Folding  

SciTech Connect

We distinguish the contribution of the electrostatic environment, initial conformational ensemble, and macromolecular stability on the folding mechanism of a large RNA using a combination of time-resolved 'Fast Fenton' hydroxyl radical footprinting and exhaustive kinetic modeling. This integrated approach allows us to define the folding landscape of the L-21 Tetrahymena thermophila group I intron structurally and kinetically from its earliest steps with unprecedented accuracy. Distinct parallel pathways leading the RNA to its native form upon its Mg2+-induced folding are observed. The structures of the intermediates populating the pathways are not affected by variation of the concentration and type of background monovalent ions (electrostatic environment) but are altered by a mutation that destabilizes one domain of the ribozyme. Experiments starting from different conformational ensembles but folding under identical conditions show that whereas the electrostatic environment modulates molecular flux through different pathways, the initial conformational ensemble determines the partitioning of the flux. This study showcases a robust approach for the development of kinetic models from collections of local structural probes.

Laederach,A.; Shcherbakova, I.; Jonikas, M.; Altman, R.; Brenowitz, M.

2007-01-01

340

Data structures for the distributed iterative solution of non-conventional finite element models  

Microsoft Academic Search

A class of specialised data structures designed for the distributed solution of non-conventional finite element formulations, which are equally effective when used in conjunction with conventional formulations, is presented. We begin by briefly discussing how the non-con- ventional finite element formulations being developed within the structural analysis group at IST (Freitas JAT, Almeida JPM, Pereira EMBR. Non-conventional formulations for the

Ildi Cismasiu; J. P. Moitinho De Almeida

2007-01-01

341

Structural Properties of High and Low Density Water in a Supercooled Aqueous Solution of Salt  

E-print Network

We consider and compare the structural properties of bulk TIP4P water and of a sodium chloride aqueous solution in TIP4P water with concentration c = 0.67 mol/kg, in the metastable supercooled region. In a previous paper [D. Corradini, M. Rovere and P. Gallo, J. Chem. Phys. 132, 134508 (2010)] we found in both systems the presence of a liquid-liquid critical point (LLCP). The LLCP is believed to be the end point of the coexistence line between a high density liquid (HDL) and a low density liquid (LDL) phase of water. In the present paper we study the different features of water-water structure in HDL and LDL both in bulk water and in the solution. We find that the ions are able to modify the bulk LDL structure, rendering water-water structure more similar to the bulk HDL case. By the study of the hydration structure in HDL and LDL, a possible mechanism for the modification of the bulk LDL structure in the solution is identified in the substitution of the oxygen by the chloride ion in oxygen coordination shells.

D. Corradini; M. Rovere; P. Gallo

2011-01-27

342

Solution quenched structure of wrought PH 13–8 Mo stainless steel  

Microsoft Academic Search

The solution-quenched structure of wrought PH13-8Mo steel was investigated by transmission electron microscope (TEM) and small-angle neutron scattering (SANS). Retained austenite and primary carbide were observed in the TEM. SANS measurements indicated microstructural inhomogeneities, comprising carbides and atom-clusters of elements having small scattering length, such as, Al, Si, S and P.

J. Mittra; G. K. Dey; D. Sen; A. K. Patra; S. Mazumder; P. K. De

2004-01-01

343

Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX autosol wizard  

SciTech Connect

Ten measures of experimental electron-density-map quality are examined and the skewness of electron density is found to be the best indicator of actual map quality. A Bayesian approach to estimating map quality is developed and used in the PHENIX AutoSol wizard to make decisions during automated structure solution.

Terwilliger, Thomas C [Los Alamos National Laboratory; Adams, Paul D [LBNL; Read, Randy J [UNIV OF CAMBRIDGE; Mccoy, Airlie J [UNIV OF CAMBRIDGE

2008-01-01

344

Parallel-vector solution of large-scale structural analysis problems on supercomputers  

NASA Technical Reports Server (NTRS)

A direct linear equation solution method based on the Choleski factorization procedure is presented which exploits both parallel and vector features of supercomputers. The new equation solver is described, and its performance is evaluated by solving structural analysis problems on three high-performance computers. The method has been implemented using Force, a generic parallel FORTRAN language.

Storaasli, Olaf O.; Nguyen, Duc T.; Agarwal, Tarun K.

1989-01-01

345

Supramolecular porphyrinic prisms: coordinative assembly and solution phase X-ray structural characterization{  

E-print Network

Supramolecular porphyrinic prisms: coordinative assembly and solution phase X-ray structural 2006 DOI: 10.1039/b610025b Supramolecular porphyrin prisms have been obtained via coordinative self on the formation of well defined prism-shaped assemblies featuring three, six, or nine porphyrins and comprising

346

Lithium Diisopropylamide Solvated by Monodentate and Bidentate Ligands: Solution Structures and Ligand Binding  

E-print Network

Lithium Diisopropylamide Solvated by Monodentate and Bidentate Ligands: Solution Structures, 1997X Abstract: 6Li and 15N NMR spectroscopic studies of lithium diisopropylamide ([6Li]LDA and [6Li,15 are correlated with those obtained previously for lithium hexamethyldisilazide. Introduction Despite

Collum, David B.

347

Protein folding, protein structure and the origin of life: Theoretical methods and solutions of dynamical problems  

NASA Technical Reports Server (NTRS)

Theoretical methods and solutions of the dynamics of protein folding, protein aggregation, protein structure, and the origin of life are discussed. The elements of a dynamic model representing the initial stages of protein folding are presented. The calculation and experimental determination of the model parameters are discussed. The use of computer simulation for modeling protein folding is considered.

Weaver, D. L.

1982-01-01

348

The hydration structure of guanidinium and thiocyanate ions: Implications for protein stability in aqueous solution  

Microsoft Academic Search

Neutron diffraction experiments were carried out on aqueous solutions containing either guanidinium or thiocyanate ions. The first-order difference method of neutron diffraction and isotopic substitution was applied, and the hydration structures of two of nature's strongest denaturant ions were determined. Each ion is shown to interact weakly with water: Guanidinium has no recognizable hydration shell and is one of the

P. E. Mason; G. W. Neilson; C. E. Dempsey; A. C. Barnes; J. M. Cruickshank

2003-01-01

349

Solution Structure of the CBM10 Cellulose Binding Module from Pseudomonas Xylanase A,  

E-print Network

Solution Structure of the CBM10 Cellulose Binding Module from Pseudomonas Xylanase A, S. Raghothama), whose common function is to attach the enzyme to the polymeric substrate. Xylanase A from Pseudomonas), many xylanases contain domains that bind specifically to cellulose rather than xylan (5). It has been

Williamson, Mike P.

350

Pressure-dependent Changes in the Solution Structure of Hen Egg-white Lysozyme  

E-print Network

Pressure-dependent Changes in the Solution Structure of Hen Egg-white Lysozyme Mohamed Refaee1 conditions, because these clarify the physical constraints on pro- teins. One obvious extreme is pressure, but so far little is known of the behavior of proteins under pressure, largely for technical reasons. We

Williamson, Mike P.

351

First-principles study of ternary fcc solution phases from special quasirandom structures  

SciTech Connect

In the present work, ternary special quasirandom structures (SQSs) for a fcc solid solution phase are generated at different compositions, x{sub A}=x{sub B}=x{sub C}=(1/3) and x{sub A}=(1/2), x{sub B}=x{sub C}=(1/4), whose correlation functions are satisfactorily close to those of a random fcc solution. The generated SQSs are used to calculate the mixing enthalpy of the fcc phase in the Ca-Sr-Yb system. It is observed that first-principles calculations of all the binary and ternary SQSs in the Ca-Sr-Yb system exhibit very small local relaxation. It is concluded that the fcc ternary SQSs can provide valuable information about the mixing behavior of the fcc ternary solid solution phase. The SQSs presented in this work can be widely used to study the behavior of ternary fcc solid solutions.

Shin Dongwon; Wang Yi; Liu Zikui [Department of Materials Science and Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802 (United States); Walle, Axel van de [Engineering and Applied Science Division, California Institute of Technology, Pasadena, California 91125 (United States)

2007-10-01

352

Liquid-Structure Forces and Electrostatic Modulation of Biomolecular Interactions in Solution  

PubMed Central

Molecular interactions in solution are controlled by the bulk medium and by the forces originating in the structured region of the solvent close to the solutes. In this paper, a model of electrostatic and liquid-structure forces for dynamics simulations of biomolecules is presented. The model introduces information on the microscopic nature of the liquid in the vicinity of polar and charged groups and the associated non-pairwise character of the forces, thus improving upon conventional continuum representations. The solvent is treated as a polar and polarizable medium, with dielectric properties described by an inhomogeneous version of the Onsager theory. This treatment leads to an effective position-dependent dielectric permittivity that incorporates saturation effects of the electric field and the spatial variation of the liquid density. The non-pairwise additivity of the liquid-structure forces is represented by centers of force located at specific points in the liquid phase. These out-of-the-solute centers are positioned at the peaks of liquid density and exert local, external forces on the atoms of the solute. The density is calculated from a barometric law, using a Lennard-Jones-type solute–liquid effective interaction potential. The conceptual aspects of the model and its exact numerical solutions are discussed for single alkali and halide ions and for ion-pair interactions. The practical aspects of the model and the simplifications introduced for efficient computation of forces in molecular solutes are discussed in the context of polar and charged amino acid dimers. The model reproduces the contact and solvent-separated minima and the desolvation barriers of intermolecular potentials of mean force of amino acid dimers, as observed in atomistic dynamics simulations. Possible refinements based on an improved treatment of molecular correlations are discussed. PMID:17201447

Hassan, Sergio A.

2008-01-01

353

Solution Structure and Dynamics of Human Hemoglobin in the Carbonmonoxy Form  

PubMed Central

The solution structure of HbCO A was refined using stereospecifically assigned methyl groups and residual dipolar couplings based on our previous NMR structure. The tertiary structures of individual chains were found to be very similar to the X-ray structures, while the quaternary structures in solution with low-salt resembled the X-ray R structure more than the R2 structure. On the basis of chemical shift perturbation by inositol hexaphosphate (IHP) titration and docking, we identified five possible IHP binding sites in HbCO A. Amide-water proton exchange experiments demonstrated that ?Thr38 located in the ?1?2 interface and several loop regions in both ?- and ?-chains were dynamic on the sub-second timescale. Side-chain methyl dynamics revealed that methyl groups in the ?1?2 interface were dynamic, but those in the ?1?1 interface were quite rigid on the ns-ps and ms-µs timescales. All the data strongly suggest a dynamic ?1?2 interface that allows conformational changes among different forms (like T, R, and R2) easily in solution. Binding of IHP to HbCO A induced small structural and dynamics changes in the ?1?2 interface and the regions around the hemes, but did not increase the conformational entropy of HbCO A. The binding also caused conformational changes on the ms timescale, very likely arising from the relative motion of the ?1?1 dimer with respect to the ?2?2 dimer. Heterotropic effectors like IHP may change the oxygen affinity of Hb through modulating the relative motion of the two dimers and then further altering the structure of heme binding regions. PMID:23901897

Fan, Jing-Song; Zheng, Yu; Choy, Wing-Yiu; Simplaceanu, Virgil; Ho, Nancy T.; Ho, Chien; Yang, Daiwen

2014-01-01

354

AR-NE3A, a New Macromolecular Crystallography Beamline for Pharmaceutical Applications at the Photon Factory  

NASA Astrophysics Data System (ADS)

Recent advances in high-throughput techniques for macromolecular crystallography have highlighted the importance of structure-based drug design (SBDD), and the demand for synchrotron use by pharmaceutical researchers has increased. Thus, in collaboration with Astellas Pharma Inc., we have constructed a new high-throughput macromolecular crystallography beamline, AR-NE3A, which is dedicated to SBDD. At AR-NE3A, a photon flux up to three times higher than those at existing high-throughput beams at the Photon Factory, AR-NW12A and BL-5A, can be realized at the same sample positions. Installed in the experimental hutch are a high-precision diffractometer, fast-readout, high-gain CCD detector, and sample exchange robot capable of handling more than two hundred cryo-cooled samples stored in a Dewar. To facilitate high-throughput data collection required for pharmaceutical research, fully automated data collection and processing systems have been developed. Thus, sample exchange, centering, data collection, and data processing are automatically carried out based on the user's pre-defined schedule. Although Astellas Pharma Inc. has a priority access to AR-NE3A, the remaining beam time is allocated to general academic and other industrial users.

