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1

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.

Adams, Paul D.; Afonine, Pavel V.; Bunkoczi, Gabor; 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

2

Ordered macromolecular structures in ferrofluid mixtures  

SciTech Connect

We have observed ordering of dilute dispersions of spherical and cylindrical macromolecules in magnetized ferrofluids. The order results from structural correlations between macromolecular and ferrofluid particles rather than from macroscopic magnetostatic effects. We have aligned elongated macromolecules by this technique and have obtained anisotropic neutron-diffraction patterns, which reflect the internal structure of the macromolecules. The method provides a tool for orienting suspended macromolecular assemblies which are not amenable to conventional alignment techniques.

Hayter, J.B.; Pynn, R.; Charles, S.; Skjeltorp, A.T.; Trewhella, J.; Stubbs, G.; Timmins, P.

1989-04-03

3

Solution-Phase Processes of Macromolecular Crystallization  

NASA Technical Reports Server (NTRS)

We have proposed, for the tetragonal form of chicken egg lysozyme, that solution phase assembly processes are needed to form the growth units for crystal nucleation and growth. The starting point for the self-association process is the monomeric protein, and the final crystallographic symmetry is defined by the initial dimerization interactions of the monomers and subsequent n-mers formed, which in turn are a function of the crystallization conditions. It has been suggested that multimeric proteins generally incorporate the underlying multimers symmetry into the final crystallographic symmetry. We posed the question of what happens to a protein that is known to grow as an n-mer when it is placed in solution conditions where it is monomeric. The trypsin-treated, or cut, form of the protein canavalin (CCAN) has been shown to nucleate and grow crystals as a trimer from neutral to slightly acidic solutions. Under these conditions the solution is composed almost wholly of trimers. The insoluble protein can be readily dissolved by weakly basic solution, which results in a solution that is monomeric. There are three possible outcomes to an attempt at crystallization of the protein under monomeric (high pH) conditions: 1) we will obtain the same crystals as under trimer conditions, but at different protein concentrations governed by the self association equilibria; 2) we will obtain crystals having a different symmetry, based upon a monomeric growth unit; 3) we will not obtain crystals. Obtaining the first result would be indicative that the solution-phase self-association process is critical to the crystal nucleation and growth process. The second result would be less clear, as it may also reflect a pH-dependent shift in the trimer-trimer molecular interactions. The third result, particularly for experiments in the transition pH's between trimeric and monomeric CCAN, would indicate that the monomer does not crystallize, and that solution phase self association is not part of the crystal nucleation and growth path. Results are presented for crystallization experiments of CCAN over the pH 6.8 to 9.6 range.

Pusey, Marc L.; Minamitani, Elizabeth Forsythe

2004-01-01

4

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

NASA Astrophysics Data System (ADS)

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 architectures is controlled by processing methods that rely on 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.

Kelley, Elizabeth G.; Murphy, Ryan P.; Seppala, Jonathan E.; Smart, Thomas P.; Hann, Sarah D.; Sullivan, Millicent O.; Epps, Thomas H.

2014-04-01

5

Macromolecular Crystallography and Structural Biology Databases at NIST.  

National Technical Information Service (NTIS)

In the late 1970s, macromolecular crystallography at NIST began with collaboration between NIST and NIH to establish a single-crystal neutron diffractometer. This instrument was constructed and employed to solve a number of crystal structures: bovine ribo...

G. L. Gilliland

2001-01-01

6

Macromolecular structure and self-assembly.  

PubMed

The output from the molecular biology revolution has grown steadily and logarithmically from the first protein sequence, insulin (Ryle AP et al 1955 Biochem J 60:541-556), the first three-dimensional atomic structure of a macromolecule, myoglobin (Kendrew JC et al 1960 Nature 185:422-427), the first DNA gene sequence, phi X174 gene J (Sanger F et al 1977 Nature 265:687-695) and the first genome sequence for a free-living organism, Haemophilus influenzae (Fleischmann RD et al 1995 Science 269:496-512) to the current situation where the output rate is close to one new gene sequence every few minutes, several new three-dimensional structures a day and a new (bacterial) genome completed every few months. Those working in this field must readjust their horizons to this changing situation every year or two. In the area of three-dimensional structure of macromolecules and macromolecular assemblies, the methods of X-ray crystallography, nuclear magnetic resonance and electron microscopy have combined to produce powerful insights into how these molecular machines work. In this paper, I present three examples of molecular machines whose structure tells us a lot about how they work. These are the light-driven proton pump bacteriorhodopsin, the ATP synthetase molecule which contains a tiny motor and generator, and the flagellar rotary motor which provides the thrust to power physical movement of the bacterial cell. The structure itself in three-dimensional detail is thus often seen to provide the most important single insight into how things work, reducing biology to chemistry and physics. The reductionist approach in this field seems to be limited only by the accuracy by which it is possible to describe inter- and intra-molecular interactions in terms of hydrogen bonds, van der Waals interactions and electrostatic forces. At present, there is no fundamental limit in sight. PMID:9653714

Henderson, R

1998-01-01

7

The structural dynamics of macromolecular processes  

PubMed Central

Summary Dynamic processes involving macromolecular complexes are essential to cell function. These processes take place over a wide variety of length scales from nanometers to micrometers, and over time scales from nanoseconds to many minutes. As a result, information from a variety of different experimental and computational approaches is required. We review the relevant sources of information and introduce a framework for integrating the data to produce representations of dynamic processes.

Russel, Daniel; Lasker, Keren; Phillips, Jeremy; Schneidman-Duhovny, Dina; Velazquez-Muriel, Javier A.; Sali, Andrej

2009-01-01

8

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

9

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

PubMed

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 architectures is controlled by processing methods that rely on 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; Sullivan, Millicent O; Epps, Thomas H

2014-01-01

10

Refinement of macromolecular structures against neutron data with SHELXL2013  

PubMed Central

Some of the improvements in SHELX2013 make SHELXL convenient to use for refinement of macromolecular structures against neutron data without the support of X-ray data. The new NEUT instruction adjusts the behaviour of the SFAC instruction as well as the default bond lengths of the AFIX instructions. This work presents a protocol on how to use SHELXL for refinement of protein structures against neutron data. It includes restraints extending the Engh & Huber [Acta Cryst. (1991), A47, 392–400] restraints to H atoms and discusses several of the features of SHELXL that make the program particularly useful for the investigation of H atoms with neutron diffraction. SHELXL2013 is already adequate for the refinement of small molecules against neutron data, but there is still room for improvement, like the introduction of chain IDs for the refinement of macromolecular structures.

Gruene, Tim; Hahn, Hinrich W.; Luebben, Anna V.; Meilleur, Flora; Sheldrick, George M.

2014-01-01

11

Analysis of conformational variation in macromolecular structural models.  

PubMed

Experimental conditions or the presence of interacting components can lead to variations in the structural models of macromolecules. However, the role of these factors in conformational selection is often omitted by in silico methods to extract dynamic information from protein structural models. Structures of small peptides, considered building blocks for larger macromolecular structural models, can substantially differ in the context of a larger protein. This limitation is more evident in the case of modeling large multi-subunit macromolecular complexes using structures of the individual protein components. Here we report an analysis of variations in structural models of proteins with high sequence similarity. These models were analyzed for sequence features of the protein, the role of scaffolding segments including interacting proteins or affinity tags and the chemical components in the experimental conditions. Conformational features in these structural models could be rationalized by conformational selection events, perhaps induced by experimental conditions. This analysis was performed on a non-redundant dataset of protein structures from different SCOP classes. The sequence-conformation correlations that we note here suggest additional features that could be incorporated by in silico methods to extract dynamic information from protein structural models. PMID:22808083

Srivastava, Sandeep Kumar; Gayathri, Savitha; Manjasetty, Babu A; Gopal, Balasubramanian

2012-01-01

12

MMDB and VAST+: tracking structural similarities between macromolecular complexes.  

PubMed

The computational detection of similarities between protein 3D structures has become an indispensable tool for the detection of homologous relationships, the classification of protein families and functional inference. Consequently, numerous algorithms have been developed that facilitate structure comparison, including rapid searches against a steadily growing collection of protein structures. To this end, NCBI's Molecular Modeling Database (MMDB), which is based on the Protein Data Bank (PDB), maintains a comprehensive and up-to-date archive of protein structure similarities computed with the Vector Alignment Search Tool (VAST). These similarities have been recorded on the level of single proteins and protein domains, comprising in excess of 1.5 billion pairwise alignments. Here we present VAST+, an extension to the existing VAST service, which summarizes and presents structural similarity on the level of biological assemblies or macromolecular complexes. VAST+ simplifies structure neighboring results and shows, for macromolecular complexes tracked in MMDB, lists of similar complexes ranked by the extent of similarity. VAST+ replaces the previous VAST service as the default presentation of structure neighboring data in NCBI's Entrez query and retrieval system. MMDB and VAST+ can be accessed via http://www.ncbi.nlm.nih.gov/Structure. PMID:24319143

Madej, Thomas; Lanczycki, Christopher J; Zhang, Dachuan; Thiessen, Paul A; Geer, Renata C; Marchler-Bauer, Aron; Bryant, Stephen H

2014-01-01

13

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.

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

2011-01-01

14

E-MSD: the European Bioinformatics Institute Macromolecular Structure Database  

PubMed Central

The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd) is designed to be a single access point for protein and nucleic acid structures and related information. The database is derived from Protein Data Bank (PDB) entries. Relational database technologies are used in a comprehensive cleaning procedure to ensure data uniformity across the whole archive. The search database contains an extensive set of derived properties, goodness-of-fit indicators, and links to other EBI databases including InterPro, GO, and SWISS-PROT, together with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is available, coupled with a fast secondary structure domain search tool.

Boutselakis, H.; Dimitropoulos, D.; Fillon, J.; Golovin, A.; Henrick, K.; Hussain, A.; Ionides, J.; John, M.; Keller, P. A.; Krissinel, E.; McNeil, P.; Naim, A.; Newman, R.; Oldfield, T.; Pineda, J.; Rachedi, A.; Copeland, J.; Sitnov, A.; Sobhany, S.; Suarez-Uruena, A.; Swaminathan, J.; Tagari, M.; Tate, J.; Tromm, S.; Velankar, S.; Vranken, W.

2003-01-01

15

Automated identification of elemental ions in macromolecular crystal structures  

PubMed Central

Many macromolecular model-building and refinement programs can automatically place solvent atoms in electron density at moderate-to-high resolution. This process frequently builds water molecules in place of elemental ions, the identification of which must be performed manually. The solvent-picking algorithms in phenix.refine have been extended to build common ions based on an analysis of the chemical environment as well as physical properties such as occupancy, B factor and anomalous scattering. The method is most effective for heavier elements such as calcium and zinc, for which a majority of sites can be placed with few false positives in a diverse test set of structures. At atomic resolution, it is observed that it can also be possible to identify tightly bound sodium and magnesium ions. A number of challenges that contribute to the difficulty of completely automating the process of structure completion are discussed.

Echols, Nathaniel; Morshed, Nader; Afonine, Pavel V.; McCoy, Airlie J.; Miller, Mitchell D.; Read, Randy J.; Richardson, Jane S.; Terwilliger, Thomas C.; Adams, Paul D.

2014-01-01

16

Automated identification of elemental ions in macromolecular crystal structures.  

PubMed

Many macromolecular model-building and refinement programs can automatically place solvent atoms in electron density at moderate-to-high resolution. This process frequently builds water molecules in place of elemental ions, the identification of which must be performed manually. The solvent-picking algorithms in phenix.refine have been extended to build common ions based on an analysis of the chemical environment as well as physical properties such as occupancy, B factor and anomalous scattering. The method is most effective for heavier elements such as calcium and zinc, for which a majority of sites can be placed with few false positives in a diverse test set of structures. At atomic resolution, it is observed that it can also be possible to identify tightly bound sodium and magnesium ions. A number of challenges that contribute to the difficulty of completely automating the process of structure completion are discussed. PMID:24699654

Echols, Nathaniel; Morshed, Nader; Afonine, Pavel V; McCoy, Airlie J; Miller, Mitchell D; Read, Randy J; Richardson, Jane S; Terwilliger, Thomas C; Adams, Paul D

2014-04-01

17

Macromolecular crowding can account for RNase-sensitive constraint of bacterial nucleoid structure  

SciTech Connect

The shape and compaction of the bacterial nucleoid may affect the accessibility of genetic material to the transcriptional machinery in natural and synthetic systems. To investigate this phenomenon, the nature and contribution of RNA and protein to the compaction of nucleoids that had been gently released from Escherichia coli cells were investigated using fluorescent and transmission electron microscopy. We propose that the removal of RNA from the bacterial nucleoid affects nucleoid compaction by altering the branching density and molecular weight of the nucleoid. We show that a common detergent in nucleoid preparations, Brij 58, plays a previously unrecognized role as a macromolecular crowding agent. RNA-free nucleoids adopt a compact structure similar in size to exponential-phase nucleoids when the concentration of Brij 58 is increased, consistent with our hypothesis. We present evidence that control and protein-free nucleoids behave similarly in solutions containing a macromolecular crowding agent. These results show that the contribution to DNA compaction by nucleoid-associated proteins is small when compared to macromolecular crowding effects.

Foley, Patricia L. [School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853-5201 (United States)] [School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853-5201 (United States); Wilson, David B. [Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-5201 (United States)] [Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-5201 (United States); Shuler, Michael L., E-mail: mls50@cornell.edu [School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853-5201 (United States); Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853-5201 (United States)

2010-04-23

18

Macromolecular microcrystallography  

Microsoft Academic Search

Over a decade has passed since pioneering diffraction experiments on macromolecular microcrystals were performed at the European Synchrotron Radiation Facility. Since then the measurement of high-quality diffraction data for the purpose of structure determination has been transformed from a specialized experiment into routine practice at dedicated microfocus macromolecular crystallography beamlines at synchrotron facilities. In this article, we review the evolution

Gwyndaf Evans; Danny Axford; David Waterman; Robin L. Owen

2011-01-01

19

Timely deposition of macromolecular structures is necessary for peer review  

PubMed Central

Most of the macromolecular structures in the Protein Data Bank (PDB), which are used daily by thousands of educators and scientists alike, are determined by X-ray crystallography. It was examined whether the crystallographic models and data were deposited to the PDB at the same time as the publications that describe them were submitted for peer review. This condition is necessary to ensure pre-publication validation and the quality of the PDB public archive. It was found that a significant proportion of PDB entries were submitted to the PDB after peer review of the corresponding publication started, and many were only submitted after peer review had ended. It is argued that clear description of journal policies and effective policing is important for pre-publication validation, which is key in ensuring the quality of the PDB and of peer-reviewed literature.

Joosten, Robbie P.; Soueidan, Hayssam; Wessels, Lodewyk F. A.; Perrakis, Anastassis

2013-01-01

20

Timely deposition of macromolecular structures is necessary for peer review.  

PubMed

Most of the macromolecular structures in the Protein Data Bank (PDB), which are used daily by thousands of educators and scientists alike, are determined by X-ray crystallography. It was examined whether the crystallographic models and data were deposited to the PDB at the same time as the publications that describe them were submitted for peer review. This condition is necessary to ensure pre-publication validation and the quality of the PDB public archive. It was found that a significant proportion of PDB entries were submitted to the PDB after peer review of the corresponding publication started, and many were only submitted after peer review had ended. It is argued that clear description of journal policies and effective policing is important for pre-publication validation, which is key in ensuring the quality of the PDB and of peer-reviewed literature. PMID:24311569

Joosten, Robbie P; Soueidan, Hayssam; Wessels, Lodewyk F A; Perrakis, Anastassis

2013-12-01

21

Implications of macromolecular crowding for protein assembly  

Microsoft Academic Search

Recent studies have led to increased appreciation of the influence of excluded volume in solutions of high total macromolecular content (‘macromolecular crowding’) upon the various classes of reaction that lead to the assembly of proteins and protein complexes. In general, crowding is expected to stabilize native protein structure relative to less compact non-native structures and to favor the formation of

Allen P Minton

2000-01-01

22

Electrokinetic Behavior of Calcium Oxalate Monohydrate in Macromolecular Solutions.  

National Technical Information Service (NTIS)

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 b...

P. A. Curreri G. Y. Onoda B. Finlayson

1988-01-01

23

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

24

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

25

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

26

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

27

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).

Minor, Daniel L.

2010-01-01

28

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.

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

29

Dynamic simulation of concentrated macromolecular solutions with screened long-range hydrodynamic interactions: Algorithm and limitations  

NASA Astrophysics Data System (ADS)

Hydrodynamic interactions exert a critical effect on the dynamics of macromolecules. As the concentration of macromolecules increases, by analogy to the behavior of semidilute polymer solutions or the flow in porous media, one might expect hydrodynamic screening to occur. Hydrodynamic screening would have implications both for the understanding of macromolecular dynamics as well as practical implications for the simulation of concentrated macromolecular solutions, e.g., in cells. Stokesian dynamics (SD) is one of the most accurate methods for simulating the motions of N particles suspended in a viscous fluid at low Reynolds number, in that it considers both far-field and near-field hydrodynamic interactions. This algorithm traditionally involves an O(N3) operation to compute Brownian forces at each time step, although asymptotically faster but more complex SD methods are now available. Motivated by the idea of hydrodynamic screening, the far-field part of the hydrodynamic matrix in SD may be approximated by a diagonal matrix, which is equivalent to assuming that long range hydrodynamic interactions are completely screened. This approximation allows sparse matrix methods to be used, which can reduce the apparent computational scaling to O(N). Previously there were several simulation studies using this approximation for monodisperse suspensions. Here, we employ newly designed preconditioned iterative methods for both the computation of Brownian forces and the solution of linear systems, and consider the validity of this approximation in polydisperse suspensions. We evaluate the accuracy of the diagonal approximation method using an intracellular-like suspension. The diffusivities of particles obtained with this approximation are close to those with the original method. However, this approximation underestimates intermolecular correlated motions, which is a trade-off between accuracy and computing efficiency. The new method makes it possible to perform large-scale and long-time simulation with an approximate accounting of hydrodynamic interactions.

Ando, Tadashi; Chow, Edmond; Skolnick, Jeffrey

2013-09-01

30

Structure, function, and folding of phosphoglycerate kinase are strongly perturbed by macromolecular crowding.  

PubMed

We combine experiment and computer simulation to show how macromolecular crowding dramatically affects the structure, function, and folding landscape of phosphoglycerate kinase (PGK). Fluorescence labeling shows that compact states of yeast PGK are populated as the amount of crowding agents (Ficoll 70) increases. Coarse-grained molecular simulations reveal three compact ensembles: C (crystal structure), CC (collapsed crystal), and Sph (spherical compact). With an adjustment for viscosity, crowded wild-type PGK and fluorescent PGK are about 15 times or more active in 200 mg/ml Ficoll than in aqueous solution. Our results suggest a previously undescribed solution to the classic problem of how the ADP and diphosphoglycerate binding sites of PGK come together to make ATP: Rather than undergoing a hinge motion, the ADP and substrate sites are already located in proximity under crowded conditions that mimic the in vivo conditions under which the enzyme actually operates. We also examine T-jump unfolding of PGK as a function of crowding experimentally. We uncover a nonmonotonic folding relaxation time vs. Ficoll concentration. Theory and modeling explain why an optimum concentration exists for fastest folding. Below the optimum, folding slows down because the unfolded state is stabilized relative to the transition state. Above the optimum, folding slows down because of increased viscosity. PMID:20921368

Dhar, Apratim; Samiotakis, Antonios; Ebbinghaus, Simon; Nienhaus, Lea; Homouz, Dirar; Gruebele, Martin; Cheung, Margaret S

2010-10-12

31

Probing the Interplay of Size, Shape, and Solution Environment in Macromolecular Diffusion Using a Simple Refraction Experiment  

ERIC Educational Resources Information Center

The diffusion coefficient of polymers is a critical parameter in biomedicine, catalysis, chemical separations, nanotechnology, and other industrial applications. Here, measurement of macromolecular diffusion in solutions is described using a visually instructive, undergraduate-level optical refraction experiment based on Weiner's method. To…

Mankidy, Bijith D.; Coutinho, Cecil A.; Gupta, Vinay K.

2010-01-01

32

Gordon Research Conference on Dynamics of Macromolecular and Polyelectrolyte Solutions Held in Oxnard, California on 12-16 February 1990.  

National Technical Information Service (NTIS)

The Gordon Research Conference on 'Dynamics of Macromolecular and Polyelectrolyte Solutions' was held 12-16 February, 1990, at Casa Sirena Hotel, Oxnard, CA. There were ninety-one scientists participating, including thirty-four academics from the U.S.; tw...

L. J. Magid

1990-01-01

33

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

34

A MACROMOLECULAR REPEATING UNIT OF MITOCHONDRIAL STRUCTURE AND FUNCTION  

PubMed Central

A repeating particle associated with the cristae and the inner membrane of the external envelope has been recognized and characterized in beef heart mitochondria by correlated electron microscopic and biochemical studies. Many thousands (ca. 104 to 105) of these particles, disposed in regular arrays, are present in a single mitochondrion. The repeating particle, called the elementary particle (EP), consists of three parts: (1) a spherical or polyhedral head piece (80 to 100 A in diameter); (2) a cylindrical stalk (about 50 A long and 30 to 40 A wide); and (3) a base piece (40 x 110 A). The base pieces of the elementary particles form an integral part of the outer dense layers of the cristae. The elementary particles can be seen in electron micrographs of mitochondria in situ, of isolated mitochondria, and of submitochondrial particles with a complete electron transfer chain. Negative staining with phosphotungstate is only one of several techniques that can be used for reproducible demonstration of the repeating particles and underlying subunit organization of mitochondrial membranes. A particulate unit containing a complete electron transfer chain can be isolated from beef heart mitochondria. The isolated unit approximates in size that of the elementary particle in situ. The molecular weight of the particle in situ is calculated to be 1.3 x 106. Evidence is presented for identifying the isolated unit with the elementary particle visualized in situ. The elementary particle of the mitochondrion is believed to be a prototype of a class of functional particles or macromolecular assemblies of similar size found in association with membranes generally.

Fernandez-Moran, H.; Oda, T.; Blair, P. V.; Green, D. E.

1964-01-01

35

3DEM Loupe: Analysis of macromolecular dynamics using structures from electron microscopy.  

PubMed

Electron microscopy (EM) provides access to structural information of macromolecular complexes in the 3-20 Å resolution range. Normal mode analysis has been extensively used with atomic resolution structures and successfully applied to EM structures. The major application of normal modes is the identification of possible conformational changes in proteins. The analysis can throw light on the mechanism following ligand binding, protein-protein interactions, channel opening and other functional macromolecular movements. In this article, we present a new web server, 3DEM Loupe, which allows normal mode analysis of any uploaded EM volume using a user-friendly interface and an intuitive workflow. Results can be fully explored in 3D through animations and movies generated by the server. The application is freely available at http://3demloupe.cnb.csic.es. PMID:23671335

Nogales-Cadenas, R; Jonic, S; Tama, F; Arteni, A A; Tabas-Madrid, D; Vázquez, M; Pascual-Montano, A; Sorzano, C O S

2013-07-01

36

3DEM Loupe: analysis of macromolecular dynamics using structures from electron microscopy  

PubMed Central

Electron microscopy (EM) provides access to structural information of macromolecular complexes in the 3–20 Å resolution range. Normal mode analysis has been extensively used with atomic resolution structures and successfully applied to EM structures. The major application of normal modes is the identification of possible conformational changes in proteins. The analysis can throw light on the mechanism following ligand binding, protein–protein interactions, channel opening and other functional macromolecular movements. In this article, we present a new web server, 3DEM Loupe, which allows normal mode analysis of any uploaded EM volume using a user-friendly interface and an intuitive workflow. Results can be fully explored in 3D through animations and movies generated by the server. The application is freely available at http://3demloupe.cnb.csic.es.

Nogales-Cadenas, R.; Jonic, S.; Tama, F.; Arteni, A. A.; Tabas-Madrid, D.; Vazquez, M.; Pascual-Montano, A.; Sorzano, C. O. S.

2013-01-01

37

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

PubMed

X-ray free-electron laser (XFEL) sources enable the use of crystallography to solve three-dimensional macromolecular structures under native conditions and without 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 meaningful 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

2014-05-01

38

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.

Hattne, Johan; Echols, Nathaniel; Tran, Rosalie; Kern, Jan; Gildea, Richard J.; Brewster, Aaron S.; Alonso-Mori, Roberto; Glockner, Carina; Hellmich, Julia; Laksmono, Hartawan; Sierra, Raymond G.; Lassalle-Kaiser, Benedikt; Lampe, Alyssa; Han, Guangye; Gul, Sheraz; DiFiore, Dorte; 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, Sebastien; Messinger, Johannes; Zouni, Athina; Yano, Junko; Bergmann, Uwe; Yachandra, Vittal K.; Adams, Paul D.; Sauter, Nicholas K.

2014-01-01

39

Structure of Metaphase Chromosomes: A Role for Effects of Macromolecular Crowding  

PubMed Central

In metaphase chromosomes, chromatin is compacted to a concentration of several hundred mg/ml by mechanisms which remain elusive. Effects mediated by the ionic environment are considered most frequently because mono- and di-valent cations cause polynucleosome chains to form compact ?30-nm diameter fibres in vitro, but this conformation is not detected in chromosomes in situ. A further unconsidered factor is predicted to influence the compaction of chromosomes, namely the forces which arise from crowding by macromolecules in the surrounding cytoplasm whose measured concentration is 100–200 mg/ml. To mimic these conditions, chromosomes were released from mitotic CHO cells in solutions containing an inert volume-occupying macromolecule (8 kDa polyethylene glycol, 10.5 kDa dextran, or 70 kDa Ficoll) in 100 µM K-Hepes buffer, with contaminating cations at only low micromolar concentrations. Optical and electron microscopy showed that these chromosomes conserved their characteristic structure and compaction, and their volume varied inversely with the concentration of a crowding macromolecule. They showed a canonical nucleosomal structure and contained the characteristic proteins topoisomerase II? and the condensin subunit SMC2. These observations, together with evidence that the cytoplasm is crowded in vivo, suggest that macromolecular crowding effects should be considered a significant and perhaps major factor in compacting chromosomes. This model may explain why ?30-nm fibres characteristic of cation-mediated compaction are not seen in chromosomes in situ. Considering that crowding by cytoplasmic macromolecules maintains the compaction of bacterial chromosomes and has been proposed to form the liquid crystalline chromosomes of dinoflagellates, a crowded environment may be an essential characteristic of all genomes.

Hancock, Ronald

2012-01-01

40

Macromolecular Calculations in the XTAL System of Crystallographic Programs.  

National Technical Information Service (NTIS)

This project is concerned with the production of crystallographic computer codes for the solution and refinement of macromolecular crystal structures. The computer programs are being prepared within the context of an existing suite of crystallographic com...

J. M. Stewart

1988-01-01

41

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

42

Improving the accuracy of macromolecular structure refinement at 7 ? 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.

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

2012-01-01

43

The PDB_REDO server for macromolecular structure model optimization  

PubMed Central

The refinement and validation of a crystallographic structure model is the last step before the coordinates and the associated data are submitted to the Protein Data Bank (PDB). The success of the refinement procedure is typically assessed by validating the models against geometrical criteria and the diffraction data, and is an important step in ensuring the quality of the PDB public archive [Read et al. (2011 ?), Structure, 19, 1395–1412]. The PDB_REDO procedure aims for ‘constructive validation’, aspiring to consistent and optimal refinement parameterization and pro-active model rebuilding, not only correcting errors but striving for optimal interpretation of the electron density. A web server for PDB_REDO has been implemented, allowing thorough, consistent and fully automated optimization of the refinement procedure in REFMAC and partial model rebuilding. The goal of the web server is to help practicing crystallo­graphers to improve their model prior to submission to the PDB. For this, additional steps were implemented in the PDB_REDO pipeline, both in the refinement procedure, e.g. testing of resolution limits and k-fold cross-validation for small test sets, and as new validation criteria, e.g. the density-fit metrics implemented in EDSTATS and ligand validation as implemented in YASARA. Innovative ways to present the refinement and validation results to the user are also described, which together with auto-generated Coot scripts can guide users to subsequent model inspection and improvement. It is demonstrated that using the server can lead to substantial improvement of structure models before they are submitted to the PDB.

Joosten, Robbie P.; Long, Fei; Murshudov, Garib N.; Perrakis, Anastassis

2014-01-01

44

The study of macromolecular structure by pulsed NMR  

NASA Astrophysics Data System (ADS)

NMR has been widely used to determine chemical structure. The analysis of many important physical and physico-chemical properties such as molecular weight and mobility, the effect of crosslinking and entanglements and of solvents temperature, the role of crystalline regions and chain flexebility may be achieved very readily and simply these techniques. Once methods of analysis are understood and evaluated, they may serve only for the analysis of radiation effects but also for other forms of chemical treatment, the role of additives, orientation, and understanding and evaluation of important physical aspects, for which many of these polymers are intended. The use of pulsed NMR can also be used to evaluate radiation chemistry under different conditions, and it is expected that this knowledge could be extended to biological and medical systems, where a knowledge of the physical arrangements, mobility, entangled and other molecular properties and especially arrangement can be very important, yet difficult to measure.

Charlesby, Arthur

1995-06-01

45

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.

2013-01-01

46

Recovering a representative conformational ensemble from underdetermined macromolecular structural data.  

PubMed

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 the 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 diubiquitin, 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 diubiquitin, and revealed lesser-populated conformations that are preorganized for binding known diubiquitin 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

2013-11-01

47

Flexible torsion-angle noncrystallographic symmetry restraints for improved macromolecular structure refinement  

PubMed Central

One of the great challenges in refining macromolecular crystal structures is a low data-to-parameter ratio. Historically, knowledge from chemistry has been used to help to improve this ratio. When a macromolecule crystallizes with more than one copy in the asymmetric unit, the noncrystallographic symmetry relationships can be exploited to provide additional restraints when refining the working model. However, although globally similar, NCS-related chains often have local differences. To allow for local differences between NCS-related molecules, flexible torsion-based NCS restraints have been introduced, coupled with intelligent rotamer handling for protein chains, and are available in phenix.refine for refinement of models at all resolutions.

Headd, Jeffrey J.; Echols, Nathaniel; Afonine, Pavel V.; Moriarty, Nigel W.; Gildea, Richard J.; Adams, Paul D.