Yamada, Yusuke; Hiraki, Masahiko; Sasajima, Kumiko; Matsugaki, Naohiro; Igarashi, Noriyuki; Amano, Yasushi; Warizaya, Masaichi; Sakashita, Hitoshi; Kikuchi, Takashi; Mori, Takeharu; Toyoshima, Akio; Kishimoto, Shunji; Wakatsuki, Soichi

2010-06-01

355

AR-NE3A, a New Macromolecular Crystallography Beamline for Pharmaceutical Applications at the Photon Factory  

SciTech Connect

Recent advances in high-throughput techniques for macromolecular crystallography have highlighted the importance of structure-based drug design (SBDD), and the demand for synchrotron use by pharmaceutical researchers has increased. Thus, in collaboration with Astellas Pharma Inc., we have constructed a new high-throughput macromolecular crystallography beamline, AR-NE3A, which is dedicated to SBDD. At AR-NE3A, a photon flux up to three times higher than those at existing high-throughput beams at the Photon Factory, AR-NW12A and BL-5A, can be realized at the same sample positions. Installed in the experimental hutch are a high-precision diffractometer, fast-readout, high-gain CCD detector, and sample exchange robot capable of handling more than two hundred cryo-cooled samples stored in a Dewar. To facilitate high-throughput data collection required for pharmaceutical research, fully automated data collection and processing systems have been developed. Thus, sample exchange, centering, data collection, and data processing are automatically carried out based on the user's pre-defined schedule. Although Astellas Pharma Inc. has a priority access to AR-NE3A, the remaining beam time is allocated to general academic and other industrial users.

Yamada, Yusuke; Hiraki, Masahiko; Sasajima, Kumiko; Matsugaki, Naohiro; Igarashi, Noriyuki; Kikuchi, Takashi; Mori, Takeharu; Toyoshima, Akio; Kishimoto, Shunji; Wakatsuki, Soichi [Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization, 1-1 Oho, Tsukuba, Ibaraki, 305-0801 (Japan); Amano, Yasushi; Warizaya, Masaichi; Sakashita, Hitoshi [Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tukuba, Ibaraki, 300-8585 (Japan)

2010-06-23

356

A Versatile Microparticle-Based Immunoaggregation Assay for Macromolecular Biomarker Detection and Quantification  

PubMed Central

The rapid, sensitive and low-cost detection of macromolecular biomarkers is critical in clinical diagnostics, environmental monitoring, research, etc. Conventional assay methods usually require bulky, expensive and designated instruments and relative long assay time. For hospitals and laboratories that lack immediate access to analytical instruments, fast and low-cost assay methods for the detection of macromolecular biomarkers are urgently needed. In this work, we developed a versatile microparticle (MP)-based immunoaggregation method for the detection and quantification of macromolecular biomarkers. Antibodies (Abs) were firstly conjugated to MP through streptavidin-biotin interaction; the addition of macromolecular biomarkers caused the aggregation of Ab-MPs, which were subsequently detected by an optical microscope or optical particle sizer. The invisible nanometer-scale macromolecular biomarkers caused detectable change of micrometer-scale particle size distributions. Goat anti-rabbit immunoglobulin and human ferritin were used as model biomarkers to demonstrate MP-based immunoaggregation assay in PBS and 10% FBS to mimic real biomarker assay in the complex medium. It was found that both the number ratio and the volume ratio of Ab-MP aggregates caused by biomarker to all particles were directly correlated to the biomarker concentration. In addition, we found that the detection range could be tuned by adjusting the Ab-MP concentration. We envision that this novel MP-based immunoaggregation assay can be combined with multiple detection methods to detect and quantify macromolecular biomarkers at the nanogram per milliliter level. PMID:25658837

Wu, Haiyan; Han, Yu; Yang, Xi; Chase, George G.; Tang, Qiong; Lee, Chen-Jung; Cao, Bin; Zhe, Jiang; Cheng, Gang

2015-01-01

357

Automating crystallographic structure solution and refinement of protein–ligand complexes  

PubMed Central

High-throughput drug-discovery and mechanistic studies often require the determination of multiple related crystal structures that only differ in the bound ligands, point mutations in the protein sequence and minor conformational changes. If performed manually, solution and refinement requires extensive repetition of the same tasks for each structure. To accelerate this process and minimize manual effort, a pipeline encompassing all stages of ligand building and refinement, starting from integrated and scaled diffraction intensities, has been implemented in Phenix. The resulting system is able to successfully solve and refine large collections of structures in parallel without extensive user intervention prior to the final stages of model completion and validation. PMID:24419387

Echols, Nathaniel; Moriarty, Nigel W.; Klei, Herbert E.; Afonine, Pavel V.; Bunkóczi, Gábor; Headd, Jeffrey J.; McCoy, Airlie J.; Oeffner, Robert D.; Read, Randy J.; Terwilliger, Thomas C.; Adams, Paul D.

2014-01-01

358

Structural and Electronic Properties of a Wide-Gap Quaternary Solid Solution: \\(Zn, Mg\\) \\(S, Se\\)  

NASA Astrophysics Data System (ADS)

The structural properties of the (Zn, Mg) (S, Se) solid solutions are determined by a combination of the computational alchemy and the cluster expansion methods with Monte Carlo simulations. We determine the phase diagram of the alloy and show that the homogeneous phase is characterized by a large amount of short-range order occurring among first-nearest neighbors. Electronic-structure calculations performed using the special quasirandom structure approach indicate that the energy gap of the alloy is rather sensitive to this short-range order.

Saitta, A. M.; de Gironcoli, S.; Baroni, S.

1998-06-01

359

Solution of quadratic matrix equations for free vibration analysis of structures.  

NASA Technical Reports Server (NTRS)

An efficient digital computer procedure and the related numerical algorithm are presented herein for the solution of quadratic matrix equations associated with free vibration analysis of structures. Such a procedure enables accurate and economical analysis of natural frequencies and associated modes of discretized structures. The numerically stable algorithm is based on the Sturm sequence method, which fully exploits the banded form of associated stiffness and mass matrices. The related computer program written in FORTRAN V for the JPL UNIVAC 1108 computer proves to be substantially more accurate and economical than other existing procedures of such analysis. Numerical examples are presented for two structures - a cantilever beam and a semicircular arch.

Gupta, K. K.

1973-01-01

360

Solution structure of CEH-37 homeodomain of the nematode Caenorhabditis elegans  

SciTech Connect

Highlights: •We have determined solution structures of CEH-37 homedomain. •CEH-37 HD has a compact ?-helical structure with HTH DNA binding motif. •Solution structure of CEH-37 HD shares its molecular topology with that of the homeodomain proteins. •Residues in the N-terminal region and HTH motif are important in binding to Caenorhabditis elegans telomeric DNA. •CEH-37 could play an important role in telomere function via DNA binding. -- Abstract: The nematode Caenorhabditis elegans protein CEH-37 belongs to the paired OTD/OTX family of homeobox-containing homeodomain proteins. CEH-37 shares sequence similarity with homeodomain proteins, although it specifically binds to double-stranded C. elegans telomeric DNA, which is unusual to homeodomain proteins. Here, we report the solution structure of CEH-37 homeodomain and molecular interaction with double-stranded C. elegans telomeric DNA using nuclear magnetic resonance (NMR) spectroscopy. NMR structure shows that CEH-37 homeodomain is composed of a flexible N-terminal region and three ?-helices with a helix-turn-helix (HTH) DNA binding motif. Data from size-exclusion chromatography and fluorescence spectroscopy reveal that CEH-37 homeodomain interacts strongly with double-stranded C. elegans telomeric DNA. NMR titration experiments identified residues responsible for specific binding to nematode double-stranded telomeric DNA. These results suggest that C. elegans homeodomain protein, CEH-37 could play an important role in telomere function via DNA binding.

Moon, Sunjin [Structural Biochemistry and Molecular Biophysics Lab, Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)] [Structural Biochemistry and Molecular Biophysics Lab, Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Yong Woo; Kim, Woo Taek [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)] [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Weontae, E-mail: wlee@spin.yonsei.ac.kr [Structural Biochemistry and Molecular Biophysics Lab, Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)] [Structural Biochemistry and Molecular Biophysics Lab, Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

2014-01-10

361

Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).  

PubMed

More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40% of the cellular volume on average is occupied by all sorts of molecules. Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc). Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one. In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1). [Formula: see text] Figure 1. Left: number of articles containing the word 'crowding' as a keyword limited to the biological and chemical science domains (source: ISI Web of Science). The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012). Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus). To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international conference held in Ascona from 10 to 14 June 2012. In the unique scenario of the Maggiore lake and absorbed in the magic atmosphere of the Centro Stefano Franscini (CSF) at Monte Verità, we enjoyed three-and-a-half days of intense and inspiring activity, where not only many of the most prominent scientists working on macromolecular crowding, but also experts in closely related fields such as colloids and soft matter presented their work. The meeting was intended and has been organized to bring theoreticians and experimentalists together in the attempt to promote an active dialogue. Moreover, we wanted different disciplines to be represented, notably physics and chemistry, besides biology, as cross-fertilization is proving an increasingly fundamental source of inspiration and advancement. This issue of Physical Biology (PB) features a selection of the oral contributions presented at the conference, expanded in the form of research or review articles. PB, one of the scientific journals of the Institute of Physics (IOP), is one of the most dynamic and lively forums active at the interface between biology on one side, and physics and mathematics on the other. As its mission is stated by IOP, PB 'focuses on research in which physics-based approaches lead to new insights into biological systems at all scales of space and time, and all levels of complexity'. For these reasons, and also in view of its high reputation and broad readership, PB appears to be the ideal place for disseminating the thriving pieces of research presented at the conference. We are extremely grateful to PB and its kind and efficient editorial staff who helped make this issue a great scientific follow-up to the conference. The opening lecture of the conference, the first of four day-opening keynote lectures, was given by Allen P Minton from NIH (USA), possibly the most influential among the pioneers in the field. He provided a lucid and well-thought-out overview of the concept of macromolecular crowding through an exhaustive chronological account of the major milestones. It is clear that the con

Foffi, G; Pastore, A; Piazza, F; Temussi, P A

2013-08-01

362

Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012)  

NASA Astrophysics Data System (ADS)

More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40% of the cellular volume on average is occupied by all sorts of molecules. Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc). Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one. In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1). Figure 1. Figure 1. Left: number of articles containing the word 'crowding' as a keyword limited to the biological and chemical science domains (source: ISI Web of Science). The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012). Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus). To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international conference held in Ascona from 10 to 14 June 2012. In the unique scenario of the Maggiore lake and absorbed in the magic atmosphere of the Centro Stefano Franscini (CSF) at Monte Verità, we enjoyed three-and-a-half days of intense and inspiring activity, where not only many of the most prominent scientists working on macromolecular crowding, but also experts in closely related fields such as colloids and soft matter presented their work. The meeting was intended and has been organized to bring theoreticians and experimentalists together in the attempt to promote an active dialogue. Moreover, we wanted different disciplines to be represented, notably physics and chemistry, besides biology, as cross-fertilization is proving an increasingly fundamental source of inspiration and advancement. This issue of Physical Biology (PB) features a selection of the oral contributions presented at the conference, expanded in the form of research or review articles. PB, one of the scientific journals of the Institute of Physics (IOP), is one of the most dynamic and lively forums active at the interface between biology on one side, and physics and mathematics on the other. As its mission is stated by IOP, PB 'focuses on research in which physics-based approaches lead to new insights into biological systems at all scales of space and time, and all levels of complexity'. For these reasons, and also in view of its high reputation and broad readership, PB appears to be the ideal place for disseminating the thriving pieces of research presented at the conference. We are extremely grateful to PB and its kind and efficient editorial staff who helped make this issue a great scientific follow-up to the conference. The opening lecture of the conference, the first of four day-opening keynote lectures, was given by Allen P Minton from NIH (USA), possibly the most influential among the pioneers in the field. He provided a lucid and well-thought-out overview of the concept of macromolecular crowding through an exhaustive chronological account of the major milestones. It is clear that the concept of excl

Foffi, G.; Pastore, A.; Piazza, F.; Temussi, P. A.

2013-08-01

363

Diffraction cartography: applying microbeams to macromolecular crystallography sample evaluation and data collection.  

PubMed

Crystals of biological macromolecules often exhibit considerable inter-crystal and intra-crystal variation in diffraction quality. This requires the evaluation of many samples prior to data collection, a practice that is already widespread in macromolecular crystallography. As structural biologists move towards tackling ever more ambitious projects, new automated methods of sample evaluation will become crucial to the success of many projects, as will the availability of synchrotron-based facilities optimized for high-throughput evaluation of the diffraction characteristics of samples. Here, two examples of the types of advanced sample evaluation that will be required are presented: searching within a sample-containing loop for microcrystals using an X-ray beam of 5 microm diameter and selecting the most ordered regions of relatively large crystals using X-ray beams of 5-50 microm in diameter. A graphical user interface developed to assist with these screening methods is also presented. For the case in which the diffraction quality of a relatively large crystal is probed using a microbeam, the usefulness and implications of mapping diffraction-quality heterogeneity (diffraction cartography) are discussed. The implementation of these techniques in the context of planned upgrades to the ESRF's structural biology beamlines is also presented. PMID:20693684

Bowler, Matthew W; Guijarro, Matias; Petitdemange, Sebastien; Baker, Isabel; Svensson, Olof; Burghammer, Manfred; Mueller-Dieckmann, Christoph; Gordon, Elspeth J; Flot, David; McSweeney, Sean M; Leonard, Gordon A

2010-08-01

364

The cytoplasmic cage domain of the mechanosensitive channel MscS is a sensor of macromolecular crowding.  

PubMed

Cells actively regulate the macromolecular excluded volume of the cytoplasm to maintain the reciprocal fraction of free aqueous solution that is optimal for intracellular processes. However, the mechanisms whereby cells sense this critical parameter remain unclear. The mechanosensitive channel of small conductance (MscS channel), which is the major regulator of turgor in bacteria, mediates efflux of small osmolytes in response to increased membrane tension. At moderate sustained tensions produced by a decrease in external osmolarity, MscS undergoes slow adaptive inactivation; however, it inactivates abruptly in the presence of cytoplasmic crowding agents. To understand the mechanism underlying this rapid inactivation, we combined extrapolated and equilibrium molecular dynamics simulations with electrophysiological analyses of MscS mutants to explore possible transitions of MscS and generated models of the resting and inactivated states. Our models suggest that the coupling of the gate formed by TM3 helices to the peripheral TM1-TM2 pairs depends on the axial position of the core TM3 barrel relative to the TM1-TM2 shaft and the state of the associated hollow cytoplasmic domain ("cage"). They also indicate that the tension-driven inactivation transition separates the gate from the peripheral helices and promotes kinks in TM3s at G113 and that this conformation is stabilized by association of the TM3b segment with the ? domain of the cage. We found that mutations destabilizing the TM3b-? interactions preclude inactivation and make the channel insensitive to crowding agents and voltage; mutations that strengthen this association result in a stable closed state and silent inactivation. Steered simulations showed that pressure exerted on the cage bottom in the inactivated state reduces the volume of the cage in the cytoplasm and at the same time increases the footprint of the transmembrane domain in the membrane, implying coupled sensitivity to both membrane tension and crowding pressure. The cage, therefore, provides feedback on the increasing crowding that disengages the gate and prevents excessive draining and condensation of the cytoplasm. We discuss the structural mechanics of cells surrounded by an elastic cell wall where this MscS-specific feedback mechanism may be necessary. PMID:24778428

Rowe, Ian; Anishkin, Andriy; Kamaraju, Kishore; Yoshimura, Kenjiro; Sukharev, Sergei

2014-05-01

365

The cytoplasmic cage domain of the mechanosensitive channel MscS is a sensor of macromolecular crowding  

PubMed Central

Cells actively regulate the macromolecular excluded volume of the cytoplasm to maintain the reciprocal fraction of free aqueous solution that is optimal for intracellular processes. However, the mechanisms whereby cells sense this critical parameter remain unclear. The mechanosensitive channel of small conductance (MscS channel), which is the major regulator of turgor in bacteria, mediates efflux of small osmolytes in response to increased membrane tension. At moderate sustained tensions produced by a decrease in external osmolarity, MscS undergoes slow adaptive inactivation; however, it inactivates abruptly in the presence of cytoplasmic crowding agents. To understand the mechanism underlying this rapid inactivation, we combined extrapolated and equilibrium molecular dynamics simulations with electrophysiological analyses of MscS mutants to explore possible transitions of MscS and generated models of the resting and inactivated states. Our models suggest that the coupling of the gate formed by TM3 helices to the peripheral TM1–TM2 pairs depends on the axial position of the core TM3 barrel relative to the TM1–TM2 shaft and the state of the associated hollow cytoplasmic domain (“cage”). They also indicate that the tension-driven inactivation transition separates the gate from the peripheral helices and promotes kinks in TM3s at G113 and that this conformation is stabilized by association of the TM3b segment with the ? domain of the cage. We found that mutations destabilizing the TM3b–? interactions preclude inactivation and make the channel insensitive to crowding agents and voltage; mutations that strengthen this association result in a stable closed state and silent inactivation. Steered simulations showed that pressure exerted on the cage bottom in the inactivated state reduces the volume of the cage in the cytoplasm and at the same time increases the footprint of the transmembrane domain in the membrane, implying coupled sensitivity to both membrane tension and crowding pressure. The cage, therefore, provides feedback on the increasing crowding that disengages the gate and prevents excessive draining and condensation of the cytoplasm. We discuss the structural mechanics of cells surrounded by an elastic cell wall where this MscS-specific feedback mechanism may be necessary. PMID:24778428

Rowe, Ian; Anishkin, Andriy; Kamaraju, Kishore; Yoshimura, Kenjiro

2014-01-01

366

Solution structure of sialyl Lewis X mimics studied by two-dimensional NMR  

NASA Astrophysics Data System (ADS)

A structure of the peptidic mimic of sialyl Lewis X (Sle X) (?- N-acetyl-neuraminyl-(2,3)-?- D-galactopyranosyl-(1,4)-[?- L-fucopyranosyl-(1,3)-?- D- N-acetyl-glucosamine]) in an aqueous solution was studied using two-dimensional 1H NMR spectroscopy. Complete assignments of 1H NMR chemical shift of the SLe X mimic have been performed. The presence of three conformers of the SLe X mimic in a solution was proposed by using distance geometry calculation based on NOE constraints, which were obtained from NOESY experiments. In addition, intermolecular interaction between the mimic and the crystal structure of E-selectin was refined using molecular dynamics. This suggested the conformational rearrangement of the functional groups of the conformers to the active sites of E-selectin. The relationship between the binding activities toward E-selectin and the three-dimensional structures of other mimics was also discussed.

Demura, Makoto; Noda, Masatoshi; Kajimoto, Tetsuya; Uchiyama, Taketo; Umemoto, Kimiko; Wong, Chi-Huey; Asakura, Tetsuo

2002-01-01

367

Dynamic structure factor of a stiff polymer in a glassy solution  

E-print Network

We provide a comprehensive overview of the current theoretical understanding of the dynamic structure factor of stiff polymers in semidilute solution based on the wormlike chain (WLC) model. We extend previous work by computing exact numerical coefficients and an expression for the dynamic mean square displacement (MSD) of a free polymer and compare various common approximations for the hydrodynamic interactions, which need to be treated accurately if one wants to extract quantitative estimates for model parameters from experimental data. A recent controversy about the initial slope of the dynamic structure factor is thereby resolved. To account for the interactions of the polymer with a surrounding (sticky) polymer solution, we analyze an extension of the WLC model, the glassy wormlike chain (GWLC), which predicts near power-law and logarithmic long-time tails in the dynamic structure factor.

J. Glaser; O. Hallatschek; K. Kroy

2008-05-29

368

A hybrid computational-experimental approach for automated crystal structure solution  

NASA Astrophysics Data System (ADS)

Crystal structure solution from diffraction experiments is one of the most fundamental tasks in materials science, chemistry, physics and geology. Unfortunately, numerous factors render this process labour intensive and error prone. Experimental conditions, such as high pressure or structural metastability, often complicate characterization. Furthermore, many materials of great modern interest, such as batteries and hydrogen storage media, contain light elements such as Li and H that only weakly scatter X-rays. Finally, structural refinements generally require significant human input and intuition, as they rely on good initial guesses for the target structure. To address these many challenges, we demonstrate a new hybrid approach, first-principles-assisted structure solution (FPASS), which combines experimental diffraction data, statistical symmetry information and first-principles-based algorithmic optimization to automatically solve crystal structures. We demonstrate the broad utility of FPASS to clarify four important crystal structure debates: the hydrogen storage candidates MgNH and NH3BH3; Li2O2, relevant to Li-air batteries; and high-pressure silane, SiH4.

Meredig, Bryce; Wolverton, C.

2013-02-01

369

Grain boundary structure and solute segregation in titanium-doped sapphire bicrystals  

SciTech Connect

Solute segregation to ceramic grain boundaries governs material processing and microstructure evolution, and can strongly influence material properties critical to engineering performance. Understanding the evolution and implications of grain boundary chemistry is a vital component in the greater effort to engineer ceramics with controlled microstructures. This study examines solute segregation to engineered grain boundaries in titanium-doped sapphire (Al2O3) bicrystals, and explores relationships between grain boundary structure and chemistry at the nanometer scale using spectroscopic and imaging techniques in the transmission electron microscope (TEM). Results demonstrate dramatic changes in solute segregation stemming from small fluctuations in grain boundary plane and structure. Titanium and silicon solute species exhibit strong tendencies to segregate to non-basal and basal grain boundary planes, respectively. Evidence suggests that grain boundary faceting occurs in low-angle twis t boundaries to accommodate nonequilibrium solute segregation related to slow specimen cooling rates, while faceting of tilt grain boundaries often occurs to expose special planes of the coincidence site lattice (CSL). Moreover, quantitative analysis of grain boundary chemistry indicates preferential segregation of charged defects to grain boundary dislocations. These results offer direct proof that static dislocations in ionic materials can assume a net charge, and emphasize the importance of interactions between charged point, line, and planar defects in ionic materials. Efforts to understand grain boundary chemistry in terms of space charge theory, elastic misfit and nonequilibrium segregation are discussed for the Al2O3 system.

Taylor, Seth T.

2002-05-17

370

Dispersions of nanocrystalline cellulose in aqueous polymer solutions: structure formation of colloidal rods.  

PubMed

The steady-state shear and linear viscoelastic deformations of semidilute suspensions of rod-shaped nanocrystalline cellulose (NCC) particles in 1.0% hydroxyethyl cellulose and carboxymethyl cellulose solutions were investigated. Addition of NCC at the onset of semidilute suspension concentration significantly altered the rheological and linear viscoelastic properties of semidilute polymer solutions. The low-shear viscosity values of polymers solutions were increased 20-490 times (depending on polymer molecular weight and functional groups) by the presence of NCC. NCC suspensions in polymer solutions exhibited yield stresses up to 7.12 Pa. Viscoelasticity measurements also showed that NCC suspended polymer solutions had higher linear elastic moduli than the loss moduli. All of those results revealed the gel formation of NCC particles and presence of internal structures. The formation of a weak gel structure was due to the nonadsorbing macromolecules which caused the depletion-induced interaction among NCC particles. A simple interaction energy model was used to show successfully the flocculation of NCC particles in the presence of nonadsorbing polymers. The model is based on the incorporation of the depletion interaction term between two parallel plates into the DLVO theory for cubic prismatic rod shaped NCC particles. PMID:22448630

Boluk, Yaman; Zhao, Liyan; Incani, Vanessa

2012-04-10

371

Effect of different alkaline solutions on crystalline structure of cellulose at different temperatures.  