2014-01-01

48

? 13C of free and macromolecular aromatic structures in the murchison meteorite  

NASA Astrophysics Data System (ADS)

Analyses of the organic compounds in the Murchison meteorite have led to a greater understanding of the nature of extraterrestrial organic materials. However, the relationship between low and high molecular weight material remains poorly understood. To investigate this relationship, untreated Murchison was subjected to supercritical fluid extraction (SFE) to obtain the free organic components in the meteorite. Toluene and other volatile aromatic hydrocarbons dominated the extract, and the carbon isotopic composition of these molecules was determined by gas chromatography-isotope ratio-mass spectrometry (GCIRMS). ? 13C values of the aromatic hydrocarbons ranged from -28.8 to -5.8‰. These compounds displayed a 13C-enrichment with increasing carbon number suggesting an origin by cracking. The high molecular weight organic material in the meteorite was isolated and subjected to hydrous pyrolysis. This procedure produced a number of aromatic products, the majority of which were volatile aromatic hydrocarbons, particularly toluene. SFE was used to extract and successfully retain them. This enabled the first carbon isotopic analysis of this poorly understood material to be performed at the molecular level by GCIRMS. ? 13C values for aromatic pyrolysis products occupied a range from -24.6 to -5.6‰. The trend of 13C-enrichment with increasing carbon number, observed in the free compounds, was also evident in the macromolecular fragments. Furthermore, the organic fragments of the macromolecular material were consistently 13C-enriched when compared to structurally identical free molecules. This suggested that the free aromatic hydrocarbons in Murchison were produced by the preterrestrial degradation of the organic macromolecular material. This natural degradation event was extended by the hydrous pyrolysis experiment.

Sephton, M. A.; Pillinger, C. T.; Gilmour, I.

1998-05-01

49

Gas-phase processes and measurements of macromolecular properties in solution  

Microsoft Academic Search

Electrospray ionization mass spectrometry is increasingly applied to study protein behavior in solution, including characterization of their higher order structure, conformational dynamics and interactions with small ligands and other biopolymers. However, actual measurements of fundamental ionic parameters (mass and charge) take place in vacuum, and an array of gas phase processes occurring prior to protein ion detection and characterization may

Rinat R. Abzalimov; Agya K. Frimpong; Igor A. Kaltashov

2006-01-01

50

HBAT: a complete package for analysing strong and weak hydrogen bonds in macromolecular crystal structures.  

PubMed

The program HBAT is a tool to automate the analysis of potential hydrogen bonds and similar type of weak interactions like halogen bonds and non-canonical interactions in macromolecular structures, available in Brookhaven Protein Database (PDB) file format. HBAT is written using PERL and TK languages. The program generates an MSOFFICE Excel compatible output file for statistical analysis. HBAT identify potential interactions based on geometrical criteria. A series of analysis reports like frequency tables, geometry distribution tables, furcations list are generated. A user friendly GUI offers freedom to select several parameters and options. Graphviz based visualization of hydrogen bond networks in 2D helps to study the cooperativity and anticooperativity geometry in hydrogen bond. HBAT supports post docking interaction analysis between PDB files for any target/receptor (in PDB files) and docked ligands/poses (in SDF). This tool can be implemented in active site interaction analysis, structure based drug design and molecular dynamics simulations. PMID:18467777

Tiwari, Abhishek; Panigrahi, Sunil K

2007-01-01

51

A 3D Image Filter for Parameter-Free Segmentation of Macromolecular Structures from Electron Tomograms  

PubMed Central

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.

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

2012-01-01

52

Methods to refine macromolecular structures in cases of severe diffraction anisotropy.  

PubMed

Diffraction anisotropy is characterized by variation in diffraction quality with reciprocal lattice direction. In the example presented here, diffraction extended to 2.1 Å resolution along a* and c* directions but only to 3.0 Å along the b* direction. Severe anisotropy such as this is often associated with lack of detail in electron density maps, stalled model improvement, and poor refinement statistics. Published methods for overcoming these difficulties have been combined and implemented in the diffraction anisotropy server. Specifically, the server offers information to diagnose the degree of anisotropy, and then applies ellipsoidal resolution boundaries, anisotropic scaling, and B-factor sharpening to the data set to compensate for the deleterious effects of diffraction anisotropy. Here, I offer advice on implementing these methods to facilitate refinement of macromolecular structures in cases of severely anisotropic data. PMID:24203335

Sawaya, Michael R

2014-01-01

53

New computational tools for H/D determination in macromolecular structures from neutron data.  

PubMed

Two new computational methods dedicated to neutron crystallography, called n-FreeLunch and DNDM-NDM, have been developed and successfully tested. The aim in developing these methods is to determine hydrogen and deuterium positions in macromolecular structures by using information from neutron density maps. Of particular interest is resolving cases in which the geometrically predicted hydrogen or deuterium positions are ambiguous. The methods are an evolution of approaches that are already applied in X-ray crystallography: extrapolation beyond the observed resolution (known as the FreeLunch procedure) and a difference electron-density modification (DEDM) technique combined with the electron-density modification (EDM) tool (known as DEDM-EDM). It is shown that the two methods are complementary to each other and are effective in finding the positions of H and D atoms in neutron density maps. PMID:21041931

Siliqi, Dritan; Caliandro, Rocco; Carrozzini, Benedetta; Cascarano, Giovanni Luca; Mazzone, Annamaria

2010-11-01

54

Biological Macromolecular Structures Data from the RCSB Protein Data Bank (RCSB PDB)  

DOE Data Explorer

The Research Collaboratory for Structural Bioinformatics (RCSB) is a non-profit consortium that works to improve understanding of the function of biological systems through the study of the 3-D structure of biological macromolecules. The RCSB PDB is one of three sites serving as deposition, data processing, and distribution sites of the Protein Data Bank Archive. Each site provides its own view of the primary data, thus providing a variety of tools and resources for the global community. RCSB is also the official keeper for the PDB archive, with sole access authority to the PDB archive directory structure and contents. The RCSB PDB Information Portal for Biological Macromolecular Structures offers online tools for search and retrieval, for visualizing structures, for depositing, validating, or downloading data, news and highlights, a discussion forum, and links to other areas of related research. The PDB archive is a repository of atomic coordinates and other information describing proteins and other important biological macromolecules. Structural biologists use methods such as X-ray crystallography, NMR spectroscopy, and cryo-electron microscopy to determine the location of each atom relative to each other in the molecule. They then deposit this information, which is then annotated and publicly released into the archive by the wwPDB. Results can be viewed as 3-D images or models.

55

MetalPDB: a database of metal sites in biological macromolecular structures  

PubMed Central

We present here MetalPDB (freely accessible at http://metalweb.cerm.unifi.it), a novel resource aimed at conveying the information available on the three-dimensional (3D) structures of metal-binding biological macromolecules in a consistent and effective manner. This is achieved through the systematic and automated representation of metal-binding sites in proteins and nucleic acids by way of Minimal Functional Sites (MFSs). MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure embedding the site(s), and are the central objects of MetalPDB design. MFSs are grouped into equistructural (broadly defined as sites found in corresponding positions in similar structures) and equivalent sites (equistructural sites that contain the same metals), allowing users to easily analyse similarities and variations in metal–macromolecule interactions, and to link them to functional information. The web interface of MetalPDB allows access to a comprehensive overview of metal-containing biological structures, providing a basis to investigate the basic principles governing the properties of these systems. MetalPDB is updated monthly in an automated manner.

Andreini, Claudia; Cavallaro, Gabriele; Lorenzini, Serena; Rosato, Antonio

2013-01-01

56

MetalPDB: a database of metal sites in biological macromolecular structures.  

PubMed

We present here MetalPDB (freely accessible at http://metalweb.cerm.unifi.it), a novel resource aimed at conveying the information available on the three-dimensional (3D) structures of metal-binding biological macromolecules in a consistent and effective manner. This is achieved through the systematic and automated representation of metal-binding sites in proteins and nucleic acids by way of Minimal Functional Sites (MFSs). MFSs are 3D templates that describe the local environment around the metal(s) independently of the larger context of the macromolecular structure embedding the site(s), and are the central objects of MetalPDB design. MFSs are grouped into equistructural (broadly defined as sites found in corresponding positions in similar structures) and equivalent sites (equistructural sites that contain the same metals), allowing users to easily analyse similarities and variations in metal-macromolecule interactions, and to link them to functional information. The web interface of MetalPDB allows access to a comprehensive overview of metal-containing biological structures, providing a basis to investigate the basic principles governing the properties of these systems. MetalPDB is updated monthly in an automated manner. PMID:23155064

Andreini, Claudia; Cavallaro, Gabriele; Lorenzini, Serena; Rosato, Antonio

2013-01-01

57

Chemical composition and structural features of the macromolecular components of plantation Acacia mangium wood.  

PubMed

The wood of Acacia mangium, a prominent fast-growing plantation species used in the pulp-and-paper industry and, so far, poorly investigated for its chemical structure, was submitted to a detailed characterization of its main macromolecular components. Lignin (28% wood weight) isolated by mild acidolysis and characterized by permanganate oxidation, 1H and 13C NMR, and GPC, showed a very low content of syringylpropane-derived units (S:G:H of 48:49:3), a high degree of condensation, a low content of beta-O-4 ( approximately 0.40-0.43 per C6) structures, and a Mw of 2230. Glucuronoxylan (14% wood weight) isolated by alkaline (KOH) or by dimethyl sulfoxide extraction was characterized by methylation analysis, 1H NMR, and GPC. About 10% of the xylopyranose (Xylp) units constituting the linear backbone were substituted at O-2 with 4-O-methylglucuronic acid residues. Almost half of the Xylp units (45%) were O-2 (18%), O-3 (24%) or O-2,3 (3%) acetylated. X-ray diffraction analysis of cellulose (46% wood weight), isolated according to the Kürschner-Hoffer method, showed a degree of crystallinity of 67.6%. PMID:16190642

Pinto, Paula C; Evtuguin, Dmitry V; Pascoal Neto, Carlos

2005-10-01

58

IMAGINE: first neutron protein structure and new capabilities for neutron macromolecular crystallography  

SciTech Connect

We report the first high resolution neutron protein structure of perdeuterated rubredoxin from Pyrococcus furiosus (PfRd) determined using the new IMAGINE macromolecular neutron crystallography instrument at the Oak Ridge National Laboratory. Neutron diffraction data extending to 1.65 resolution were collected from a relatively small 0.7 mm3 PfRd crystal using 2.5 days (60 h) of beam time. The refined structure contains 371 out of 391, or 95%, of the deuterium atoms of the protein, and 58 solvent molecules. The IMAGINE instrument is designed to provide neutron data at or near atomic resolutions (1.5 ) from crystals with volume < 1.0 mm3 and with unit cell edges < 100 . Beam line features include elliptical focusing mirrors that deliver 3x107 n s-1 cm-2 into a 3.5 x 2.0 mm2 focal spot at the sample position, and variable short and long wavelength cutoff optics that provide automated exchange between multiple wavelength configurations ( min=2.0 , 2.8 , 3.3 - max =3.0 , 4.0 , 4.5 , ~20 ). Notably, the crystal used to collect this PfRd data is 5-10 times smaller than has been previously reported.

Munshi, Parthapratim [ORNL] [ORNL; Myles, Dean A A [ORNL] [ORNL; Robertson, Lee [ORNL] [ORNL; Stoica, Alexandru Dan [ORNL] [ORNL; Crow, Lowell [ORNL] [ORNL; Kovalevskyi, Andrii Y [ORNL] [ORNL; Koritsanszky, Tibor S [ORNL] [ORNL; Chakoumakos, Bryan C [ORNL] [ORNL; Blessing, Robert [Hauptman-Woodward Medical Research Institute] [Hauptman-Woodward Medical Research Institute; Meilleur, Flora [ORNL] [ORNL

2013-01-01

59

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

60

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

61

An apparatus for the study of macromolecular solutions by the Kerr effect  

Microsoft Academic Search

Solutions of macromolecules exhibit double refraction when subjected to an electric field (Kerr effect). A study of this effect may be made by applying a pulse of rectangular shape to such solutions. Measurement of the magnitude of the birefringence and of its rise and fall enables information on molecular parameters to be obtained and in particular values of molecular relaxation

H G Jerrard; C L Riddiford; P Ingram

1969-01-01

62

The IMAGINE instrument: first neutron protein structure and new capabilities for neutron macromolecular crystallography.  

PubMed

The first high-resolution neutron protein structure of perdeuterated rubredoxin from Pyrococcus furiosus (PfRd) determined using the new IMAGINE macromolecular neutron crystallography instrument at the Oak Ridge National Laboratory is reported. Neutron diffraction data extending to 1.65?Å resolution were collected from a relatively small 0.7?mm(3) PfRd crystal using 2.5?d (60?h) of beam time. The refined structure contains 371 out of 391, or 95%, of the D atoms of the protein and 58 solvent molecules. The IMAGINE instrument is designed to provide neutron data at or near atomic resolution (1.5?Å) from crystals with volume <1.0?mm(3) and with unit-cell edges <100?Å. Beamline features include novel elliptical focusing mirrors that deliver neutrons into a 2.0 × 3.2?mm focal spot at the sample position with full-width vertical and horizontal divergences of 0.5 and 0.6°, respectively. Variable short- and long-wavelength cutoff optics provide automated exchange between multiple-wavelength configurations (?min = 2.0, 2.8, 3.3?Å to ?max = 3.0, 4.0, 4.5, ?20?Å). These optics produce a more than 20-fold increase in the flux density at the sample and should help to enable more routine collection of high-resolution data from submillimetre-cubed crystals. Notably, the crystal used to collect these PfRd data was 5-10 times smaller than those previously reported. PMID:24100333

Meilleur, Flora; Munshi, Parthapratim; Robertson, Lee; Stoica, Alexandru D; Crow, Lowell; Kovalevsky, Andrey; Koritsanszky, Tibor; Chakoumakos, Bryan C; Blessing, Robert; Myles, Dean A A

2013-10-01

63

SedNMR: a web tool for optimizing sedimentation of macromolecular solutes for SSNMR.  

PubMed

We have proposed solid state NMR (SSNMR) of sedimented solutes as a novel approach to sample preparation for biomolecular SSNMR without crystallization or other sample manipulations. The biomolecules are confined by high gravity--obtained by centrifugal forces either directly in a SSNMR rotor or in a ultracentrifugal device--into a hydrated non-crystalline solid suitable for SSNMR investigations. When gravity is removed, the sample reverts to solution and can be treated as any solution NMR sample. We here describe a simple web tool to calculate the relevant parameters for the success of the experiment. PMID:24243317

Ferella, Lucio; Luchinat, Claudio; Ravera, Enrico; Rosato, Antonio

2013-12-01

64

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 at the OMM. 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.

Marcey, David

2006-05-17

65

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

66

Structure Solution - An Overview  

NASA Astrophysics Data System (ADS)

The structure solution process consists of a series of steps, each requiring decisions and each depending upon the previous ones having been performed correctly. The preliminary steps involve selecting the best sample, choosing the most appropriate radiation, collecting the data, indexing the pattern, determining the most probable space group(s), and estimating the profile parameters. If extracted intensities are to be used for structure solution, something must be done about the overlapping reflections. They can be equipartitioned, or, if necessary, more sophisticated approaches can be applied to improve the partitioning. At this point, the structure solution algorithm most appropriate for the material and the data must be chosen and applied. Finally, the (partial) structural model has to be completed and refined. The art of structure determination from powder diffraction data lies in finding a viable path through the maze of possibilities.

McCusker, Lynne B.; Baerlocher, Christian

67

NMR (Nuclear Magnetic Resonance) and Macromolecular Migration in a Melt or in Concentrated Solutions.  

National Technical Information Service (NTIS)

The purpose of this paper is to analyse 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 frequen...

J. P. C. Addad

1983-01-01

68

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

69

An NMR study of macromolecular aggregation in a model polymer-surfactant solution  

Microsoft Academic Search

A model complex-forming nonionic polymer-anionic surfactant system in aqueous solution has been studied at different surfactant concentrations. Using pulsed-field-gradient diffusion NMR spectroscopy, we obtain the self-diffusion coefficients of poly(ethylene glycol) (PEO) and sodium dodecyl sulfate (SDS) simultaneously and as a function of SDS concentration. In addition, we obtain NMR relaxation rates and chemical shifts as a function of SDS concentration.

Suliman Barhoum; Anand Yethiraj

2010-01-01

70

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

71

An NMR study of macromolecular aggregation in a model polymer-surfactant solution.  

PubMed

A model complex-forming nonionic polymer-anionic surfactant system in aqueous solution has been studied at different surfactant concentrations. Using pulsed-field-gradient diffusion NMR spectroscopy, we obtain the self-diffusion coefficients of poly(ethylene glycol) (PEO) and sodium dodecyl sulfate (SDS) simultaneously and as a function of SDS concentration. In addition, we obtain NMR relaxation rates and chemical shifts as a function of SDS concentration. Within the context of a simple model, our experimental results yield the onset of aggregation of SDS on PEO chains (CAC=3.5 mM), a crossover concentration (C(2)=60 mM) which signals a sharp change in relaxation behavior, as well as an increase in free surfactant concentration and a critical concentration (C(m)=145 mM) which signals a distinct change in diffusion behavior and a crossover to a solution containing free micelles. C(m) also marks the concentration above which obstruction effects are definitely important. In addition, we obtain the concentration of SDS in monomeric form and in the form of free micelles, as well as the average number of SDS molecules in a PEO-SDS aggregate (N(Aggr)). Taken together, our results suggests continuous changes in the aggregation phenomenon over much of the concentration but with three distinct concentrations that signal changes in the nature of the aggregates. PMID:20095711

Barhoum, Suliman; Yethiraj, Anand

2010-01-14

72

An NMR study of macromolecular aggregation in a model polymer-surfactant solution  

NASA Astrophysics Data System (ADS)

A model complex-forming nonionic polymer-anionic surfactant system in aqueous solution has been studied at different surfactant concentrations. Using pulsed-field-gradient diffusion NMR spectroscopy, we obtain the self-diffusion coefficients of poly(ethylene glycol) (PEO) and sodium dodecyl sulfate (SDS) simultaneously and as a function of SDS concentration. In addition, we obtain NMR relaxation rates and chemical shifts as a function of SDS concentration. Within the context of a simple model, our experimental results yield the onset of aggregation of SDS on PEO chains (CAC=3.5 mM), a crossover concentration (C2=60 mM) which signals a sharp change in relaxation behavior, as well as an increase in free surfactant concentration and a critical concentration (Cm=145 mM) which signals a distinct change in diffusion behavior and a crossover to a solution containing free micelles. Cm also marks the concentration above which obstruction effects are definitely important. In addition, we obtain the concentration of SDS in monomeric form and in the form of free micelles, as well as the average number of SDS molecules in a PEO-SDS aggregate (NAggr). Taken together, our results suggests continuous changes in the aggregation phenomenon over much of the concentration but with three distinct concentrations that signal changes in the nature of the aggregates.

Barhoum, Suliman; Yethiraj, Anand

2010-01-01

73

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

74

Asphalts and asphaltenes: Macromolecular structure, precipitation properties, and flow in porous media  

NASA Astrophysics Data System (ADS)

Depending on rock and fluid properties, more than 50% of reservoir oil in place is normally produced by enhanced oil recovery (EOR) methods. Among the EOR techniques, miscible flooding is one of the most efficient and widely-used methods. However, this method can suffer from the formation and precipitation of asphalt aggregates. In addition, asphalt deposition is also a major hindrance to heavy oil production, and even primary recovery operations. Asphalt deposition can alter the reservoir rock properties, fluid saturation distribution, fluid flow properties, and eventually the ultimate oil recovery. The shortage of studies on the macromolecular structure and growth mechanisms of asphalt particles is the main reason for the unsuccessful modeling of their precipitation properties. The equivocal behavior of asphalt under some specific conditions could be the other reason. In this research we look at the problem of asphalt formation, flow, and precipitation from three different angles. We analyze extensive small-angle X-ray and neutron scattering data, precipitation data, and molecular weight distribution measurements, and show that they all suggest conclusively that asphalts and asphaltenes are fractal aggregates, and their growth mechanisms are diffusion-limited particle (DLP) and diffusion-limited cluster-cluster (DLCC) aggregation processes. These results lead us to development of a scaling equation of state for predicting asphalt precipitation properties, such as its onset and amount of precipitation. Another result of our study is an analytical equation for modeling the molecular weight distribution of asphalt and asphaltene aggregates. In addition, asphalt phase behavior in miscible and immiscible injections is studied. The effect of the governing thermodynamic factors, such as the pressure, temperature, and composition of the oil and precipitation agents, on the asphalt aggregation and disaggregation processes are investigated. Finally, a model is developed to study the flow of an asphalt-containing oil through a reservoir. A large volume of the field data are analyzed for delineating the asphalt precipitation and release mechanisms in the reservoir and the resulting patterns of the permeability alteration.

Rassamdana, Hossein

75

Macromolecular structures probed by combining single-shot free-electron laser diffraction with synchrotron coherent X-ray imaging  

NASA Astrophysics Data System (ADS)

Nanostructures formed from biological macromolecular complexes utilizing the self-assembly properties of smaller building blocks such as DNA and RNA hold promise for many applications, including sensing and drug delivery. New tools are required for their structural characterization. Intense, femtosecond X-ray pulses from X-ray free-electron lasers enable single-shot imaging allowing for instantaneous views of nanostructures at ambient temperatures. When combined judiciously with synchrotron X-rays of a complimentary nature, suitable for observing steady-state features, it is possible to perform ab initio structural investigation. Here we demonstrate a successful combination of femtosecond X-ray single-shot diffraction with an X-ray free-electron laser and coherent diffraction imaging with synchrotron X-rays to provide an insight into the nanostructure formation of a biological macromolecular complex: RNA interference microsponges. This newly introduced multimodal analysis with coherent X-rays can be applied to unveil nano-scale structural motifs from functional nanomaterials or biological nanocomplexes, without requiring a priori knowledge.

Gallagher-Jones, Marcus; Bessho, Yoshitaka; Kim, Sunam; Park, Jaehyun; Kim, Sangsoo; Nam, Daewoong; Kim, Chan; Kim, Yoonhee; Noh, Do Young; Miyashita, Osamu; Tama, Florence; Joti, Yasumasa; Kameshima, Takashi; Hatsui, Takaki; Tono, Kensuke; Kohmura, Yoshiki; Yabashi, Makina; Hasnain, S. Samar; Ishikawa, Tetsuya; Song, Changyong

2014-05-01

76

Macromolecular structures probed by combining single-shot free-electron laser diffraction with synchrotron coherent X-ray imaging.  

PubMed

Nanostructures formed from biological macromolecular complexes utilizing the self-assembly properties of smaller building blocks such as DNA and RNA hold promise for many applications, including sensing and drug delivery. New tools are required for their structural characterization. Intense, femtosecond X-ray pulses from X-ray free-electron lasers enable single-shot imaging allowing for instantaneous views of nanostructures at ambient temperatures. When combined judiciously with synchrotron X-rays of a complimentary nature, suitable for observing steady-state features, it is possible to perform ab initio structural investigation. Here we demonstrate a successful combination of femtosecond X-ray single-shot diffraction with an X-ray free-electron laser and coherent diffraction imaging with synchrotron X-rays to provide an insight into the nanostructure formation of a biological macromolecular complex: RNA interference microsponges. This newly introduced multimodal analysis with coherent X-rays can be applied to unveil nano-scale structural motifs from functional nanomaterials or biological nanocomplexes, without requiring a priori knowledge. PMID:24786694

Gallagher-Jones, Marcus; Bessho, Yoshitaka; Kim, Sunam; Park, Jaehyun; Kim, Sangsoo; Nam, Daewoong; Kim, Chan; Kim, Yoonhee; Noh, Do Young; Miyashita, Osamu; Tama, Florence; Joti, Yasumasa; Kameshima, Takashi; Hatsui, Takaki; Tono, Kensuke; Kohmura, Yoshiki; Yabashi, Makina; Hasnain, S Samar; Ishikawa, Tetsuya; Song, Changyong

2014-01-01

77

Multiscale simulations of dilute-solution macromolecular dynamics in macroscopic and microscopic geometries  

NASA Astrophysics Data System (ADS)

A Brownian model of DNA is developed and shown to give results in quantitative agreement with available equilibrium and non-equilibrium experimental data. A fast, accurate method of calculating the Langevin forces on the molecule is presented, as well as a semi-implicit stochastic integration scheme which allows for the use of reasonable time steps. A new method is developed for the simulation of polymer dynamics in macroscopic devices. The method involves a splitting of the diffusion equation into internal configuration and convective fluxes. The internal configuration of the microstructure is evolved via stochastic simulation to give a delta-function representation of the distribution function. The convective update of the distribution function is performed in an orthogonal polynomial representation, taking advantage of the natural hierarchy of length scales present in the problem. We find that convective update can performed accurately by considering only the large length scale contributions. A general method is developed for dynamic simulations of macromolecules in confined geometries. At equilibrium, we examine the stretch, diffusivity and relaxation time of DNA as a function of channel width and molecular weight. The ratio of these properties to their free-solution values form master curves when plotted against Sb/H. Scaling laws are obtained for highly confined chains. In pressure-driven flow, the DNA chains migrate toward the channel centerline in agreement with well-known experimental observations. The thickness of the resulting hydrodynamic depletion layer increases with molecular weight at constant flow strength; higher molecular weight chains therefore move with a higher average axial velocity than lower molecular weight chains. A simple kinetic theory dumbbell model of a confined flexible polymer correctly predicts the trends observed in the detailed simulations. We also examine the steady-state stretch of DNA chains as a function of channel width and flow strength. The flow strength needed to stretch a highly confined chain away from its equilibrium length is shown to increase with decreasing channel width, independent of molecular weight; this is fairly well-explained using a simple blob picture.

Jendrejack, Richard Martin

78

Solution structure of ?-conotoxin SI  

Microsoft Academic Search

The nuclear magnetic resonance solution structure of ?-conotoxin SI has been determined at pH 4.2. The 36 lowest energy structures show that ?-conotoxin SI exists in a single major solution conformation and is stabilized by six hydrogen bonds. Comparisons are made between the SI solution structure and the solution and crystal structures of ?-conotoxin GI. Surprisingly, a high degree of

Andrew J. Benie; David Whitford; Balazs Hargittai; George Barany; Robert W. Janes

2000-01-01

79

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

80

Towards macromolecular architectures of corannulene.  

PubMed

In an attempt to introduce corannulene chemistry to macromolecular science, my research program is dedicated to synthetic strategies leading to corannulene-based polymers with interesting architectures and properties. In this brief account, I will discuss the synthesis of a variety of corannulene-based building blocks (monomers) and their utility in the preparation of a wide range of corannulene-rich macromolecular structures. PMID:22054134

Stuparu, Mihaiela C

2011-01-01

81

Macromolecular crowding effects on two homologs of ribosomal protein s16: protein-dependent structural changes and local interactions.  

PubMed

Proteins function in cellular environments that are crowded with biomolecules, and in this reduced available space, their biophysical properties may differ from those observed in dilute solutions in vitro. Here, we investigated the effects of a synthetic macromolecular crowding agent, dextran 20, on the folded states of hyperthermophilic (S16Thermo) and mesophilic (S16Meso) homologs of the ribosomal protein S16. As expected for an excluded-volume effect, the resistance of the mesophilic protein to heat-induced unfolding increased in the presence of dextran 20, and chemical denaturation experiments at different fixed temperatures showed the macromolecular crowding effect to be temperature-independent. Förster resonance energy transfer experiments show that intramolecular distances between an intrinsic Trp residue and BODIPY-labeled S16Meso depend on the level of the crowding agent. The BODIPY group was attached at three specific positions in S16Meso, allowing measurements of three intraprotein distances. All S16Meso variants exhibited a decrease in the average Trp-BODIPY distance at up to 100 mg/mL dextran 20, whereas the changes in distance became anisotropic (one distance increased, two distances decreased) at higher dextran concentrations. In contrast, the two S16Thermo mutants did not show any changes in Trp-BODIPY distances upon increase of dextran 20 concentrations. It should be noted that the fluorescence quantum yields and lifetimes of BODIPY attached to the two S16 homologs decreased gradually in the presence of dextran 20. To investigate the origin of this decrease, we studied the BODIPY quantum yield in three protein variants in the presence of a tyrosine-labeled dextran. The experiments revealed distinct tyrosine quenching behaviors of BODIPY in the three variants, suggesting a dynamic local interaction between dextran and one particular S16 variant. PMID:25028882

Mikaelsson, Therese; Adén, Jörgen; Wittung-Stafshede, Pernilla; Johansson, Lennart B-Å

2014-07-15

82

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

83

MACROMOLECULAR ABSORPTION  

PubMed Central

The immature small intestine of neonatal mammals is permeable to gamma globulins as a source of passive immunity. Allegedly, macromolecular absorption ceases when the epithelial cell membrane matures. However, some evidence exists that adult animals retain a limited capacity to transport antigenic and biologically active quantities of large molecules. In this study, the mechanism of absorption of the tracer protein, horseradish peroxidase (HRP), was tested in neonatal and adult rat gut sacs. Transport into serosal fluid was quantitated by enzymatic assay and monitored morphologically by histochemical techniques. A greater transport of HRP was noted in the adult jejunum compared to adult ileum and neonatal intestine. Morphologically, the uptake mechanism in adult intestine was similar to the endocytosis previously reported in neonatal animals Like other endocytotic processes, HRP uptake in adult rats is an energy-dependent process as determined by metabolic inhibitors and temperature-controlled studies. An understanding of the mechanism whereby macromolecules are bound to intestinal membranes and engulfed by them is necessary before the action of physiologic macromolecules such as enterotoxins can be appreciated.

Walker, W. A.; Cornell, R.; Davenport, L. M.; Isselbacher, K. J.

1972-01-01

84

Self-consistent treatment of the local dielectric permittivity and electrostatic potential in solution for polarizable macromolecular force fields.  