PubMed

Effect of alkaline solutions such as 10% NaOH, NaOH/urea and NaOH/ethylene glycol solutions on crystalline structure of different cellulosic fibers (cotton linter and filter paper) was investigated at room temperature and -4°C. The highest dissolution of cotton linter and filter paper was observed in NaOH/ethylene glycol at both temperatures. X-ray patterns of treated cotton linter with different alkaline solutions at low temperature showed only two diffractions at 2?=12.5° and 21.0°, which belonged to the crystalline structure of cellulose II. CP/MAS (13)C NMR spectra showed the doublet peaks at 89.2ppm and 88.3ppm representing C4 resonance for cellulose I at room temperature, Whereas, at low temperature the doublet peaks were observed at 89.2ppm and 87.8ppm representing C4 resonance for cellulose II. Degree of polymerization of cellulose plays an important role in cellulose dissolution in different alkaline solutions and temperatures, where, a low temperature gives high dissolutions percentage with change in crystalline structure from cellulose I to cellulose II forms. PMID:25439945

Keshk, Sherif M A S

2015-01-22

372

Theory of Polymer Chains in Poor Solvent: Single-Chain Structure, Solution Thermodynamics and Theta Point  

E-print Network

Using the language of the Flory chi parameter, we develop a theory that unifies the treatment of the single-chain structure and the solution thermodynamics of polymers in poor solvents. The structure of a globule and its melting thermodynamics is examined using the self-consistent filed theory. Our results show that the chain conformation involves three states prior to the globule-to-coil transition: the fully-collapsed globule, the swollen globule and the molten globule, which are distinguished by the core density and the interfacial thickness. By examining the chain-length dependence of the melting of the swollen globule, we find universal scaling behavior in the chain properties near the Theta point. The information of density profile and free energy of the globule is used in the dilute solution thermodynamics to study the phase equilibrium of polymer solution. Our results show different scaling behavior of the solubility of polymers in the dilute solution compared to the F-H theory, both in the chi dependence and the chain-length dependence. From the perspectives of single chain structure and solution thermodynamics, our results verifies the consistency of the Theta point defined by different criteria in the limit of infinite chain length: the disappearance of the second viral coefficient, the abrupt change in chain size and the critical point in the phase diagram of the polymer solution. Our results show the value of chi at the Theta point is 0.5 (for the case of equal monomer and solvent volume), which coincides with the value predicted from the F-H theory.

Rui Wang; Zhen-Gang Wang

2014-06-05

373

Structure of 2 molar NaOH in aqueous solution from neutron diffraction and empirical potential structure refinement  

SciTech Connect

Neutron diffraction with isotopic substitution has been used to investigate aqueous solutions of 2M NaOH in the liquid state. The data were modeled using empirical potential structure refinement which allows for the extraction of the ion-water and water-water correlations. The data show that the ion-water radial distribution functions are in accordance with those found by previous studies on NaOH solutions and follow a trend which is dependent on the concentration of the solute. In particular, the shape of the hydroxide hydration shell is found to be concentration independent, but the number of water molecules occupying this shell increases with dilution. Additionally, the water-water correlations show that there is still a measurable effect on water structure with the addition of ions at this concentration, as the second shell in the water oxygen radial distribution function is compressed relative to the first shell. The data are also used to discuss the recent claims that the published radial distribution functions of water are unreliable, showing that data taken at different neutron sources, with different diffraction geometry and systematic errors lead to the same structural information when analyzed via a realistic modeling regime.

McLain, Sylvia E.; Imberti, Silvia; Soper, Alan K.; Botti, Alberto; Bruni, Fabio; Ricci, Maria Antonietta [ISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot, OXON OX11 0QX (United Kingdom); ISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot, OXON OX11 0QX, United Kingdom and CNR-ISC, Sezione di Firenze, via Madonna del Piano 10, 50019 Sesto Fiorentino (Finland) (Italy); ISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot, OXON OX11 0QX (United Kingdom); Dipartimento di Fisica E. Amaldi, Universita degli Studi Roma Tre, Via della Vasca Navale 84, 00146 Rome (Italy)

2006-09-01

374

Flow of polymer solutions in planar 90 degree micro-bends  

NASA Astrophysics Data System (ADS)

The characterization of flows containing macromolecules is critical for the optimal design of microfluidic systems for biochemical analyses. The effects on transport in microscale flows are significant because the flow behavior may be influenced by molecular interactions, both viscous and elastic forces dominate inertial forces at this length scale, and the macromolecular length scale L approaches the device length scale D. Our previous studies explored flows of semi-dilute DNA solutions in planar 90 degree micro-bends (L/D ˜ 0.09), a canonical microfluidic structure; macromolecular flows in this geometry on a macro or microscale had been essentially unexplored. A recirculation region present in the interior corner of the bend is enhanced with increasing Re (7 x 10-7 < Re < 8 x 10-4) and Wi (1 < Wi < 190). Flows of poly(ethylene) oxide (PEO) solutions are explored across a similar parameter range to determine the influence of polymer extensibility and flexibility on the instability. Comparison of flows of DNA and PEO solutions offers insight into physical mechanism for the formation of elastic instabilities in micro-geometries.

Liepmann, Dorian; Gulati, Shelly; Dutcher, Cari; Muller, Susan

2007-11-01

375

Macromolecular scaffolds for immobilizing small molecule microarrays in label-free detection of protein-ligand interactions on solid support.  

PubMed

We explored two macromolecular scaffolds, bovine serum albumin (BSA) and polyvinyl alcohol (PVA), as chemically complementary platforms for immobilizing small molecule compounds on functionalized glass slides. We conjugated biotin molecules to BSA and amine-derivatized PVA and subsequently immobilized the conjugates on epoxy-functionalized glass slides through reaction of free amine residues on BSA and PVA with surface-bound epoxy groups. We studied binding reactions of such immobilized small molecule targets with solution-phase protein probes using an oblique-incidence reflectivity difference scanning optical microscope. The results showed that both BSA and amine-derivatized PVA were effective and efficient as carriers of small molecules with NHS residues and fluoric residues and for immobilization on epoxy-coated solid surfaces. A significant fraction of the conjugated small molecules retain their innate chemical activity. PMID:19563213

Sun, Y S; Landry, J P; Fei, Y Y; Zhu, X D; Luo, J T; Wang, X B; Lam, K S

2009-07-01

376

Protein Modelling: What Happened to the “Protein Structure Gap”?  

PubMed Central

Computational modeling and prediction of three-dimensional macromolecular structures and complexes from their sequence has been a long standing vision in structural biology as it holds the promise to bypass part of the laborious process of experimental structure solution. Over the last two decades, a paradigm shift has occurred: starting from a situation where the “structure knowledge gap” between the huge number of protein sequences and small number of known structures has hampered the widespread use of structure-based approaches in life science research, today some form of structural information – either experimental or computational – is available for the majority of amino acids encoded by common model organism genomes. Template based homology modeling techniques have matured to a point where they are now routinely used to complement experimental techniques. With the scientific focus of interest moving towards larger macromolecular complexes and dynamic networks of interactions, the integration of computational modeling methods with low-resolution experimental techniques allows studying large and complex molecular machines. Computational modeling and prediction techniques are still facing a number of challenges which hamper the more widespread use by the non-expert scientist. For example, it is often difficult to convey the underlying assumptions of a computational technique, as well as the expected accuracy and structural variability of a specific model. However, these aspects are crucial to understand the limitations of a model, and to decide which interpretations and conclusions can be supported. PMID:24010712

Schwede, Torsten

2013-01-01

377

Solution structures of chromium(VI) complexes with glutathione and model thiols.  

PubMed

Chromium(VI) complexes of the most abundant biological reductant, glutathione (gamma-Glu-Cys-Gly, I), are among the likely initial reactive intermediates formed during the cellular metabolism of carcinogenic and genotoxic Cr(VI). Detailed structural characterization of such complexes in solutions has been performed by a combination of X-ray absorption fine structure (XAFS) and X-ray absorption near-edge structure (XANES) spectroscopies, electrospray mass spectrometry (ESMS), UV-vis spectroscopy, and kinetic studies. The Cr(VI) complexes of two model thiols, N-acetyl-2-mercaptoethylamine (II) and 4-bromobenzenethiol (III), were used for comparison. The Cr(VI)-thiolato complexes were generated quantitatively in weakly acidic aqueous solutions (for I and II) or in DMF solutions (for II) or isolated as a pure solid (for III). Contrary to some claims in the literature, no evidence was found for the formation of relatively stable Cr(IV) intermediates during the reactions of Cr(VI) with I in acidic aqueous solutions. The Cr(VI) complexes of I-III exist as tetrahedral [CrO(3)(SR)](-) (IVa) species in the solid state, in solutions of aprotic solvents such as DMF, or in the gas phase (under ESMS conditions). In aqueous or alcohol solutions, reversible addition of a solvent molecule occurs, with the formation of five-coordinate species, [CrO(3)(SR)L](-) (IVb, probably of a trigonal bipyramidal structure, L = H(2)O or MeOH), with a Cr-L bond length of 1.97(1) A (determined by XAFS data modeling). Complex IVb (L = H(2)O) is also formed (in an equilibrium mixture with [CrO(4)](2)(-)) at the first stage of reduction of Cr(VI) by I in neutral aqueous solutions (as shown by global kinetic analysis of time-dependent UV-vis spectra). This is the first observation of a reversible ligand addition reaction in Cr(VI) complexes. The formation of IVb (rather than IVa, as thought before) during the reactions of Cr(VI) with I in aqueous solutions is likely to be important for the reactivity of Cr(VI) in cellular media, including DNA and protein damage and inhibition of protein tyrosine phosphatases. PMID:14704084

Levina, Aviva; Lay, Peter A

2004-01-12

378

Solution structure of peptide AG4 used to form silver nanoparticles  

SciTech Connect

The preparation of silver nanoparticles (AgNPs) is of great interest due to their various biological activities, such as observed in their antimicrobial and wound healing actions. Moreover, the formation of AgNPs using silver-binding peptide has certain advantages because they can be made in aqueous solution at ambient temperature. The solution structure of the silver-binding peptide AG4 was determined using nuclear magnetic resonance spectroscopy, and the site of the AG4 interaction with AgNPs was elucidated.