PubMed

A self-consistent method is presented for the calculation of the local dielectric permittivity and electrostatic potential generated by a solute of arbitrary shape and charge distribution in a polar and polarizable liquid. The structure and dynamics behavior of the liquid at the solute/liquid interface determine the spatial variations of the density and the dielectric response. Emphasis here is on the treatment of the interface. The method is an extension of conventional methods used in continuum protein electrostatics, and can be used to estimate changes in the static dielectric response of the liquid as it adapts to charge redistribution within the solute. This is most relevant in the context of polarizable force fields, during electron structure optimization in quantum chemical calculations, or upon charge transfer. The method is computationally efficient and well suited for code parallelization, and can be used for on-the-fly calculations of the local permittivity in dynamics simulations of systems with large and heterogeneous charge distributions, such as proteins, nucleic acids, and polyelectrolytes. Numerical calculation of the system free energy is discussed for the general case of a liquid with field-dependent dielectric response. PMID:22920098

Hassan, Sergio A

2012-08-21

85

Pathological Crystallography: Case Studies of Several Unusual Macromolecular Crystals  

SciTech Connect

Although macromolecular crystallography is rapidly becoming largely routine owing to advances in methods of data collection, structure solution and refinement, difficult cases are still common. To remind structural biologists about the kinds of crystallographic difficulties that might be encountered, case studies of several successfully completed structure determinations that utilized less than perfect crystals are discussed here. The structure of the proteolytic domain of Archaeoglobus fulgidus Lon was solved with crystals that contained superimposed orthorhombic and monoclinic lattices, a case not previously described for proteins. Another hexagonal crystal form of this protein exhibited an unusually high degree of non-isomorphism. Crystals of A. fulgidus Rio1 kinase exhibited both pseudosymmetry and twinning. Ways of identifying the observed phenomena and approaches to solving and refining macromolecular structures when only less than perfect crystals are available are discussed here.

Dauter,Z.; Botos, I.; LaRonde-LeBlanc, N.; Wlodawer, A.

2005-01-01

86

Validation of metal-binding sites in macromolecular structures with the CheckMyMetal web server.  

PubMed

Metals have vital roles in both the mechanism and architecture of biological macromolecules. Yet structures of metal-containing macromolecules in which metals are misidentified and/or suboptimally modeled are abundant in the Protein Data Bank (PDB). This shows the need for a diagnostic tool to identify and correct such modeling problems with metal-binding environments. The CheckMyMetal (CMM) web server (http://csgid.org/csgid/metal_sites/) is a sophisticated, user-friendly web-based method to evaluate metal-binding sites in macromolecular structures using parameters derived from 7,350 metal-binding sites observed in a benchmark data set of 2,304 high-resolution crystal structures. The protocol outlines how the CMM server can be used to detect geometric and other irregularities in the structures of metal-binding sites, as well as how it can alert researchers to potential errors in metal assignment. The protocol also gives practical guidelines for correcting problematic sites by modifying the metal-binding environment and/or redefining metal identity in the PDB file. Several examples where this has led to meaningful results are described in the ANTICIPATED RESULTS section. CMM was designed for a broad audience--biomedical researchers studying metal-containing proteins and nucleic acids--but it is equally well suited for structural biologists validating new structures during modeling or refinement. The CMM server takes the coordinates of a metal-containing macromolecule structure in the PDB format as input and responds within a few seconds for a typical protein structure with 2-5 metal sites and a few hundred amino acids. PMID:24356774

Zheng, Heping; Chordia, Mahendra D; Cooper, David R; Chruszcz, Maksymilian; Müller, Peter; Sheldrick, George M; Minor, Wladek

2014-01-01

87

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.

2006-01-25

88

Microbatch macromolecular crystallization in micropipettes  

NASA Astrophysics Data System (ADS)

A microbatch crystallization method suitable for macromolecular crystal growth is described. Solutions in the 1 ?l range are set up in micropipettes with very small inner diameter. The packaging is robust, compact and neat. Surface area of solution exposed to the atmosphere is much smaller than in a hanging drop vapor diffusion experiment. Small sample volumes make the packaging ideal for screening experiments, but crystals large enough for diffraction studies can be grown in, and recovered from, the micropipettes.

Luft, Joseph R.; Rak, Dawn M.; DeTitta, George T.

1999-01-01

89

iDC: A comprehensive toolkit for the analysis of residual dipolar couplings for macromolecular structure determination.  

PubMed

Measurement of residual dipolar couplings (RDCs) has become an important method for the determination and validation of protein or nucleic acid structures by NMRf spectroscopy. A number of toolkits have been devised for the handling of RDC data which run in the Linux/Unix operating environment and require specifically formatted input files. The outputs from these programs, while informative, require format modification prior to the incorporation of this data into commonly used personal computer programs for manuscript preparation. To bridge the gap between analysis and publication, an easy-to-use, comprehensive toolkit for RDC analysis has been created, iDC. iDC is written for the WaveMetrics Igor Pro mathematics program, a widely used graphing and data analysis software program that runs on both Windows PC and Mac OS X computers. Experimental RDC values can be loaded into iDC using simple data formats accessible to Igor's tabular data function. The program can perform most useful RDC analyses, including alignment tensor estimation from a histogram of RDC occurrence versus values and order tensor analysis by singular value decomposition (SVD). SVD analysis can be performed on an entire structure family at once, a feature missing in other applications of this kind. iDC can also import from and export to several different commonly used programs for the analysis of RDC data (DC, PALES, REDCAT) and can prepare formatted files for RDC-based refinement of macromolecular structures using XPLOR-NIH, CNS and ARIA. The graphical user interface provides an easy-to-use I/O for data, structures and formatted outputs. PMID:16791737

Wei, Yufeng; Werner, Milton H

2006-05-01

90

Do ionic charges in ESI MS provide useful information on macromolecular structure?  

Microsoft Academic Search

Multiple charging is an intrinsic feature of electrospray ionization (ESI) of macromolecules. While multiple factors influence\\u000a the appearance of protein ion charge state distributions in ESI mass spectra, physical dimensions of protein molecules in\\u000a solution are the major determinants of the extent of multiple charging. This article reviews the information that can be obtained\\u000a by analyzing ionic charge state distributions

Igor A. Kaltashov; Rinat R. Abzalimov

2008-01-01

91

The effects of (macro)molecular structure on hydrophilic surface modification of polypropylene membranes via entrapment  

Microsoft Academic Search

Entrapment of a variety of ethyleneoxide-containing substances from nonpolar solutions into polypropylene (PP) microfiltration membrane surface for hydrophilic modification was studied. The results from gravimetric weight gain, surface characterization by contact angle measurements and ATR-IR spectroscopy, water flux measurements and protein adsorption revealed that poly(ethylene glycol)s (PEGs) were ineffective, while many nonionic amphiphilic substances, especially some tri-block copolymers of poly(ethyleneoxide)

Haofei Guo; Mathias Ulbricht

2010-01-01

92

Solvation structure, thermodynamics, and conformational dependence of alanine dipeptide in aqueous solution analyzed with reference interaction site model theory  

Microsoft Academic Search

With the CHARMM22 (Chemistry at Harvard Macromolecular Mechanics) all-atom nonbonded potential parameters for alanine dipeptide solute and the transferable intermolecular potential model water for the solvent, the reference interaction site model (RISM) integral equations with the hypernetted chain closure are solved to obtain all the atomic solvent-solute radial distribution functions. The solvation structures of alanine dipeptide in its seven conformations:

Qizhi Cui; Vedene H. Smith

2003-01-01

93

Macromolecular Structure Modeling from 3DEM Using VolRover 2.01  

PubMed Central

We report several tools for 3DEM structure identification and model-based refinement developed by our research group and implemented in our in-house software package, VolRover. For viral density maps with icosahedral symmetry, we segment the capsid, polymeric and monomeric subunits using segmentation techniques based on symmetry detection and fast marching. For large biomolecules without symmetry information, we use a multi-seeded fast-marching method to segment meaningful substructures. In either case, we subject the resulting segmented subunit to secondary structure detection when the EM resolution is sufficiently high, and rigid-body fitting when the corresponding crystal structure is available. Secondary structure elements are identified by our volume- and boundary-based skeletonization methods as well as a new method, currently in development, based on solving the grassfire flow equation. For rigid-body fitting, we use a translational fast Fourier based scheme. We apply our segmentation, secondary structure elements identification, and rigid-body fitting techniques to the PSB 2011 cryo-EM modeling challenge data, and compare our results to those submitted from other research groups. The comparisons show that our software is capable of segmenting relatively accurate subunits from a viral or protein assembly, and that the high segmentation quality leads in turn to high-quality results of secondary structure elements identification and rigid-body fitting.

Zhang, Qin; Bettadapura, Radhakrishna

2012-01-01

94

Theory of the nucleation of protein macromolecular ions  

Microsoft Academic Search

Protein molecules are amphoteric and exist in aqueous solution as macromolecular ions that carry a charge which depends upon temperature and pH. Despite the repulsive Coulomb forces acting between them, protein macromolecular ions can form crystals in pH buffered solutions of strong electrolytes. It is proposed that the first step in the mechanism of crystallization is the formation of crystal

James K. Baird; Yeong Woo Kim

2002-01-01

95

Solution Structure of Proinsulin  

PubMed Central

The folding of proinsulin, the single-chain precursor of insulin, ensures native disulfide pairing in pancreatic ?-cells. Mutations that impair folding cause neonatal diabetes mellitus. Although the classical structure of insulin is well established, proinsulin is refractory to crystallization. Here, we employ heteronuclear NMR spectroscopy to characterize a monomeric analogue. Proinsulin contains a native-like insulin moiety (A- and B-domains); the tethered connecting (C) domain (as probed by {1H}-15N nuclear Overhauser enhancements) is progressively less ordered. Although the BC junction is flexible, residues near the CA junction exhibit ?-helical-like features. Relative to canonical ?-helices, however, segmental 13C?/? chemical shifts are attenuated, suggesting that this junction and contiguous A-chain residues are molten. We propose that flexibility at each C-domain junction facilitates prohormone processing. Studies of protease SPC3 (PC1/3) suggest that C-domain sequences contribute to cleavage site selection. The structure of proinsulin provides a foundation for studies of insulin biosynthesis and its impairment in monogenic forms of diabetes mellitus.

Yang, Yanwu; Hua, Qing-xin; Liu, Jin; Shimizu, Eri H.; Choquette, Meredith H.; Mackin, Robert B.; Weiss, Michael A.

2010-01-01

96

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

97

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.

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

2014-01-01

98

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.

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

2012-01-01

99

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

100

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

101

Use of Site-Specifically Tethered Chemical Nucleases to Study Macromolecular Reactions  

PubMed Central

During a complex macromolecular reaction multiple changes in molecular conformation and interactions with ligands may occur. X-ray crystallography may provide only a limited set of snapshots of these changes. Solution methods can augment such structural information to provide a more complete picture of a macromolecular reaction. We analyzed the changes in protein conformation and protein:nucleic acid interactions which occur during transcription initiation by using a chemical nuclease tethered to cysteines introduced site-specifically into the RNA polymerase of bacteriophage T7 (T7 RNAP). Changes in cleavage patterns as the polymerase steps through transcription reveal a series of structural transitions which mediate transcription initiation. Cleavage by tethered chemical nucleases is seen to be a powerful method for revealing the conformational dynamics of macromolecular reactions, and has certain advantages over cross-linking or energy transfer approaches.

Mukherjee, Srabani

2003-01-01

102

Testing of the structure of macromolecular polymer films containing solid active pharmaceutical ingredient (API) particles  

NASA Astrophysics Data System (ADS)

The aim of the present study was to investigate the structure of free films of Eudragit ® L 30D-55 containing different concentrations (0%, 1% or 5%) of diclofenac sodium by positron annihilation spectroscopy. The data revealed that the size of the free-volume holes and the lifetimes of ortho-positronium atoms decreased with increase of the API concentration. Films containing 5% of the API exhibited a different behavior during storage (17 °C, 65% relative humidity (RH)) in consequence of the uptake of water from the air.

Bölcskei, É.; Süvegh, K.; Marek, T.; Regdon, G.; Pintye-Hódi, K.

2011-07-01

103

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

104

Harvesting and Cryo-cooling Crystals of Membrane Proteins Grown in Lipidic Mesophases for Structure Determination by Macromolecular Crystallography  

PubMed Central

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 phases1-5, has gained considerable attention of late due to the successes it has had in the G protein-coupled receptor field6-21 (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 harvesting22,23. 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 rheologies4,26. 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.

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

2012-01-01

105

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

106

Visualizing macromolecular complexes with in situ liquid scanning transmission electron microscopy.  

PubMed

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. PMID:22386621

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

2012-11-01

107

Macromolecular structure and interaction studies of SigF and Usfx in Mycobacterium tuberculosis.  

PubMed

Abstract Mycobacterium tuberculosis (Mtb) is an intracellular human parasite that causes tuberculosis (TB). The parasite is capable of surviving under stress conditions. The gene expression in Mtb is regulated by sigma factor family of proteins. The SigF protein belongs to the sigma factor family, expressed during stationary and growth phase, 14 genes are directly regulated by SigF and has a role in the expression of the principal sigma factor SigB as well. The interacting partner Usfx, the anti SigF protein, controls the regulation of SigF. The structures of SigF and Usfx were evaluated using comparative modelling techniques and validated. The active sites of the two proteins were identified. The protein-protein interaction studies between SigF and Usfx reveal His53, Phe226 and Asp227 residues of SigF protein to be involved in binding with Arg108, Arg130 and Glu140 amino acids of Usfx. The present study focuses on identification of important residues involved in binding of SigF protein with Usfx, which are essential in the inhibition of transcription initiation and survival of Mtb. PMID:24405327

Mustyala, Kiran Kumar; Malkhed, Vasavi; Potlapally, Sarita Rajender; Chittireddy, Venkataramana Reddy; Vuruputuri, Uma

2014-06-01

108

Structural pathways for macromolecular and cellular transport across the blood-brain barrier during inflammatory conditions. Review.  

PubMed

This review presents an overview of the highlights of major concepts involving the anatomical routes for the transport of macromolecules and the transmigration of cellular elements across the blood-brain barrier (BBB) during inflammation. The particular focus will include inflammatory leukocytes, neoplastic cells and pathogenic microorganisms including specific types of viruses, bacteria and yeasts. The experimental animal models presented here have been employed successfully by the authors in several independent experiments during the past twenty-five years for investigations of pathologic alterations of the BBB after a variety of experimentally induced injuries and inflammatory conditions in mammalian and non-mammalian animal species. The initial descriptions of endothelial cell (EC) vesicles or caveolae serving as mini-transporters of fluid substances essentially served as a springboard for many subsequent discoveries during the past half century related to mechanisms of uptake of materials into ECs and whether or not pinocytosis is related to the transport of these materials across EC barriers under normal physiologic conditions and after tissue injury. In the mid-1970's, the authors of this review independently applied morphologic techniques (transmission electron microscopy-TEM), in conjunction with the plant protein tracer horseradish peroxidase (HRP) to investigate macromolecular transport structures that increased after the brain and spinal cord had been subjected to a variety of injuries. Based on morphologic evidence from these studies of BBB injury, the authors elaborated a unique EC system of modified caveolae that purportedly fused together forming transendothelial cell channels, and later similar EC profiles defined as vesiculo-canalicular or vesiculo-tubular structures (VTS, Lossinsky, et al., 1999). These EC structures were observed in association with increased BBB permeability of tracers including exogenously injected HRP, normally excluded from the intercellular milieu of the CNS. Subsequent studies of non-BBB-type tumor ECs determined that the EC VTS and other vesicular structures were defined by others as vesiculo-vacuolar organelles (VVOs, Kohn et al., 1992; Dvorak et al., 1996). Collectively, these structures appear to represent a type of anatomical gateway to the CNS likely serving as conduits. However, these CNS conduits become patent only in damaged ECs for the passage of macromolecules, and purportedly for inflammatory and neoplastic cells as well (Lossinsky et al., 1999). In this review, we focus attention on the similarities and differences between caveolae, fused racemic vesicular bundles, endothelial tubules and channels (VTS and the VVOs) that are manifest in normal, non-BBB-type blood vessels, and in the BBB after injury. This review will present evidence that the previous studies by the authors and other researchers established a framework for subsequent transmission (TEM), scanning (SEM) and high-voltage electron microscopic (HVEM) investigations concerning ultrastructural, ultracytochemical and immunoultra-structural alterations of the cerebral ECs and the mechanisms of the BBB transport that occurs after CNS injury. This review is not intended to include all of the many observations that might be included in a general historical overview of the development of the EC channel hypothesis, but it will discuss several of the major contributions. We have attempted to present some of the structural evidence that supports our early contributions and those made by other investigators by highlighting major features of these EC structures that are manifest in the injured BBB. We have focused on currently established concepts and principles related to mechanisms for the transendothelial transport of macromolecules after CNS injury and also offer a critical appraisal of some of this literature. Finally, we describe more recent concepts of transBBB avenues for viruses, including HIV-1, bacterial and mycotic organisms, as well as inflammatory and neoplastic cell adhesion and migration across the in

Lossinsky, A S; Shivers, R R

2004-04-01

109

A Model for Macromolecular Crystallization  

NASA Technical Reports Server (NTRS)

Macromolecular crystallization is a complex process. involving a system which typically has 5 or more components (macromolecule, water, buffer + counter ion, and precipitant). Whereas small molecules have only several well defined contacts in the crystal lattice, macromolecules generally have 10's or even 100's of contacts between molecules. These can range from hydrogen bonds (direct or water-mediated), through van der Waals, hydrophobic, salt bridges, and ion-mediated contacts. The latter interactions are stronger and require some specificity in the molecular alignment, while the others are weaker, more prevalent, and more promiscuous, i.e., can often be readily broken and reformed between other sites. Formation of a consistent, ordered, 3D structure may be impossible in the absence of any or presence of too many strong interactions. Further complicating the process is the inherent structural asymmetry of monomeric single chain macromolecules. The process of crystal nucleation and growth involves the ordered assembly of growth units into a defined 3D lattice. We suggest that for many macromolecules, particularly those that are monomeric, this involves a preliminary solution-phase assembly process into a growth unit having some symmetry prior to addition to the lattice, recapitulating the initial stages of the nucleation process. If this model is correct then fluids and crystal growth models assuming a strictly monodisperse nutrient solution need to be revised. Experimental evidence, based upon face growth rate, AFM, and fluorescence energy transfer data, for a postulated model of the nucleation of tetragonal lysozyme crystals and how it transitions into crystal growth will be presented.

Pusey, Marc L.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

110

Chemical structure and sources of the macromolecular, resistant, organic fraction isolated from a forest soil (Lacadée, south-west France)  

Microsoft Academic Search

The insoluble, non-hydrolyzable, macromolecular material isolated from a forest soil from Lacadée (south-west France) was examined via a combination of various methods: FTIR spectroscopy, elemental analysis, “off-line” pyrolysis and high resolution transmission electron microscopy. Such a resistant material, which accounts for ca. 25% of total humin, was shown to be chiefly composed of melanoidins and black carbon. Two types of

Natacha Poirier; Sylvie Derenne; Jean-Noël Rouzaud; Claude Largeau; André Mariotti; Jérôme Balesdent; Jocelyne Maquet

2000-01-01

111

The role of macromolecular stability in desiccation tolerance  

Microsoft Academic Search

The work presented in this thesis concerns a study on the molecular interactions that play a role in the macromolecular stability of desiccation-tolerant higher plant organs. Fourier transform infrared microspectroscopy was used as the main experimental technique to assess macromolecular structures within their native environment.Protein secondary structure and membrane phase behavior of Typha latifolia pollen were studied in the course

W. Wolkers

1998-01-01

112

Macromolecular Chemistry of Coalification. Quarterly Report, August 1, 1984-October 31, 1984.  

National Technical Information Service (NTIS)

The objective is to examine the changes in macromolecular structure which occur during coalification. Observance of these macromolecular changes will be used to provide insight into the complex coalification process. Scope of work includes the following: ...

J. W. Larsen J. Kovac S. E. Shawver

1984-01-01

113

Crystal structure of Jararacussin-I: The highly negatively charged catalytic interface contributes to macromolecular selectivity in snake venom thrombin-like enzymes  

PubMed Central

Snake venom serine proteinases (SVSPs) are hemostatically active toxins that perturb the maintenance and regulation of both the blood coagulation cascade and fibrinolytic feedback system at specific points, and hence, are widely used as tools in pharmacological and clinical diagnosis. The crystal structure of a thrombin-like enzyme (TLE) from Bothrops jararacussu venom (Jararacussin-I) was determined at 2.48 Å resolution. This is the first crystal structure of a TLE and allows structural comparisons with both the Agkistrodon contortrix contortrix Protein C Activator and the Trimeresurus stejnegeri plasminogen activator. Despite the highly conserved overall fold, significant differences in the amino acid compositions and three-dimensional conformations of the loops surrounding the active site significantly alter the molecular topography and charge distribution profile of the catalytic interface. In contrast to other SVSPs, the catalytic interface of Jararacussin-I is highly negatively charged, which contributes to its unique macromolecular selectivity.

Ullah, A; Souza, T A C B; Zanphorlin, L M; Mariutti, R B; Santana, V S; Murakami, M T; Arni, R K

2013-01-01

114

La structure des solutions aqueuses  

NASA Astrophysics Data System (ADS)

En commençant par l'étude par diffraction neutronique de la structure des liquides moléculaires puis de l'hydratation des ions en solution, ce cours montrera comment les principes présentés lors des cours précédents peuvent être appliqués à des systèmes aqueux. Des exemples tirés de la littérature seront utilisés pour illustrer les considérations expérimentales propre à ce domaine et le genre d'informations que nous pouvons obtenir. Ce cours montrera également l'applicaton de la diffraction neutronique à des systèmes d'intérêt biologique et environnemental et se terminera par un examen de la complémentarité fournie par la diffraction des rayons X, l'EXAFS et la RMN.

Powell, D. H.

2003-09-01

115

Experimental Structural Studies of Solutes in Aqueous Solution  

SciTech Connect

The principles of experimental methods to study the structure and the hydrogen bonding of hydrated solutes in aqueous solution are presented, and whether theoretical simulations can produce comparable information as the experimental ones is discussed. Two structure methods, extended X-ray absorption fine structure (EXAFS) and large angle X-ray scattering (LAXS), and one method to study the hydrogen bonding in hydrated species in aqueous solution, double difference infrared spectroscopy of HDO, are presented.

Persson, Ingmar [Department of Chemistry, Swedish University of Agricultural Sciences, P.O. Box 7015, SE-750 07 Uppsala (Sweden)

2007-11-29

116

Method for Preparing Macromolecular Polyoxymethylene.  

National Technical Information Service (NTIS)

The present invention is concerned with the methods for preparing macromolecular polyoxymethylene (polyformaldehyde) from crystalline trioxane. A method for preparing macromolecular polyoxymethylene from polycrystalline trioxane by means of shock compress...

L. V. Barbare F. I. Dubovitsky A. N. Dremin

1979-01-01

117

Macromolecular Characterization of Poly(bis(M-Chlorophenoxy)-Phosphazene).  

National Technical Information Service (NTIS)

The macromolecular structures and structure-property relationships of five poly(bis(m-chlorophenoxy)phosphazene) samples are critically analyzed. The polymers are found to have high molecular weights and broad, bimodal molecular weight distributions. Diff...

G. L. Hagnauer B. R. LaLiberte R. E. Singler S. J. Kalian E. R. Plumer

1976-01-01

118

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

119

Gas-phase processes and measurements of macromolecular properties in solution: On the possibility of false positive and false negative signals of protein unfolding  

Microsoft Academic Search

Electrospray ionization mass spectrometry is increasingly applied to study protein behavior in solution, including characterization of their higher order structure, conformational dynamics and interactions with small ligands and other biopolymers. However, actual measurements of fundamental ionic parameters (mass and charge) take place in vacuum, and an array of gas phase processes occurring prior to protein ion detection and characterization may

Rinat R. Abzalimov; Agya K. Frimpong; Igor A. Kaltashov

2006-01-01

120

Macromolecular crowding and its potential impact on nuclear function.  

PubMed

It is well established, that biochemical reactions are dependent on pH, ionic strength, temperature and the concentration of reactants. However, the steric repulsion among bulky components of biological systems also affect biochemical behavior: The 'excluded volume effect of macromolecular crowding' drives bulky components into structurally compact organizations, increases their thermodynamic activities and slows down diffusion. The very special composition of the cell nucleus, which is packed with high-molecular chromatin, ribonucleo-particles and associated proteins, suggests that crowding-effects are part of nuclear functionality. Realizing that many nuclear processes, notably gene transcription, hnRNA splicing and DNA replication, use macromolecular machines, and taking into account that macromolecular crowding provides a cooperative momentum for the assembly of macromolecular complexes, we here elaborate why macromolecular crowding may be functionally important in supporting the statistical significance of nuclear activities. PMID:18723053

Richter, Karsten; Nessling, Michelle; Lichter, Peter

2008-11-01

121

Plasma-Assisted Biological Macromolecular Crystallization  

NASA Astrophysics Data System (ADS)

Improvement in the crystallization probability of biological macromolecules by plasma irradiation is demonstrated with lysozymes from hen egg whites. This novel technique of ``plasma-assisted biological macromolecular crystallization'' is readily carried out with a relatively simple apparatus, and is likely to become a powerful tool in discerning the three-dimensional structure of such macromolecules.

Ito, Tsuyohito; Ito, Takuhiro; Yokoyama, Shigeyuki

2011-02-01

122

NMR Studies of Aqueous Solution Structure.  

National Technical Information Service (NTIS)

Aqueous solutions of urea and related compounds exhibit anomalous thermodynamic and transport properties which have been extensively studied, and rationalized by arguments based on the loosely defined concept of solution structure. Aspects of molecular or...

R. L. Vold

1972-01-01

123

Structure of solutions of nonelectrolytes  

Microsoft Academic Search

Using the technique of spin echo NMR, concentration dependences of the coefficient of self-diffusion D in aqueous solutions of acetone in the presence of additions of electrolytes were obtained. For solutions in the presence of KC1, NaC1, and A1C1 a, the temperature dependences of D were also obtained, and the activation energy calculated. These data are evidence of the existence

A. I. Toryanik; I. V. Matyash; V. V. Kisel'nik

1968-01-01

124

Macromolecular Crystallization in Microfluidics for the International Space Station  

NASA Technical Reports Server (NTRS)

At NASA's Marshall Space Flight Center, the Iterative Biological Crystallization (IBC) project has begun development on scientific hardware for macromolecular crystallization on the International Space Station (ISS). Currently ISS crystallization research is limited to solution recipes that were prepared on the ground prior to launch. The proposed hardware will conduct solution mixing and dispensing on board the ISS, be fully automated, and have imaging functions via remote commanding from the ground. Utilizing microfluidic technology, IBC will allow for on orbit iterations. The microfluidics LabChip(R) devices that have been developed, along with Caliper Technologies, will greatly benefit researchers by allowing for precise fluid handling of nano/pico liter sized volumes. IBC will maximize the amount of science return by utilizing the microfluidic approach and be a valuable tool to structural biologists investigating medically relevant projects.

Monaco, Lisa A.; Spearing, Scott

2003-01-01

125

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

126

Chitosan structure in aqueous solution  

Microsoft Academic Search

Chitosans having three different degrees of acetylation ( DA) were studied in acid solution using the uranyl staining technique and electron microscopy. Strings of approximately spherical aggregates were seen. The aggregates were interpreted as micelle-like agglomerates formed by almost fully acetylated polysaccharide, interconnected by blocks of almost fully deacetylated polysaccharide stretched by electrostatic repulsion. These agglomerates include NH 3 +

V. I. Pedroni; P. C. Schulz; M. E. Gschaider; N. Andreucetti

2003-01-01

127

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

128

Macromolecular structure analysis and effective liquefaction pretreatment. Quarterly technical progress report, 1 April 1991--30 June 1991.  

National Technical Information Service (NTIS)

Differential scanning calorimetry (DSC) and solvent swelling were used to evaluate structural changes at low temperatures (<350 C) before any major pyrolytic bond breakage occurs. Results reveal existence of reversible structural changes together with an ...

E. M. Suuberg Y. Yun W. D. Lilly

1991-01-01

129

Microgravity and Macromolecular Crystallography  

NASA Technical Reports Server (NTRS)

Macromolecular crystal growth has been seen as an ideal experiment to make use of the reduced acceleration environment provided by an orbiting spacecraft. The experiments are small, simply operated and have a high potential scientific and economic impact. In this review we examine the theoretical reasons why microgravity should be a beneficial environment for crystal growth and survey the history of experiments on the Space Shuttle Orbiter, on unmanned spacecraft, and on the Mir space station. Finally we outline the direction for optimizing the future use of orbiting platforms.

Kundrot, Craig E.; Judge, Russell A.; Pusey, Marc L.; Snell, Edward H.; Rose, M. Franklin (Technical Monitor)

2000-01-01

130

Global molecular structure and interfaces : refining an RNA : RNA complex structure using solution x-ray scattering data.  

SciTech Connect

Determining the global architecture of multicomponent systems is a central problem in understanding biomacromolecular machines. Defining interfaces among components and the global structure of multicomponent systems is a central problem in understanding the biological interactions on a molecular level. We demonstrate that solution X-ray scattering data can be used to precisely determine intermolecular interfaces from just the subunit structures, in the complete absence of intermolecular NMR restraints using an example of a 30 kDa RNA-RNA complex. The backbone root-mean-square deviation (rmsd) between structures that are determined using the scattering data and using intermolecular distance restraints is about 0.4 {angstrom}. Further, we refined the global structure of the complex using scattering data as a global restraint. The rmsd in backbone structures that are determined with and without the scattering data refinement is about 3.2 {angstrom}, suggesting the impact of the refinement to the overall structure. Information about the 'global correctness' of solution RNA structures could not be practically obtained otherwise, due to the molecular nature of the RNA molecules, but could only be defined by the scattering data together by residual dipolar couplings. This method provides a powerful new approach for refining global structures of macromolecular complexes whose subunits are elongated.

Zuo, X.; Wang, J.; Foster, T. R.; Schwieters, C. D.; Tiede, D. M.; Butcher, S. E.; Wang, Y.-X.; Chemical Sciences and Engineering Division; NCI-Frederick; Univ. of Wisconin at Madison; NIH

2008-03-19

131

Mechanisms, kinetics, impurities and defects: consequences in macromolecular crystallization.  

PubMed

The nucleation and growth of protein, nucleic acid and virus crystals from solution are functions of underlying kinetic and thermodynamic parameters that govern the process, and these are all supersaturation-dependent. While the mechanisms of macromolecular crystal growth are essentially the same as for conventional crystals, the underlying parameters are vastly different, in some cases orders of magnitude lower, and this produces very different crystallization processes. Numerous physical features of macromolecular crystals are of serious interest to X-ray diffractionists; the resolution limit and mosaicity, for example, reflect the degree of molecular and lattice order. The defect structure of crystals has an impact on their response to flash-cooling, and terminal crystal size is dependent on impurity absorption and incorporation. The variety and extent of these issues are further unique to crystals of biological macromolecules. All of these features are amenable to study using atomic force microscopy, which provides direct images at the nanoscale level. Some of those images are presented here. PMID:24699728

McPherson, Alexander; Kuznetsov, Yurii G

2014-04-01

132

Refined solution structure of human profilin I.  