Lee, Eunjung [Division of Bioscience and Biotechnology, RCD, Konkuk University, Hwayang-Dong 1, Kwangjin-Ku, Seoul 143-701 (Korea, Republic of); Kim, Dae-Hee [Department of Environmental Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Woo, Yoonkyung [Division of Bioscience and Biotechnology, RCD, Konkuk University, Hwayang-Dong 1, Kwangjin-Ku, Seoul 143-701 (Korea, Republic of); Hur, Ho-Gil [Department of Environmental Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Lim, Yoongho [Division of Bioscience and Biotechnology, RCD, Konkuk University, Hwayang-Dong 1, Kwangjin-Ku, Seoul 143-701 (Korea, Republic of)], E-mail: yoongho@konkuk.ac.kr

2008-11-21

379

Anomalous solvent transport in macromolecular coal networks. Final technical report, September 1, 1983-August 31, 1986. [n-propylamine, n-butylamine, diethylamine, dipropylamine  

SciTech Connect

The purpose of this research was to use the dynamic swelling (transport) technique as a probe of the macromolecular structure of the organic phase of coals. Specifically, we were interested in comparing the transport mechanisms of penetrants into coal with those of penetrants into highly crosslinked synthetic macromolecular structures which allegedly simulate the coal network structure. The main goals of this work were: (1) to investigate the dynamic swelling behavior of pyridine extracted and unextracted coal particles in pyridine vapor; (2) to investigate the dynamic swelling behavior of unextracted coal particles in analogous aliphatic amines; (3) to investigate the penetrant transport into crosslinked polystyrene using methyl ethyl ketone; (4) to investigate the dynamic swelling behavior of recently proposed, crosslinked, structures based on naphthalene which allegedly simulate the coal structure; (5) to determine, for each macromolecular network with appropriate swelling agents, the molecular weight between crosslinks using equilibrium swelling experiments; (6) to analyze dynamic swelling studies with three different physical models; and (7) to compare the relaxation and diffusional parameters of coal obtained from the previous analyses, to those of the highly crosslinked polymers and to present these correlations between the transport phenomena and the crosslinked structure in general. During the course of this work we also investigated: (1) the effect of functionality of the crosslink on the calculated value of the molecular weight between crosslinks using our non-Gaussian equation; (2) the thermoplastic and viscoelastic behavior of coal network structures using thermal analysis; (3) the velocity of the penetrant as a function of time and crosslinking ratio (for poly(2-hydroxyethyl methacrylate) only); and (4) porosimetry measurements on the coal particles. 152 refs., 131 figs., 58 tabs.

Peppas, N.A.; Barr-Howell, B.; Howell, J.M.; Riger, P.L.

1986-01-01

380

Solution structure and dynamics of human ubiquitin conjugating enzyme Ube2g2  

PubMed Central

Ube2g2 is an E2 enzyme which functions as part of the endoplasmic reticulum-associated degradation (ERAD) pathway responsible for identification and degradation of misfolded proteins in the endoplasmic reticulum. In tandem with a cognate E3 ligase, Ube2g2 assembles K48-linked polyubiquitin chains and then transfers them to substrate, leading ultimately to proteasomal degradation of the polyubiquitin-tagged substrate. We report here the solution structure and backbone dynamics of Ube2g2 solved by nuclear magnetic resonance spectroscopy. Although the solution structure agrees well with crystallographic structures for the E2 core, catalytically important loops (encompassing residues 95-107 and 130-135) flanking the active site cysteine are poorly defined. 15N spin relaxation and residual dipolar coupling analysis directly demonstrates that these two loops are highly dynamic in solution. These results suggest that Ube2g2 requires one or more of its protein partners, such as cognate E3, acceptor ubiquitin substrate or thiolester-linked donor ubiquitin, in order to assume its catalytically relevant conformation. Within the NMR structural ensemble, interactions were observed between His94 and the highly mobile loop residues Asp98 and Asp99, supporting a possible role for His94 as a general base activated by the carboxylate side-chains of Asp98 or Asp99. PMID:20014027

Ju, Tingting; Bocik, William; Majumdar, Ananya; Tolman, Joel R.

2009-01-01

381

Ceruloplasmin: Macromolecular Assemblies with Iron-Containing Acute Phase Proteins  

PubMed Central

Copper-containing ferroxidase ceruloplasmin (Cp) forms binary and ternary complexes with cationic proteins lactoferrin (Lf) and myeloperoxidase (Mpo) during inflammation. We present an X-ray crystal structure of a 2Cp-Mpo complex at 4.7 Å resolution. This structure allows one to identify major protein–protein interaction areas and provides an explanation for a competitive inhibition of Mpo by Cp and for the activation of p-phenylenediamine oxidation by Mpo. Small angle X-ray scattering was employed to construct low-resolution models of the Cp-Lf complex and, for the first time, of the ternary 2Cp-2Lf-Mpo complex in solution. The SAXS-based model of Cp-Lf supports the predicted 1?1 stoichiometry of the complex and demonstrates that both lobes of Lf contact domains 1 and 6 of Cp. The 2Cp-2Lf-Mpo SAXS model reveals the absence of interaction between Mpo and Lf in the ternary complex, so Cp can serve as a mediator of protein interactions in complex architecture. Mpo protects antioxidant properties of Cp by isolating its sensitive loop from proteases. The latter is important for incorporation of Fe3+ into Lf, which activates ferroxidase activity of Cp and precludes oxidation of Cp substrates. Our models provide the structural basis for possible regulatory role of these complexes in preventing iron-induced oxidative damage. PMID:23843990

Samygina, Valeriya R.; Sokolov, Alexey V.; Bourenkov, Gleb; Petoukhov, Maxim V.; Pulina, Maria O.; Zakharova, Elena T.; Vasilyev, Vadim B.; Bartunik, Hans; Svergun, Dmitri I.

2013-01-01

382

Ceruloplasmin: macromolecular assemblies with iron-containing acute phase proteins.  

PubMed

Copper-containing ferroxidase ceruloplasmin (Cp) forms binary and ternary complexes with cationic proteins lactoferrin (Lf) and myeloperoxidase (Mpo) during inflammation. We present an X-ray crystal structure of a 2Cp-Mpo complex at 4.7 Å resolution. This structure allows one to identify major protein-protein interaction areas and provides an explanation for a competitive inhibition of Mpo by Cp and for the activation of p-phenylenediamine oxidation by Mpo. Small angle X-ray scattering was employed to construct low-resolution models of the Cp-Lf complex and, for the first time, of the ternary 2Cp-2Lf-Mpo complex in solution. The SAXS-based model of Cp-Lf supports the predicted 1:1 stoichiometry of the complex and demonstrates that both lobes of Lf contact domains 1 and 6 of Cp. The 2Cp-2Lf-Mpo SAXS model reveals the absence of interaction between Mpo and Lf in the ternary complex, so Cp can serve as a mediator of protein interactions in complex architecture. Mpo protects antioxidant properties of Cp by isolating its sensitive loop from proteases. The latter is important for incorporation of Fe(3+) into Lf, which activates ferroxidase activity of Cp and precludes oxidation of Cp substrates. Our models provide the structural basis for possible regulatory role of these complexes in preventing iron-induced oxidative damage. PMID:23843990

Samygina, Valeriya R; Sokolov, Alexey V; Bourenkov, Gleb; Petoukhov, Maxim V; Pulina, Maria O; Zakharova, Elena T; Vasilyev, Vadim B; Bartunik, Hans; Svergun, Dmitri I

2013-01-01

383

Quantitative influence of macromolecular crowding on gene regulation kinetics  

PubMed Central

We introduce macromolecular crowding quantitatively into the model for kinetics of gene regulation in Escherichia coli. We analyse and compute the specific-site searching time for 180 known transcription factors (TFs) regulating 1300 operons. The time is between 160 s (e.g. for SoxS Mw = 12.91 kDa) and 1550 s (e.g. for PepA6 of Mw = 329.28 kDa). Diffusion coefficients for one-dimensional sliding are between for large proteins up to for small monomers or dimers. Three-dimensional diffusion coefficients in the cytoplasm are 2 orders of magnitude larger than 1D sliding coefficients, nevertheless the sliding enhances the binding rates of TF to specific sites by 1–2 orders of magnitude. The latter effect is due to ubiquitous non-specific binding. We compare the model to experimental data for LacI repressor and find that non-specific binding of the protein to DNA is activation- and not diffusion-limited. We show that the target location rate by LacI repressor is optimized with respect to microscopic rate constant for association to non-specific sites on DNA. We analyse the effect of oligomerization of TFs and DNA looping effects on searching kinetics. We show that optimal searching strategy depends on TF abundance. PMID:24121687

Tabaka, Marcin; Kalwarczyk, Tomasz; Ho?yst, Robert

2014-01-01

384

Macromolecular metallurgy of binary mesocrystals via designed multiblock terpolymers.  

PubMed

Self-assembling block copolymers provide access to the fabrication of various ordered phases. In particular, the ordered spherical phases can be used to engineer soft mesocrystals with domain size at the 5-100 nm scales. Simple block copolymers, such as diblock copolymers, form a limited number of mesocrystals. However multiblock copolymers are capable to form more complex mesocrystals. We demonstrate that designed B1AB2CB3 multiblock terpolymers, in which the A- and C-blocks form spherical domains and the packing of these spheres can be controlled by changing the lengths of the middle and terminal B-blocks, self-assemble into various binary mesocrystals with space group symmetries of a large number of binary ionic crystals, including NaCl, CsCl, ZnS, ?-BN, AlB2, CaF2, TiO2, ReO3, Li3Bi, Nb3Sn(A15), and ?-Al2O3. This approach can be generalized to other terpolymers as well as to tetrapolymers to obtain ternary mesocrystals. Our study provides a new concept of macromolecular metallurgy for producing crystal phases in a mesoscale and thus makes multiblock copolymers a robust platform for the engineering of functional materials. PMID:24528160

Xie, Nan; Liu, Meijiao; Deng, Hanlin; Li, Weihua; Qiu, Feng; Shi, An-Chang

2014-02-26

385

Evaluating the stoichiometry of macromolecular complexes using multisignal sedimentation velocity  

PubMed Central

Gleaning information regarding the molecular physiology of macromolecular complexes requires knowledge of their component stoichiometries. In this work, a relatively new means of analyzing sedimentation velocity (SV) data from the analytical ultracentrifuge is examined in detail. The method depends on collecting concentration profile data simultaneously using multiple signals, like Rayleigh interferometry and UV spectrophotometry. If the cosedimenting components of a complex are spectrally distinguishable, continuous sedimentation-coefficient distributions specific for each component can be calculated to reveal the molar ratio of the complex’s components. When combined with the hydrodynamic information available from the SV data, a stoichiometry can be derived. Herein, the spectral properties of sedimenting species are systematically explored to arrive at a predictive test for whether a set of macromolecules can be spectrally resolved in a multisignal SV (MSSV) experiment. Also, a graphical means of experimental design and criteria to judge the success of the spectral discrimination in MSSV are introduced. A detailed example of the analysis of MSSV experiments is offered, and the possibility of deriving equilibrium association constants from MSSV analyses is explored. Finally, successful implementations of MSSV are reviewed. PMID:21256217

Padrick, Shae B.; Brautigam, Chad A.

2011-01-01

386

Specific Ion effects on macromolecular interactions in escherichia coli extracts.  

PubMed

Protein characterization in situ remains a major challenge for protein science. Here, the interactions of ?Tat-GB1 in Escherichia coli cell extracts were investigated by NMR spectroscopy and size exclusion chromatography (SEC). ?Tat-GB1 was found to participate in high molecular weight complexes that remain intact at physiologically-relevant ionic strength. This observation helps to explain why ?Tat-GB1 was not detected by in-cell NMR spectroscopy. Extracts pre-treated with RNase A had a different SEC elution profile indicating that ?Tat-GB1 predominantly interacted with RNA. The roles of biological and laboratory ions in mediating macromolecular interactions were studied. Interestingly, the interactions of ?Tat-GB1 could be disrupted by biologically-relevant multivalent ions. The most effective shielding of interactions occurred in Mg(2+) -containing buffers. Moreover, a combination of RNA digestion and Mg(2+) greatly enhanced the NMR detection of ?Tat-GB1 in cell extracts. This article is protected by copyright. All rights reserved. PMID:25492389

Kyne, Ciara; Ruhle, Brian; Gautier, Virginie W; Crowley, Peter B

2014-12-01

387

Nucleic acid and protein structures and interactions in viruses investigated by laser Raman spectroscopy  

NASA Astrophysics Data System (ADS)

Raman spectroscopy may be profitably exploited to determine details of protein and nucleic acid structures and their mutual interactions in viruses and gene regulatory complexes. Present applications use data obtained from model nucleic acid crystals, fibers and solutions to reveal preferred backbone and nucleoside conformations for different morphological states of DNA and RNA in plant (TMV, BDMV) and bacterial viruses (P22, Pfl, Xf, Pf3, fd, Ifl, IKe). Interpretation of the results is enhanced by deconvolution methods which, in favorable cases, permit quantitative conclusions regarding macromolecular structures. Both equilibrium and dynamic Raman applications are described.