PubMed Central

Profilin is a ubiquitous eukaryotic protein that binds to both cytosolic actin and the phospholipid phosphatidylinositol-4,5-bisphosphate. These dual competitive binding capabilities of profilin suggest that profilin serves as a link between the phosphatidyl inositol cycle and actin polymerization, and thus profilin may be an essential component in the signaling pathway leading to cytoskeletal rearrangement. The refined three-dimensional solution structure of human profilin I has been determined using multidimensional heteronuclear NMR spectroscopy. Twenty structures were selected to represent the solution conformational ensemble. This ensemble of structures has root-mean-square distance deviations from the mean structure of 0.58 A for the backbone atoms and 0.98 A for all non-hydrogen atoms. Comparison of the solution structure of human profilin to the crystal structure of bovine profilin reveals that, although profilin adopts essentially identical conformations in both states, the solution structure is more compact than the crystal structure. Interestingly, the regions that show the most structural diversity are located at or near the actin-binding site of profilin. We suggest that structural differences are reflective of dynamical properties of profilin that facilitate favorable interactions with actin. The global folding pattern of human profilin also closely resembles that of Acanthamoeba profilin I, reflective of the 22% sequence identity and approximately 45% sequence similarity between these two proteins.

Metzler, W. J.; Farmer, B. T.; Constantine, K. L.; Friedrichs, M. S.; Lavoie, T.; Mueller, L.

1995-01-01

133

On completeness of RFM solution structures  

NASA Astrophysics Data System (ADS)

The R-Function Method (RFM) solution structure is a functional expression that satisfies all given boundary conditions exactly and contains some undetermined functional components. It is complete if there exists a choice of undetermined component that transform the solution structure into an exact solution. Such a structure was used by Kantorovich (Kantorovich and Krylov, 1958) and his students to solve boundary value problems with homogeneous boundary conditions on geometrically simple domains. RFM is based on the theory of R-functions (Rvachev, 1982) that allows construction of a set of functions vanishing on the boundary and can be applied to problems with arbitrarily complex domains and boundary conditions. The resulting solution method is essentially meshfree, in the sense that the spatial discretization no longer needs to conform to the geometry of the domain, and can be completely automated. This paper summarizes the main principles of RFM, proves its completeness, and presents numerical results for several simple test problems.

Rvachev, V. L.; Sheiko, T. I.; Shapiro, V.; Tsukanov, I.

134

Macromolecular crystal growing system  

NASA Technical Reports Server (NTRS)

A macromolecular crystal growing system especially designed for growing crystals in the low gravity of space as well as the gravity of earth includes at least one tray assembly, a carrier assembly which receives the tray, and a refrigeration-incubation module in which the carrier assembly is received. The tray assembly includes a plurality of sealed chambers with a plastic syringe and a plug means for the double tip of the syringe provided therein. Ganging mechanisms operate the syringes and plugs simultaneously in a precise and smooth operation. Preferably, the tray assemblies are mounted on ball bearing slides for smooth operation in inserting and removing the tray assemblies into the carrier assembly. The plugging mechanism also includes a loading control mechanism. A mechanism for leaving a syringe unplugged is also provided.

Snyder, Robert S. (inventor); Herren, Blair J. (inventor); Carter, Daniel C. (inventor); Yost, Vaughn H. (inventor); Bugg, Charles E. (inventor); Delucas, Lawrence J. (inventor); Suddath, Fred L. (inventor)

1991-01-01

135

The vibron dressing in ?-helicoidal macromolecular chains  

NASA Astrophysics Data System (ADS)

We present a study of the physical properties of the vibrational excitation in ?-helicoidal macromolecular chains, caused by the interaction with acoustical and optical phonon modes. The influence of the temperature and the basic system parameters on the vibron dressing have been analyzed by employing the simple mean-field approach based on the variational extension of the Lang—Firsov unitary transformation. The applied approach predicts a region in system parameter space where one has an abrupt transition from a partially dressed (light and mobile) to a fully dressed (immobile) vibron state. We found that the boundary of this region depends on system temperature and the type of bond among structural elements in the macromolecular chain.

?evizovi?, D.; Galovi?, S.; Reshetnyak, A.; Ivi?, Z.

2013-06-01

136

Statistics of multiscale fluctuations in macromolecular systems.  

PubMed

An approach is suggested for treating multiscale fluctuations in macromolecular systems. The emphasis is on the statistical properties of such fluctuations. The approach is illustrated by a macromolecular system with mesoscopic fluctuations between the states of atomic orbitals. Strong-orbital and weak-orbital couplings fluctuationally arise, being multiscale in space and time. Statistical properties of the system are obtained by averaging over the multiscale fluctuations. The existence of such multiscale fluctuations causes phase transitions between strong-coupling and weak-coupling states. These transitions are connected with structure and size transformations of macromolecules. An approach for treating density and size multiscale fluctuations by means of classical statistical mechanics is also advanced. PMID:22594677

Yukalov, Vyacheslav I; Yukalova, Elizaveta P

2012-07-26

137

The Structure of Cyclooctatetraeneiron Tricarbonyl in Solution.  

National Technical Information Service (NTIS)

It was recently reported (in AD-638 945) that cyclooctatetraeniron tricarbonyl (COTFe(CO)3) in solution has a 1,3-diene-bonded structure (I) and that the nmr spectrum of the compound at -145C is that of the 'frozen' structure I. Two other groups of worker...

F. A. L. Anet H. D. Kaesz A. Maasbol S. Winstein

1967-01-01

138

RapiData: a Practical Course in Macromolecular X-ray Diffraction Data Measurement and Structure Solving at the NSLS  

SciTech Connect

RapiData provides two days of high-level lectures, then two more of experimental work on several beamlines of the National Synchrotron Light Source, for about 50 students. Students are invited to bring their own research projects for measurement, and about half of them do. The students frequently solve half a dozen structures during the course. Tutorials by the lecturers run throughout the data-collection period. The crystal-preparation laboratory is popular for tutorials and practice, and often there is a beamline available for practice. This article provides details about the organization of the course and tells some of the reasons for its success.

Sweet, R.; Soares, A

2010-01-01

139

A crystallographic station for structural investigations of macromolecular crystals on the synchrotron beam of the VEPP-3 storage ring  

NASA Astrophysics Data System (ADS)

A station designed to speed up the collection of integral intensity data from protein and virus crystals is constructed on the synchrotron radiation beam of the VEPP-3 storage ring. A flat triangular Si crystal cut at 8° relative to the (111) plane is used to monochromatize the radiation. A conventional Arndt-Wonacott rotation camera is used to collect structural information. The station also includes an optical bench which can turn about the axis coinciding with that of the monochromator, and a set of slits to cut the background and to form the beam. The ionization chamber serves to adjust the monochromator and to monitor the beam. Numerical results of first measurements from protein crystals as well as plans for future work are presented.

Popov, A. N.; Antson, A. A.; Belyaev, V. V.; Bondarenko, K. P.; Harutyunyan, E. H.; Kheiker, D. M.; Sheromov, M. A.; Mytnychenko, S. V.

1989-10-01

140

Water structure in concentrated lithium chloride solutions  

Microsoft Academic Search

The radial pair distribution functions gHH(r) and gOH(r) (to a good approximation) of 1 and 10 m solutions of lithium chloride in water have been obtained from neutron diffraction. It turns out that the intermolecular water structure in a solution of 10 m is affected considerably by the presence of ions—the number of hydrogen bonds is about 70% lower than

R. H. Tromp; G. W. Neilson; A. K. Soper

1992-01-01

141

Atomic-resolution structural information from scattering experiments on macromolecules in solution.  

PubMed

The pair-distance distribution function (PDDF) contains all structural information probed in an elastic scattering experiment of macromolecular solutions. However, in small-angle x-ray scattering (SAXS) or small-angle neutron scattering (SANS) experiments only their Fourier transform is measured over a restricted range of scattering angles. We therefore developed a mathematically simple and computationally efficient method to calculate the PDDFs as well as accurate scattering intensities from molecular dynamics simulations. The calculated solution scattering intensities are in excellent agreement with SAXS and wide-angle x-ray scattering (WAXS) experiments for a series of proteins. The corresponding PDDFs are remarkably rich in features reporting on the detailed protein structure. Using an inverse Fourier transform method, most of these features can be recovered if scattering intensities are measured up to a momentum transfer of q?2-3Å(-1). Our results establish that high-precision solution scattering experiments utilizing x-ray free-electron lasers and third generation synchrotron sources can resolve subnanometer structural detail, well beyond size, shape, and fold. PMID:23767571

Köfinger, Jürgen; Hummer, Gerhard

2013-05-01

142

Atomic-resolution structural information from scattering experiments on macromolecules in solution  

NASA Astrophysics Data System (ADS)

The pair-distance distribution function (PDDF) contains all structural information probed in an elastic scattering experiment of macromolecular solutions. However, in small-angle x-ray scattering (SAXS) or small-angle neutron scattering (SANS) experiments only their Fourier transform is measured over a restricted range of scattering angles. We therefore developed a mathematically simple and computationally efficient method to calculate the PDDFs as well as accurate scattering intensities from molecular dynamics simulations. The calculated solution scattering intensities are in excellent agreement with SAXS and wide-angle x-ray scattering (WAXS) experiments for a series of proteins. The corresponding PDDFs are remarkably rich in features reporting on the detailed protein structure. Using an inverse Fourier transform method, most of these features can be recovered if scattering intensities are measured up to a momentum transfer of q?2-3Å-1. Our results establish that high-precision solution scattering experiments utilizing x-ray free-electron lasers and third generation synchrotron sources can resolve subnanometer structural detail, well beyond size, shape, and fold.

Köfinger, Jürgen; Hummer, Gerhard

2013-05-01

143

Structure of aqueous potassium metaborate solution  

NASA Astrophysics Data System (ADS)

The structure of aqueous potassium metaborate solutions has been confirmed by X-ray scattering, Raman spectra and species distribution calculation. The optimized structure of B(OH)4- was obtained by density functional theory calculation. The hydration distance and hydration number of K+ in aqueous potassium metaborate solution were given by X-ray scattering. The B-O(H2O) distance in hydrated anion B(OH)4- were determined to be 0.37 nm with the hydration number of 2.3 per hydroxyl(-OH). The K-B distance of the contact ions KB(OH)40 was measured to be 0.34 nm.

Zhu, F. Y.; Fang, C. H.; Fang, Y.; Zhou, Y. Q.; Ge, H. W.; Liu, H. Y.

2014-07-01

144

Assembly of allosteric macromolecular switches: lessons from PKA  

PubMed Central

Protein kinases are dynamic molecular switches that have evolved to be only transiently activated. Kinase activity is embedded within a conserved kinase core, which is typically regulated by associated domains, linkers and interacting proteins. Moreover, protein kinases are often tethered to large macromolecular complexes to provide tighter spatiotemporal control. Thus, structural characterization of kinase domains alone is insufficient to explain protein kinase function and regulation in vivo. Recent progress in structural characterization of cyclic AMP-dependent protein kinase (PKA) exemplifies how our knowledge of kinase signalling has evolved by shifting the focus of structural studies from single kinase subunits to macromolecular complexes.

Taylor, Susan S.; Ilouz, Ronit; Zhang, Ping; Kornev, Alexandr P.

2014-01-01

145

Molecular structure of aqueous solutions of hexamethylenetetramine  

Microsoft Academic Search

Hexamethylenetetramine (HMT) (CH2)6N 4 is one of the first compounds in which the structure was determined by x-ray diffraction. The HMT molecule is like a fragment of the diamond structure in which part of the CH~ group is replaced by nitrogen atoms [1]. An aqueous solution of HMT is a system in which extremely complicated interactions take place between the

G. G. Malenkov; A. I. Toryanik

1976-01-01

146

Solution procedures for nonlinear structural dynamic analysis  

Microsoft Academic Search

A review of the solution techniques most widely used in nonlinear structural dynamics is presented. For nonlinear transient responses several explicit and implicit direct integration methods are compared with respect to accuracy, stability and computational efficiency. It is concluded that the choice of a suitable method depends upon the nature of the method, the formulation of finite element models, and

1980-01-01

147

Solution structure of RNase P RNA  

PubMed Central

The ribonucleoprotein enzyme ribonuclease P (RNase P) processes tRNAs by cleavage of precursor-tRNAs. RNase P is a ribozyme: The RNA component catalyzes tRNA maturation in vitro without proteins. Remarkable features of RNase P include multiple turnovers in vivo and ability to process diverse substrates. Structures of the bacterial RNase P, including full-length RNAs and a ternary complex with substrate, have been determined by X-ray crystallography. However, crystal structures of free RNA are significantly different from the ternary complex, and the solution structure of the RNA is unknown. Here, we report solution structures of three phylogenetically distinct bacterial RNase P RNAs from Escherichia coli, Agrobacterium tumefaciens, and Bacillus stearothermophilus, determined using small angle X-ray scattering (SAXS) and selective 2?-hydroxyl acylation analyzed by primer extension (SHAPE) analysis. A combination of homology modeling, normal mode analysis, and molecular dynamics was used to refine the structural models against the empirical data of these RNAs in solution under the high ionic strength required for catalytic activity.

Kazantsev, Alexei V.; Rambo, Robert P.; Karimpour, Sina; SantaLucia, John; Tainer, John A.; Pace, Norman R.

2011-01-01

148

Structural studies of polyurethane ionomer solutions  

NASA Astrophysics Data System (ADS)

Except for a number of conductivity and viscometric measurements, structural studies of polyurethane ionomer solutions are lacking in literature. Polyurethane ionomers in polar solvents are shown to exhibit polyelectrolyte behavior. So these ionomer solutions also form model systems to investigate the characteristic behavior of salt free polyelectrolyte solutions. In this study, viscometry and light scattering experiments have been performed on model polyurethane ionomers, which have regularly positioned ionic groups. The model system is synthesized as a 1:1 copolymer of polytetramethylene oxide (PTMO) and 4-4'-diphenyl methane diisocyanate (MDI) which is subsequently ionized by abstraction with sodium hydride (NaH) and derivatization with 1,3 propane sultone. The separation distance between the ionic groups is varied by varying the molecular weight of PTMO. Viscometric measurements of these ionomers in a polar solvent, N,N-dimethyl acetamide (DMAc), have verified that they exhibit polyelectrolyte behavior. Static and Dynamic Light Scattering have been applied to these ionomer solutions to reveal important information about the structures in solution. The results of the analysis of the light scattering data will be presented.

Nomula, Srinivas; Cooper, Stuart

1996-03-01

149

A database of macromolecular motions.  

PubMed Central

We describe a database of macromolecular motions meant to be of general use to the structural community. The database, which is accessible on the World Wide Web with an entry point at http://bioinfo.mbb.yale.edu/MolMovDB , attempts to systematize all instances of protein and nucleic acid movement for which there is at least some structural information. At present it contains >120 motions, most of which are of proteins. Protein motions are further classified hierarchically into a limited number of categories, first on the basis of size (distinguishing between fragment, domain and subunit motions) and then on the basis of packing. Our packing classification divides motions into various categories (shear, hinge, other) depending on whether or not they involve sliding over a continuously maintained and tightly packed interface. In addition, the database provides some indication about the evidence behind each motion (i.e. the type of experimental information or whether the motion is inferred based on structural similarity) and attempts to describe many aspects of a motion in terms of a standardized nomenclature (e.g. the maximum rotation, the residue selection of a fixed core, etc.). Currently, we use a standard relational design to implement the database. However, the complexity and heterogeneity of the information kept in the database makes it an ideal application for an object-relational approach, and we are moving it in this direction. Specifically, in terms of storing complex information, the database contains plausible representations for motion pathways, derived from restrained 3D interpolation between known endpoint conformations. These pathways can be viewed in a variety of movie formats, and the database is associated with a server that can automatically generate these movies from submitted coordinates.