Thomas, George J.

1986-03-01

388

Concentration dependence of the structure of aqueous solutions of lutetium nitrate according to X-ray diffraction  

NASA Astrophysics Data System (ADS)

Aqueous solutions of lutetium nitrate over a wide range of concentrations are studied by X-ray diffraction under standard temperature and pressure. The low-angle peaks in experimental scattering intensity curves are interpreted. It is shown that the structure of these solutions can be of two types. It is found that a saturated solution and solutions concentrated to a molar ratio of 1: 20 have a quasi-crystalline structure resulting from interionic interactions. It is determined that dilute solutions form a water-like structure characterized by a tetrahedral network of hydrogen bonds between the water molecules. It is found that low-angle peaks also appear in the intensity curves of dilute solutions; this proves that the so-called "long-range" order is preserved in these solutions. It is revealed that in all the studied systems, the contributions to the total scattering pattern that are responsible for the occurrence of pre-peaks are intercationic interactions.

Smirnov, P. R.; Grechin, O. V.; Trostin, V. N.

2014-02-01

389

Oligonuclear copper complexes of a bioinspired pyrazolate-bridging ligand: synthesis, structures, and equilibria in solution.  

PubMed

The synthesis of a new bioinspired dinucleating ligand scaffold based on a bridging pyrazolate with appended bis[2-(1-methylimidazolyl)methyl]aminomethyl chelate arms is reported. This ligand forms very stable copper complexes, and a series of different species is present in solution depending on the pH. Interconversions between these solution species are tracked and characterized spectroscopically, and X-ray crystallographic structures of three distinct complexes that correspond to the species present in solution from acidic to basic pH have been determined. Overall, this provides a comprehensive picture of the copper coordination chemistry of the new ligand system. Alterations in the protonation state are accompanied by changes in nuclearity and pyrazolate binding, which cause pronounced changes in color and magnetic properties. Antiferromagnetic coupling between the copper(II) ions is switched on or off depending on the pyrazole binding mode. PMID:17425304

Prokofieva, Angelina; Prikhod'ko, Alexander I; Enyedy, Eva Anna; Farkas, Etelka; Maringgele, Walter; Demeshko, Serhiy; Dechert, Sebastian; Meyer, Franc

2007-05-14

390

Acta Cryst. (1997). B53, 916-922 Multi-Solution Genetic Algorithm Approach to Surface Structure Determination Using  

E-print Network

916 Acta Cryst. (1997). B53, 916-922 Multi-Solution Genetic Algorithm Approach to Surface Structure-solution genetic algorithm search method utilizing direct methods to solve surface structures from surface of approaches such as simulated annealing (Sheldrick, 1990; Bhat, 1990) and more recently genetic algorithms

Marks, Laurence D.

391

Solution Structure of the 2A Protease from a Common Cold Agent, Human Rhinovirus C2, Strain W12  

E-print Network

Solution Structure of the 2A Protease from a Common Cold Agent, Human Rhinovirus C2, Strain W12 al. (2014) Solution Structure of the 2A Protease from a Common Cold Agent, Human Rhinovirus C2 of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any

392

A simple quantitative model of macromolecular crowding effects on protein folding: Application to the murine prion protein(121-231)  

NASA Astrophysics Data System (ADS)

A model of protein folding kinetics is applied to study the effects of macromolecular crowding on protein folding rate and stability. Macromolecular crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to macromolecular crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121-231). The differential effect of macromolecular crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.

Bergasa-Caceres, Fernando; Rabitz, Herschel A.

2013-06-01

393

The local structure of Pd(x)Ce(1-x)O(2-x-?) solid solutions.  

PubMed

PdxCe1-xO2-x-? solid solutions, which are highly efficient catalysts for the low-temperature oxidation of carbon monoxide, were examined using a set of structural (XRD-PDF, HRTEM, XRD) and spectral (XPS, Raman spectroscopy) methods in combination with quantum-chemical calculations. A comparison of the experimental results and pair distribution function (PDF) modeling data enabled reliable verification of the model of non-isomorphic substitution of Ce(4+) ions by Pd(2+) ions in PdxCe1-xO2-x-? solid solutions. Palladium ions were shown to be in a near square planar environment with C4v symmetry, which is typical for Pd(2+) ions. Such a near square planar environment was revealed by Raman spectroscopy due to the appearance of the band at ? = 187 cm(-1), which corresponds to the A1 vibrational mode of Pd(2+) ions in [PdO4] subunits. The binding energy of Pd3d5/2 (Eb(Pd3d5/2)) for the Pd(2+) ion in the CeO2 lattice is 1 eV higher than that of Eb(Pd3d5/2) for PdO oxide due to a decrease in the Pd-O distances and the formation of more ionic bonds because of the displacement of Pd(2+) ions with respect to the position of Ce(4+) ions in the fluorite structure. Five structural models of solid solutions are considered in this work. As demonstrated by the DFT calculations, the most realistic model is based on the displacement of palladium ions leading to a near square planar PdO4 environment, which includes water molecules stabilizing the region of anion vacancies in their dissociated state as two hydroxyl groups. The introduction of water molecules in the composition of the PdxCe1-xO2-x-? solution leads to a decrease in the formation energy and to additional stabilization of palladium in the CeO2 matrix. The formation of PdxCe1-xO2-x-? solid solutions is accompanied by the dispersing effect caused by distortions of the fluorite structure induced by Pd(2+) ions. The coprecipitation method, which allows Pd(2+) ions to be introduced at the stage of fluorite structure formation, was demonstrated to be the optimal method for the synthesis of a homogeneous PdxCe1-xO2-x-? solid solution. PMID:24894189

Gulyaev, R V; Kardash, T Yu; Malykhin, S E; Stonkus, O A; Ivanova, A S; Boronin, A I

2014-07-14

394

2188 Biochemistry 1989, 28, 2188-2 198 Determination of the Three-Dimensional Solution Structure of the  

E-print Network

defined. The average atomic rms difference between the 42 individual SA structures and the mean structure-2 A for the backbone atoms and 1.5-3 8,for all atoms. One approach to improve the precision of such structure2188 Biochemistry 1989, 28, 2188-2 198 Determination of the Three-Dimensional Solution Structure

Clore, G. Marius

395

Formation of intermolecular crosslinks by the actinocin derivatives with DNA in interaction under conditions of semidilute solution  

NASA Astrophysics Data System (ADS)

Interaction of native calf thymus DNA (ctDNA) with the actinocin derivatives containing protonated diethylamino groups, dimethylamino groups and unsubstituted amino groups and having different length of the alkyl chain have been studied by the method of viscometry. An anomalous hydrodynamic behavior of solutions of DNA with very low amount of ligands prepared under conditions of semidilute solution was revealed. We assumed that such an anomalous behavior of solutions of DNA complexes with actinocin derivatives associated with the formation of intermolecular crosslinks while the preparation of the complex was in terms of overlapping of macromolecular coils in solution. Comparative study of the hydrodynamic behavior of the DNA complexes with various actinocin structures lead us to the conclusion of the formation of crosslinks by the compounds containing protonated diethylamino groups.

Osinnikova, D. N.; Moroshkina, E. B.

2014-12-01

396

Solution spectroelectrochemical cell for in situ X-ray absorption fine structure  

SciTech Connect

A purpose-built spectroelectrochemical cell for in situ fluorescence XAFS (X-ray Absorption Fine Structure) measurements of bulk solution species during constant-potential electrolysis is described. The cell performance was demonstrated by the collection of europium L{sub 3}-edge XANES (X-ray Absorption Near Edge Structure) throughout the course of electrolysis of an aqueous solution of EuCl{sub 3}{center_dot}6H{sub 2}O in 1 M H{sub 2}SO{sub 4}. The europium L{sub 3}-edge resonances reported here for the Eu{sup III} and Eu{sup II} ions demonstrate that their 2p{sub 3/2} {yields} 5d electronic transition probabilities are not the same.

Antonio, M.R.; Soderholm, L. [Argonne National Lab., IL (United States). Chemistry Div.; Song, I. [Case Western Reserve Univ., Cleveland, OH (United States)

1995-06-12

397

Numerical solution of quadratic matrix equations for free vibration analysis of structures  

NASA Technical Reports Server (NTRS)

This paper is concerned with the efficient and accurate solution of the eigenvalue problem represented by quadratic matrix equations. Such matrix forms are obtained in connection with the free vibration analysis of structures, discretized by finite 'dynamic' elements, resulting in frequency-dependent stiffness and inertia matrices. The paper presents a new numerical solution procedure of the quadratic matrix equations, based on a combined Sturm sequence and inverse iteration technique enabling economical and accurate determination of a few required eigenvalues and associated vectors. An alternative procedure based on a simultaneous iteration procedure is also described when only the first few modes are the usual requirement. The employment of finite dynamic elements in conjunction with the presently developed eigenvalue routines results in a most significant economy in the dynamic analysis of structures.

Gupta, K. K.

1975-01-01

398

Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes.  

PubMed

The lymphocyte response to phytohemagglutinin (PHA) as measured by [13H]thymidine incorporation is equally inhibited by 10(-5) to 10(-4) M concentrations of delta8, and delta9-tetrahydrocannabinol (THC), their 11-hydroxymetabolites, cannabidiol, cannabinol, cannabichromene, cannabicyclol. A similar inhibiting effect is produced by olivetol, which has the structure of the C ring common to all of these cannabinoids and their metabolites that accumulate in tissues. THC inhibits intracellular and intramolecular incorporation of thymidine, uridine, and leucine. This inhibition can be observed within 15 min after addition of THC to the culture medium. The cytotoxicity of THC is a function of the concentration of serum in the culture medium. The higher the concentration of serum, the more the cells are protected against the toxicity of THC. The cytotoxicity of THC is reversible by washing, after the cells have been incubated for 24 hr with the drug. Lymphocytes incubated with THC or olivetol present a significantly larger number of hypodiploid cells and a significant increase in segregational errors of chromosomes. The inhibitory effect of THC on macromolecular synthesis might be mediated by an alteration of the plasma membrane by the drug. PMID:844617

Nahas, G G; Morishima, A; Desoize, B

1977-04-01

399

Assembly of the cochlear gap junction macromolecular complex requires connexin 26  

PubMed Central

Hereditary deafness affects approximately 1 in 2,000 children. Mutations in the gene encoding the cochlear gap junction protein connexin 26 (CX26) cause prelingual, nonsyndromic deafness and are responsible for as many as 50% of hereditary deafness cases in certain populations. Connexin-associated deafness is thought to be the result of defective development of auditory sensory epithelium due to connexion dysfunction. Surprisingly, CX26 deficiency is not compensated for by the closely related connexin CX30, which is abundantly expressed in the same cochlear cells. Here, using two mouse models of CX26-associated deafness, we demonstrate that disruption of the CX26-dependent gap junction plaque (GJP) is the earliest observable change during embryonic development of mice with connexin-associated deafness. Loss of CX26 resulted in a drastic reduction in the GJP area and protein level and was associated with excessive endocytosis with increased expression of caveolin 1 and caveolin 2. Furthermore, expression of deafness-associated CX26 and CX30 in cell culture resulted in visible disruption of GJPs and loss of function. Our results demonstrate that deafness-associated mutations in CX26 induce the macromolecular degradation of large gap junction complexes accompanied by an increase in caveolar structures. PMID:24590285

Kamiya, Kazusaku; Yum, Sabrina W.; Kurebayashi, Nagomi; Muraki, Miho; Ogawa, Kana; Karasawa, Keiko; Miwa, Asuka; Guo, Xueshui; Gotoh, Satoru; Sugitani, Yoshinobu; Yamanaka, Hitomi; Ito-Kawashima, Shioko; Iizuka, Takashi; Sakurai, Takashi; Noda, Tetsuo; Minowa, Osamu; Ikeda, Katsuhisa

2014-01-01

400

Global Rigid Body Modeling of Macromolecular Complexes against Small-Angle Scattering Data  

PubMed Central

New methods to automatically build models of macromolecular complexes from high-resolution structures or homology models of their subunits or domains against x-ray or neutron small-angle scattering data are presented. Depending on the complexity of the object, different approaches are employed for the global search of the optimum configuration of subunits fitting the experimental data. An exhaustive grid search is used for hetero- and homodimeric particles and for symmetric oligomers formed by identical subunits. For the assemblies or multidomain proteins containing more then one subunit/domain per asymmetric unit, heuristic algorithms based on simulated annealing are used. Fast computational algorithms based on spherical harmonics representation of scattering amplitudes are employed. The methods allow one to construct interconnected models without steric clashes, to account for the particle symmetry and to incorporate information from other methods, on distances between specific residues or nucleotides. For multidomain proteins, addition of missing linkers between the domains is possible. Simultaneous fitting of multiple scattering patterns from subcomplexes or deletion mutants is incorporated. The efficiency of the methods is illustrated by their application to complexes of different types in several simulated and practical examples. Limitations and possible ambiguity of rigid body modeling are discussed and simplified docking criteria are provided to rank multiple models. The methods described are implemented in publicly available computer programs running on major hardware platforms. PMID:15923225

Petoukhov, Maxim V.; Svergun, Dmitri I.

2005-01-01

401

Macromolecular organization and in vitro growth characteristics of scaffold-free neocartilage grafts.  

PubMed

Recent advances in tissue engineering offer considerable promise for the repair of focal lesions in articular cartilage. Here we describe (1) the macromolecular organization of tissue-engineered neocartilage grafts at light and electron microscopic levels, (2) their in vitro development, and (3) the effect of chondrocyte dedifferentiation, induced by monolayer expansion, on their resultant structure. We show that grafts produced from primary cultures of chondrocytes are hyaline in appearance with identifiable zonal strata as evidenced by cell morphology, matrix organization, and immunohistochemical composition. Like native articular cartilage, their surface zone contains type I collagen, surface zone proteoglycan, biglycan and decorin with type II collagen, aggrecan, chondroitin sulfate, chondroitin-4-sulfate, and keratan sulfate, becoming more prominent with depth. Assessment of cell viability by Live/Dead staining and cell-cycle analysis with BrDU suggest that the in vitro tissue has a high cellular turnover and develops through both appositional and interstitial growth mechanisms. Meanwhile, cell-tracker studies with CMFDA (5-chloromethyl-fluorescein diacetate) demonstrate that cell sorting in vitro is not involved in their zonal organization. Finally, passage expansion of chondrocytes in monolayer culture causes progressive reductions in graft thickness, loss of zonal architecture, and a more fibrocartilaginous tissue histology, consistent with a dedifferentiating chondrocyte phenotype. PMID:17478447

Hayes, Anthony J; Hall, Amanda; Brown, Liesbeth; Tubo, Ross; Caterson, Bruce

2007-08-01

402

The confluence of structure and dynamics in lanthanide(III) chelates: how dynamics help define structure in solution  

PubMed Central

Coordination exchange processes tend to dominate the solution state behaviour of lanthanide chelates and generally prohibit the study of small conformational changes. In this article we take advantage of coordinatively rigid Eu3+ chelates to examine the small conformational changes that occur in these chelates as water dissociatively exchanges in and out of the inner coordination sphere. The results show that the time-averaged conformation of the chelate alters as the water exchange rate increases. This conformational change reflects a change in the hydration state (q/rLnH6) of the chelate. The hydration state has recently come to be expressed as two separate parameters q and rLnH. However, these two parameters simultaneously describe the same structural considerations which in solution, are indistinguishable and intrinsically related to, and dependent upon, the dissociative water exchange rate. This realization leads to the broader understanding that a solution state structure can only be appreciated with reference to the dynamics of the system. PMID:24100299

Webber, Benjamin C.; Woods, Mark

2013-01-01

403

The confluence of structure and dynamics in lanthanide(III) chelates: how dynamics help define structure in solution.  

PubMed

Coordination exchange processes tend to dominate the solution state behaviour of lanthanide chelates and generally prohibit the study of small conformational changes. In this article we take advantage of coordinatively rigid Eu(3+) chelates to examine the small conformational changes that occur in these chelates as water dissociatively exchanges in and out of the inner coordination sphere. The results show that the time-averaged conformation of the chelate alters as the water exchange rate increases. This conformational change reflects a change in the hydration state (q/r(LnH)(6)) of the chelate. The hydration state has recently come to be expressed as two separate parameters q and r(LnH). However, these two parameters simultaneously describe the same structural considerations which in solution are indistinguishable and intrinsically related to, and dependent upon, the dissociative water exchange rate. This realization leads to the broader understanding that a solution state structure can only be appreciated with reference to the dynamics of the system. PMID:24100299

Webber, Benjamin C; Woods, Mark

2014-01-01

404

Modelling and fabrication of step height control of a multilevel Si(100) structure in KOH solution  

NASA Astrophysics Data System (ADS)

A new model of the step height control of a micromachined multilevel Si(100) terraced structure by KOH anisotropic etching with one photomask is proposed. The main factors affecting the step height of the terraces include the etching rate and etching time of the KOH solution, the angle of misalignment from the lang110rang direction of the silicon crystallography and the geometry of the photomask pattern, especially the relation between the width array [bn] and the interval array [an] of the masked areas. The different step heights of the multilevel structure can be obtained by the different dimensions of the mask pattern. If the multilevel structure has the same step height, the widths [bn] and intervals [an] of the masked areas must be an arithmetic progression. This will simplify the experimental design for application. The fabrication of three-level to eight-level Si(100) terraced structures has been demonstrated on this model and experiments.

Chung, Chen-Kuei

2004-03-01

405

Pressure-induced structural and hydration changes of proteins in aqueous solutions.  

PubMed

The effects of elevated hydrostatic pressure on four representative proteins, lysozyme, human serum albumin, ubiquitin and RNase A, were investigated by using Fourier transform infrared (FTIR) spectroscopy, by principal component analysis (PCA) and by moving-window two-dimensional (MW2D) correlation analysis. In addition, we revealed the pressure-induced changes of secondary structure elements using curve fitting. With pressure increase, the amide I band shifted to lower wavenumbers, with a transition at 200 MPa, which was indicative of hydration enhancement. Moreover, the pressure-induced behavior of pure water was studied, similar transition pressure was observed with protein in aqueous solution, suggesting that structure change of water around 200 MPa caused a hydration enhancement of protein. Under pressure higher than 200 MPa, the structural changes of the four proteins were obviously different except for the common features shifting to lower wavenumbers with pressure, basically due to the distinct structural differences among them. PMID:22076342

Zhang, Min; Wu, Yuqing

2011-01-01

406

Thorium nanochemistry: the solution structure of the Th(IV)?hydroxo pentamer  

SciTech Connect

Tetravalent thorium exhibits a strong tendency towards hydrolysis and subsequent polymerization. Polymeric species play a crucial role in understanding thorium solution chemistry, since their presence causes apparent solubility several orders of magnitude higher than predicted by thermodynamic data bases. Although electrospray mass spectrometry (ESI MS) identifies Th(IV) dimers and pentamers unequivocally as dominant species close to the solubility limit, the molecular structure of Th{sub 5}(OH){sub y} polymers was hitherto unknown. In the present study, X-ray absorption fine structure (XAFS) spectroscopy, high energy X-ray scattering (HEXS) measurements, and quantum chemical calculations are combined to solve the pentamer structure. The most favourable structure is represented by two Th(IV) dimers linked by a central Th(IV) cation through hydroxide bridges.

Walther, Clemens; Rothe, Jörg; Schimmelpfennig, Bernd; Fuss, Markus (Karlsruher)

2012-10-10

407

Effective protein-protein interaction from structure factor data of a lysozyme solution  

SciTech Connect

We report the determination of an effective protein-protein central potential for a lysozyme solution, obtained from the direct inversion of the total structure factor of the system, as extracted from small angle neutron scattering. The inversion scheme rests on a hypernetted-chain relationship between the effective potential and the structural functions, and is preliminarily tested for the case of a Lennard-Jones interaction. The characteristics of our potential are discussed in comparison with current models of effective interactions in complex fluids. The phase behavior predictions are also investigated.

Abramo, M. C.; Caccamo, C.; Costa, D.; Ruberto, R.; Wanderlingh, U. [Dipartimento di Fisica e di Scienze della Terra, Università degli Studi di Messina and CNISM (Consorzio Nazionale Interuniversitario di Struttura della Materia) Viale F. Stagno d'Alcontres 31, 98166 Messina (Italy)] [Dipartimento di Fisica e di Scienze della Terra, Università degli Studi di Messina and CNISM (Consorzio Nazionale Interuniversitario di Struttura della Materia) Viale F. Stagno d'Alcontres 31, 98166 Messina (Italy); Cavero, M. [School of Chemistry and Physics, University of Kwazulu-Natal, Private Bag X01, Scottsville 3209, Pietermaritzburg (South Africa)] [School of Chemistry and Physics, University of Kwazulu-Natal, Private Bag X01, Scottsville 3209, Pietermaritzburg (South Africa); Pellicane, G. [School of Chemistry and Physics, University of Kwazulu-Natal, Private Bag X01, Scottsville 3209, Pietermaritzburg (South Africa) [School of Chemistry and Physics, University of Kwazulu-Natal, Private Bag X01, Scottsville 3209, Pietermaritzburg (South Africa); National Institute for Theoretical Physics (NITheP), KZN node, Pietermaritzburg (South Africa)

2013-08-07

408

Solution structure and dynamics of C-terminal regulatory domain of Vibrio vulnificus extracellular metalloprotease  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer We have determined solution structures of vEP C-terminal regulatory domain. Black-Right-Pointing-Pointer vEP C-ter100 has a compact {beta}-barrel structure with eight anti-parallel {beta}-strands. Black-Right-Pointing-Pointer Solution structure of vEP C-ter100 shares its molecular topology with that of the collagen-binding domain of collagenase. Black-Right-Pointing-Pointer Residues in the {beta}3 region of vEP C-ter100 might be important in putative ligand/receptor binding. Black-Right-Pointing-Pointer vEP C-ter100 interacts strongly with iron ion. -- Abstract: An extracellular metalloprotease (vEP) secreted by Vibrio vulnificus ATCC29307 is a 45-kDa proteolytic enzyme that has prothrombin activation and fibrinolytic activities during bacterial infection. The action of vEP could result in clotting that could serve to protect the bacteria from the host defense machinery. Very recently, we showed that the C-terminal propeptide (C-ter100), which is unique to vEP, is involved in regulation of vEP activity. To understand the structural basis of this function of vEP C-ter100, we have determined the solution structure and backbone dynamics using multidimensional nuclear magnetic resonance spectroscopy. The solution structure shows that vEP C-ter100 is composed of eight anti-parallel {beta}-strands with a unique fold that has a compact {beta}-barrel formation which stabilized by hydrophobic and hydrogen bonding networks. Protein dynamics shows that the overall structure, including loops, is very rigid and stabilized. By structural database analysis, we found that vEP C-ter100 shares its topology with that of the collagen-binding domain of collagenase, despite low sequence homology between the two domains. Fluorescence assay reveals that vEP C-ter100 interacts strongly with iron (Fe{sup 3+}). These findings suggest that vEP protease might recruit substrate molecules, such as collagen, by binding at C-ter100 and that vEP participates in iron uptake from iron-withholding proteins of the host cell during infection.

Yun, Ji-Hye; Kim, Heeyoun [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)] [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Park, Jung Eun [Department of Biotechnology, College of Natural Sciences, Chosun University, Gwangju 501-759 (Korea, Republic of)] [Department of Biotechnology, College of Natural Sciences, Chosun University, Gwangju 501-759 (Korea, Republic of); Lee, Jung Sup, E-mail: jsplee@mail.chosun.ac.kr [Department of Biotechnology, College of Natural Sciences, Chosun University, Gwangju 501-759 (Korea, Republic of); Lee, Weontae, E-mail: wlee@spin.yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)] [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

2013-01-11

409

Viscoelasticity of aqueous telechelic poly(ethylene oxide) solutions: Relaxation and structure  

Microsoft Academic Search

We present a rheology study of associating polymers. The associating polymers are telechelic, composed of a water-soluble backbone (polyethylene oxide) terminated by hydrophobic moieties (C16H33) . In aqueous solutions, these polymers self-assemble to form micellar structures. Above a critical concentration, approximately 1 wt % of polymer, bridging between the micelles forms a transient network. Traditionally, the viscoelastic response of these

L. A. Hough; H. D. Ou-Yang

2006-01-01

410

Solution structure and dynamics of Ufm1, a ubiquitin-fold modifier 1  

Microsoft Academic Search

The ubiquitin-fold modifier 1 (Ufm1) is one of various ubiquitin-like modifiers and conjugates to target proteins in cells through Uba5 (E1) and Ufc1 (E2). The Ufm1-system is conserved in metazoa and plants, suggesting its potential roles in various multicellular organisms. Herein, we analyzed the solution structure and dynamics of human Ufm1 (hsUfm1) by nuclear magnetic resonance spectroscopy. Although the global

Hiroaki Sasakawa; Eri Sakata; Yoshiki Yamaguchi; Masaaki Komatsu; Kanako Tatsumi; Eiki Kominami; Keiji Tanaka; Koichi. Kato

2006-01-01

411

Finite-Element Solution of the Eddy-Current Problem in Magnetic Structures  

Microsoft Academic Search

Analysis of the eddy-currentproblem in magnetic structures by the method of Finite-elements is presented. The linear diffusion equation representing the appropriate energy functional is described. The field region is discretised by triangular Finite-elements and the solution to the field problem is obtained by minimizing the energy functional with respect to each of the vertex values of the vector potential. Expressions

M. V. K. Chari

1974-01-01

412

Coupled BEM–FEM solutions for direct time domain soil–structure interaction analysis  

Microsoft Academic Search

A coupled BEM–FEM methodology is presented for 3D wave propagation and soil–structure interaction analysis in the direct time domain. The employed boundary element method (BEM) uses a new generation of the Stokes fundamental solutions that utilize the B-Spline family of polynomials. A standard finite element methodology for dynamic analysis along with direct integration in time is coupled to the BEM

D. C. Rizos; Z. Wang

2002-01-01

413

Structure and dimerization of translation initiation factor aIF5B in solution  

SciTech Connect

Translation initiation factor 5B (IF5B) is required for initiation of protein synthesis. The solution structure of archaeal IF5B (aIF5B) was analysed by small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS) and was indicated to be in both monomeric and dimeric form. Sedimentation equilibrium (SE) analytical ultracentrifugation (AUC) of aIF5B indicated that aIF5B forms irreversible dimers in solution but only to a maximum of 5.0-6.8% dimer. Sedimentation velocity (SV) AUC at higher speed also indicated the presence of two species, and the sedimentation coefficients s{sub 20,w}{sup 0} were determined to be 3.64 and 5.51 {+-} 0.29 S for monomer and dimer, respectively. The atomic resolution (crystallographic) structure of aIF5B (Roll-Mecak et al. [6]) was used to model monomer and dimer, and theoretical sedimentation coefficients for these models were computed (3.89 and 5.63 S, respectively) in good agreement with the sedimentation coefficients obtained from SV analysis. Thus, the structure of aIF5B in solution must be very similar to the atomic resolution structure of aIF5B. SAXS data were acquired in the same buffer with the addition of 2% glycerol to inhibit dimerization, and the resultant monomeric aIF5B in solution did indeed adopt a structure very similar to the one reported earlier for the protein in crystalline form. The p(r) function indicated an elongated conformation supported by a radius of gyration of 37.5 {+-} 0.2 {angstrom} and a maximum dimension of {approx}130 {angstrom}. The effects of glycerol on the formation of dimers are discussed. This new model of aIF5B in solution shows that there are universal structural differences between aIF5B and the homologous protein IF2 from Escherichia coli.

Carø VohlanderRasmussen, Louise; Oliveira, Cristiano Luis Pinto; Byron, Olwyn; Jensen, Janni Mosgaard; Pedersen, Jan Skov; Sperling-Petersen, Hans Uffe; Mortensen, Kim Kusk (Aarhus); (Glasgow)

2012-02-07

414

Organic solid solution composed of two structurally similar porphyrins for organic solar cells.  

PubMed

A solid solution of a 75:25 mixture of tetrabenzoporphyrin (BP) and dichloroacenaphtho[q]tribenzo[b,g,l]porphyrin (CABP) forms when they are generated in a matrix of (dimethyl(o-anisyl)silylmethyl)(dimethylphenylsilylmethyl)[60]fullerene. This solid solution provides structural and optoelectronic properties entirely different from those of either pristine compounds or a mixture at other blending ratios. The use of this BP:CABP solid solution for organic solar cell (OSC) devices resulted in a power conversion efficiency (PCE) value higher by 16 and 300% than the PCE values obtained for the devices using the single donor BP and CABP, respectively, in a planar heterojunction architecture. This increase originates largely from the increase in short circuit current density, and hence by enhanced charge carrier separation at the donor/acceptor interface, which was probably caused by suitable energy level for the solid solution state, where electronic coupling between the two porphyrins occurred. The results suggest that physical and chemical modulation in solid solution is beneficial as an operationally simple method to enhance OSC performance. PMID:25626088

Zhen, Yonggang; Tanaka, Hideyuki; Harano, Koji; Okada, Satoshi; Matsuo, Yutaka; Nakamura, Eiichi

2015-02-18

415

A comparison of the structure of solute clusters formed during thermal ageing and irradiation.  

PubMed

Nanometre scale clusters form in Cu-containing reactor pressure vessel (RPV) steels during neutron irradiation. These clusters have a deleterious effect on mechanical properties, which can result in embrittlement and limit the reactor operating life. Thermal ageing of RPV steels can also induce the formation of solute clusters but it is not clear how similar these are to those formed during irradiation. In this work atom probe tomography, combined with detailed structural assessments of the structure of solute clusters, is used to address this issue. A series of thermal ageing heat treatments has been performed on several high- and low-Ni RPV welds to produce 1-4 nm diameter solute clusters. The same materials have also been neutron irradiated. The results show that CuMnNiSi enriched clusters formed during thermal ageing have, on average, higher Cu contents and lower Mn, Ni and Si contents than those found in irradiation-induced clusters. The effect of increasing bulk Ni is to encourage the formation of clusters with significantly higher Ni content, slightly higher Mn and Si contents and significantly lower Cu contents. At very high doses and dose rates MnNiSi enriched clusters can form even in high-Cu welds. Despite differences in the compositions of individual clusters formed during irradiation and during thermal ageing, clusters in both exhibit similar structure. In particular, well developed clusters in both materials have Cu-enriched cores whose peripheries are enriched in Ni, Mn and, in most cases, Si. PMID:21227587

Hyde, J M; Sha, G; Marquis, E A; Morley, A; Wilford, K B; Williams, T J

2011-05-01

416

Electronic structure of hemin in solution studied by resonant X-ray emission spectroscopy and electronic structure calculations.  

PubMed

Resonant inelastic X-ray scattering spectra at the iron L-edge from hemin in dimethyl sulfoxide liquid solution are reported. Our experiments, which are interpreted with the help of electronic structure calculations, support earlier assignments of hemin-solvent interactions, including the iron spin state and the role of the chloride ligand obtained from a total fluorescence yield study. The analysis of the explicit radiative relaxation channels of 2p core-level excited iron, explored in the present work, allows for a rather quantitative assignment of the orbitals involved in the excitation-deexcitation process of the core-excited hemin in solution. We specifically distinguish between contributions of partially and fully occupied valence orbitals to the broad X-ray emission band. In addition, our calculations reveal a detailed picture of the character of these orbitals. PMID:25068599

Atak, Kaan; Golnak, Ronny; Xiao, Jie; Suljoti, Edlira; Pflüger, Mika; Brandenburg, Tim; Winter, Bernd; Aziz, Emad F

2014-08-21

417

Ion aggregation in high salt solutions. II. Spectral graph analysis of water hydrogen-bonding network and ion aggregate structures  

NASA Astrophysics Data System (ADS)

Graph theory in mathematics and computer science is the study of graphs that are structures with pairwise connections between any objects. Here, the spectral graph theory and molecular dynamics simulation method are used to describe both morphological variation of ion aggregates in high salt solutions and ion effects on water hydrogen-bonding network structure. From the characteristic value analysis of the adjacency matrices that are graph theoretical representations of ion clusters, ion networks, and water H-bond structures, we obtained the ensemble average eigenvalue spectra revealing intricate connectivity and topology of ion aggregate structure that can be classified as either ion cluster or ion network. We further show that there is an isospectral relationship between the eigenvalue spectra of ion networks in high KSCN solutions and those of water H-bonding networks. This reveals the isomorphic relationship between water H-bond structure and ion-ion network structure in KSCN solution. On the other hand, the ion clusters formed in high NaCl solutions are shown to be graph-theoretically and morphologically different from the ion network structures in KSCN solutions. These observations support the bifurcation hypothesis on large ion aggregate growth mechanism via either ion cluster or ion network formation. We thus anticipate that the present spectral graph analyses of ion aggregate structures and their effects on water H-bonding network structures in high salt solutions can provide important information on the specific ion effects on water structures and possibly protein stability resulting from protein-water interactions.

Choi, Jun-Ho; Cho, Minhaeng

2014-10-01

418

Structure determination of molecules of biochemical interest  

NASA Astrophysics Data System (ADS)

In the past year we have established a new laboratory for the determination of macromolecular structure. Currently, facilities are in place for data collection, data processing, molecular modeling and X-ray refinement of structures of up to 100,000 molecular weight in their crystallographic asymmetric unit. In parallel with establishing a new laboratory, we have pursued structure investigations of hemoglobin from the sea lamprey, aspartate carbamoyltransferase from Escherichia coli and p-nitrobenzylidine aminoguanidine, a small molecule which is an acceptor of the adenosine diphosphate ribosyl group in an enzyme mediated reaction. In addition to the structural studies above we have made a theoretical study by techniques of energy minimization of possible modes of aggregation of lamprey hemoglobin and the relationship between aggregate formation and cooperativity expressed in solutions by lamprey hemoglobin.

Honzatko, R. B.

1985-10-01

419

Functional regulation of CFTR-containing macromolecular complexes: a small-molecule inhibitor approach  

PubMed Central

SYNOPSIS CFTR has been shown to form multiple-protein macromolecular complexes with its interacting partners at discrete subcellular microdomains to modulate trafficking, transport and signaling in cells. Targeting protein-protein interactions within these macromolecular complexes would affect the expression or function of the CFTR channel. We specifically targeted PDZ-based LPA2-NHERF2 interaction within the CFTR-NHERF2-LPA2-containing macromolecular complexes at airway epithelia and tested its regulatory role on CFTR channel function. We identified a cell-permeable small-molecule compound that preferentially inhibits LPA2-NHERF2 interaction. We show that this compound can disrupt LPA2-NHERF2 interaction in cells and thus compromises the integrity of macromolecular complexes. Functionally, it elevates cAMP levels in proximity to CFTR and upregulates its channel activity. Our results demonstrate that CFTR Cl? channel function can be finely tuned by modulating PDZ-based protein-protein interactions within the CFTR-containing macromolecular complexes. Our study might help to identify novel therapeutic targets to treat diseases associated with dysfunctional CFTR Cl? channel. PMID:21299497

ZHANG, Weiqiang; PENMATSA, Himabindu; REN, Aixia; PUNCHIHEWA, Chandanamali; LEMOFF, Andrew; YAN, Bing; FUJII, Naoaki; NAREN, Anjaparavanda P.

2011-01-01