Gerstein, M; Krebs, W

1998-01-01

150

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

151

Viscosity and structure of Ormosil solutions  

Microsoft Academic Search

PDMS (polydimethylsiloxane)\\/TEOS (tetraethoxysilane) system Ormosils (organically modified silicates) can be rubbery or rigid, depending on their chemical composition and processing conditions. In order to determine the relationship between the viscosity and the structure of the Ormosil solutions through the sol-to-gel transition, five kinds of sols (three levels of PDMS, three levels of H2O) were prepared with refluxing. Viscosities were measured

Yasukazu Hoshino; John D. Mackenzie

1995-01-01

152

Universal BPS structure of stationary supergravity solutions  

NASA Astrophysics Data System (ADS)

We study asymptotically flat stationary solutions of four-dimensional supergravity theories via the associated fraktur G/fraktur H* pseudo-Riemannian non-linear sigma models in three spatial dimensions. The Noether charge Script C associated to fraktur G is shown to satisfy a characteristic equation that determines it as a function of the four-dimensional conserved charges. The matrix Script C is nilpotent for non-rotating extremal solutions. The nilpotency degree of Script C is directly related to the BPS degree of the corresponding solution when they are BPS. Equivalently, the charges can be described in terms of a Weyl spinor |Script Crangle of Spin*(2Script N), and then the characteristic equation becomes equivalent to a generalisation of the Cartan pure spinor constraint on |Script Crangle. The invariance of a given solution with respect to supersymmetry is determined by an algebraic `Dirac equation' on the Weyl spinor |Script Crangle. We explicitly solve this equation for all pure supergravity theories and we characterise the stratified structure of the moduli space of asymptotically Taub-NUT black holes with respect to their BPS degree. The analysis is valid for any asymptotically flat stationary solutions for which the singularities are protected by horizons. The fraktur H*-orbits of extremal solutions are identified as Lagrangian submanifolds of nilpotent orbits of fraktur G, and so the moduli space of extremal spherically symmetric black holes is identified as a Lagrangian subvariety of the variety of nilpotent elements of fraktur g. We also generalise the notion of active duality transformations to an `almost action' of the three-dimensional duality group fraktur G on asymptotically flat stationary solutions.

Bossard, Guillaume; Nicolai, Hermann; Stelle, K. S.

2009-07-01

153

Enhancement and simplification of macromolecular images.  

PubMed Central

Computer graphics programs have been devised to display selected atomic features and to simplify images of complex macromolecular structures. By using boundary outlines, adjustment of size and shape of the molecular components, color coding, shading, and selective omission of obscuring detail, attention can be focused on specific interactions which determine higher levels of organization. A balanced color table has been constructed in which different hues have equal steps in brightness; this table has facilitated distinction of atom types and sequence coding together with representation of an optimum range of depth cueing and surface shading. The graphics system has been used with the atomic coordinates of the tobacco mosaic virus structure to simplify images of the protein subunit, to illustrate intermolecular interactions, and to relate subunit packing arrangements in different assemblies to the underlying atomic structure. The system has also been used to construct a schematic representation of the polyomavirus capsid, based on low resolution data. Application of artistic methods contributes to the effective presentation and interpretation of detailed scientific information about complex macromolecular structures. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18

Namba, K; Caspar, D L; Stubbs, G

1988-01-01

154

Organic sulfur in macromolecular sedimentary organic matter. I. Structure and origin of sulfur-containing moieties in kerogen, asphaltenes and coal as revealed by flash pyrolysis  

SciTech Connect

The distributions of sulfur-containing compounds generated by flash pyrolysis of macromolecular sedimentary organic matter (kerogen, coal, asphaltenes) were studied by gas chromatography in combination with S-selective flame photometric detection or mass spectrometry. The abundance of S-containing pyrolysis products in the pyrolysates relative to other products was highly variable depending on the sample but the types of products were generally similar, being mainly composed of gaseous compounds and low molecular weight alkylthiophenes and alkylbenzothiophenes. The distribution patterns of the alkylated thiophenes were dominated by a limited number of all theoretically possible isomers. The alkyl substitution patterns of the dominant isomers bear a strong similarity to those of the organic S compounds present in the GC-amenable fractions of bitumens and immature oils. Therefore, it is suggested that these S-containing pyrolysis products are formed by pyrolysis of related thiophenic and benzothiophenic moieties present in the macromolecular sedimentary substances. Specific examples include those with linear alkyl, iso and anteiso alkyl, isoprenoid alkyl and steroidal carbon skeletons. The presence of higher molecular weight alkylthiophenes and alkylbenzothiophenes with these same carbon skeletons in pyrolysates of S-rich kerogens provided further evidence for the presence of these S-containing moieties. It is likely that these moieties have been formed by abiogenic S incorporation into sedimentary organic matter during early diagenesis.

Damste, J.S.S.; Eglinton, T.I.; De Leeuw, J.W.; Schenck, P.A. (Delft Univ. of Technology (Netherlands))

1989-04-01

155

Organic sulphur in macromolecular sedimentary organic matter: I. Structure and origin of sulphur-containing moieties in kerogen, asphaltenes and coal as revealed by flash pyrolysis  

NASA Astrophysics Data System (ADS)

The distributions of sulphur-containing compounds generated by flash pyrolysis of macromolecular sedimentary organic matter (kerogen, coal, asphaltenes) were studied by gas chromatography in combination with Sselective flame photometric detection or mass spectrometry. The abundance of S-containing pyrolysis products in the pyrolysates relative to other products was highly variable depending on the sample but the types of products were generally similar, being mainly composed of "gaseous" compounds ( e.g., hydrogen sulphide) and low molecular weight alkylthiophenes and alkylbenzothiophenes. The distribution patterns of the alkylated thiophenes were dominated by a limited number of all theoretically possible isomers. The alkyl substitution patterns of the dominant isomers bear a strong similarity to those of the organic S compounds present in the GC-amenable fractions of bitumens and immature oils. Therefore, it is suggested that these S-containing pyrolysis products are formed by pyrolysis of related thiophenic and benzothiophenic moieties present in the macromolecular sedimentary substances. Specific examples include those with linear alkyl, iso and anteiso alkyl, isoprenoid alkyl and steroidal carbon skeletons. The presence of higher molecular weight alkylthiophenes and alkylbenzothiophenes with these same carbon skeletons in pyrolysates of S-rich kerogens provided further evidence for the presence of these S-containing moieties. It is likely that these moieties have been formed by abiogenic S incorporation into sedimentary organic matter during early diagenesis.

Sinninghe Damsté, Jaap S.; Eglinton, Timothy I.; De Leeuw, Jan W.; Schenck, P. A.

1989-04-01

156

Amplifying the macromolecular crowding effect using nanoparticles.  

PubMed

The melting temperature (T(m)) of DNA is affected not only by salt but also by the presence of high molecular weight (MW) solutes, such as polyethylene glycol (PEG), acting as a crowding agent. For short DNAs in a solution of low MW PEGs, however, the change of excluded volume upon melting is very small, leading to no increase in T(m). We demonstrate herein that by attaching 12-mer DNAs to gold nanoparticles, the excluded volume change was significantly increased upon melting, leading to increased T(m) even with PEG 200. Larger AuNPs, higher MW PEGs, and higher PEG concentrations show even larger effects in stabilizing the DNA. This study reveals a unique and fundamental feature at nanoscale due to geometric effects. It also suggests that weak interactions can be stabilized by a combination of polyvalent binding and the enhanced macromolecular crowding effect using nanoparticles. PMID:22175804

Zaki, Ahmed; Dave, Neeshma; Liu, Juewen

2012-01-11

157

Structures of TraI in solution.  

PubMed

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

2014-06-01

158

Macromolecular assembly of polycystin-2 intracytosolic C-terminal domain  

PubMed Central

Mutations in PKD2 are responsible for approximately 15% of the autosomal dominant polycystic kidney disease cases. This gene encodes polycystin-2, a calcium-permeable cation channel whose C-terminal intracytosolic tail (PC2t) plays an important role in its interaction with a number of different proteins. In the present study, we have comprehensively evaluated the macromolecular assembly of PC2t homooligomer using a series of biophysical and biochemical analyses. Our studies, based on a new delimitation of PC2t, have revealed that it is capable of assembling as a homotetramer independently of any other portion of the molecule. Our data support this tetrameric arrangement in the presence and absence of calcium. Molecular dynamics simulations performed with a modified all-atoms structure-based model supported the PC2t tetrameric assembly, as well as how different populations are disposed in solution. The simulations demonstrated, indeed, that the best-scored structures are the ones compatible with a fourfold oligomeric state. These findings clarify the structural properties of PC2t domain and strongly support a homotetramer assembly of PC2.

Ferreira, Frederico M.; Oliveira, Leandro C.; Germino, Gregory G.; Onuchic, Jose N.; Onuchic, Luiz F.

2011-01-01

159

Structure and interactions in simple solutions.  

PubMed Central

Neutron scattering with hydrogen/deuterium isotopic substitution techniques has been used to investigate the full range of structural interactions in a dilute 0.02 mol fraction solution of tertiary butanol in water, both in the absence and in the presence of a small amount of sodium chloride. Emphasis is given to the detailed pictures of the intermolecular interactions that have been derived using the empirical potential structure refinement technique. Analysis has been performed to the level of the spatial density distribution functions that illustrate the orientational dependence of the intermolecular interactions between all combinations of molecular and ionic components. The results show the key structural motifs involved in the interactions between the various components in a complex aqueous system. They underline the structural versatility of the water molecule in accommodating a range of different kinds of interactions while retaining its characteristic first-neighbour interaction geometry. Within this framework, the results highlight the complex interplay between the polar, non-polar and charged molecular interactions that exist in the system.

Bowron, D T

2004-01-01

160

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.

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

161

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.

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

2013-01-01

162

Problems of the structure of aqueous solutions of electrolytes. 2. Volume properties of solutions and their structure  

Microsoft Academic Search

Conclusions 1.The experimental material on the volume properties of solutions of electrolytes can be generalized and systematized on the basis of the developed structural model of the accommodation of ions and hydrate complexes in solution.2.Geometrical models of the structure of solutions of a large number of electrolytes (about 100 electrolytes), explaining the entire variety of volume effects in solutions in

A. K. Lyashchenko

1975-01-01

163

Bridging the solution divide: comprehensive structural analyses of dynamic RNA, DNA, and protein assemblies by small angle X-ray scattering  

PubMed Central

Summary Small-Angle X-ray Scattering (SAXS) is changing how we perceive biological structures, because it reveals dynamic macromolecular conformations and assemblies in solution. SAXS information captures thermodynamic ensembles, enhances static structures detailed by high-resolution methods, uncovers commonalities among diverse macromolecules, and helps define biological mechanisms. SAXS-based experiments on RNA riboswitches and ribozymes and on DNA-protein complexes including DNA-PK and p53 discover flexibilities that better define structure-function relationships. Furthermore, SAXS results suggest conformational variation is a general functional feature of macromolecules. Thus, accurate structural analyses will require a comprehensive approach that assesses both flexibility, as seen by SAXS, and detail, as determined by X-ray crystallography and NMR. Here, we review recent SAXS computational tools, technologies, and applications to nucleic acids and related structures.

Rambo, Robert P.; Tainer, John A.

2010-01-01

164

Subtilisin Increases Macromolecular Efflux from the Oral Mucosa  

PubMed Central

The purpose of this study was to determine whether subtilisin, a potent serine proteinase derived from Bacillus species contaminating smokeless tobacco, increases macromolecular efflux from the oral mucosa and, if so, whether local elaboration of bradykinin mediates this response. Using intravital microscopy, I found that suffusion of subtilisin elicits significant, concentration-dependent leaky site formation and an increase in the clearance of fluorescein isothiocyanate-labeled dextran (molecular mass, 70 kDa) from the in situ hamster cheek pouch (P < 0.05). Heat-inactivated subtilisin had no significant effects on macromolecular efflux. Subtilisin-induced responses were significantly attenuated by Hoe 140 and NPC 17647, two structurally distinct selective bradykinin B2 receptor antagonists, but not by des-Arg9-[Leu8]bradykinin, a selective bradykinin B1 receptor antagonist, or CP-96,345, a selective neurokinin-1 receptor antagonist. Aprotinin, but not leupeptin, significantly attenuated subtilisin-induced increase in macromolecular efflux. Indomethacin had no significant effects on subtilisin-induced responses. Collectively, these data indicate that subtilisin increases the macromolecular efflux from the in situ hamster cheek pouch in a catalytic-site-dependent fashion through local elaboration of bradykinin. This response does not involve the stimulation of local afferent nerves or the production of prostaglandins.

Rubinstein, Israel

2000-01-01

165

Macromolecular Crystal Quality  

NASA Technical Reports Server (NTRS)

There are many ways of judging a good crystal. Which we use depends on the qualities we seek. For gemstones size, clarity and impurity levels (color) are paramount. For the semiconductor industry purity is probably the most important quality. For the structural crystallographer the primary desideratum is the somewhat more subtle concept of internal order. In this chapter we discuss the effect of internal order (or the lack of it) on the crystal's diffraction properties.

Snell, Edward H.; Borgstahl, Gloria E. O.; Bellamy, Henry D.; Curreri, Peter A. (Technical Monitor)

2001-01-01

166

Structure of void space in polymer solutions  

NASA Astrophysics Data System (ADS)

The structure of void space in two- and three-dimensional (3D) polymer solutions is studied using Voronoi tessellation and percolation theory. The polymer molecules are modeled as freely jointed chains of N tangent hard disks (two dimensions) or spheres (three dimensions). Polymer chains are equilibrated via Monte Carlo simulations and the pore space in configurations of equilibrated chains is mapped using Voronoi tessellation. In d dimensions a Voronoi vertex is the center of the sphere tangent to the d+1 nearest monomers. An edge of the Voronoi diagram is the shortest route between two neighboring vertices. The edge is considered connected if a monomer can pass through and disconnected otherwise. The Voronoi construction is used to calculate the percolation threshold of the void space. The most interesting result is that the polymer area fraction at the percolation threshold is a nonmonotonic function of N in two dimensions but monotonically reaches a constant value in three dimensions. The crossover behavior of the percolation threshold is also observed in pseudo-3D. The pore size distribution decreases monotonically with increasing pore size. This is markedly different from that in configurations of hard disks (monomeric fluid) where the pore size distribution is peaked at finite size.

Sung, Bong June; Yethiraj, Arun

2010-03-01

167

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

168

Structure of void space in polymer solutions.  

PubMed

The structure of void space in two- and three-dimensional (3D) polymer solutions is studied using Voronoi tessellation and percolation theory. The polymer molecules are modeled as freely jointed chains of N tangent hard disks (two dimensions) or spheres (three dimensions). Polymer chains are equilibrated via Monte Carlo simulations and the pore space in configurations of equilibrated chains is mapped using Voronoi tessellation. In d dimensions a Voronoi vertex is the center of the sphere tangent to the d+1 nearest monomers. An edge of the Voronoi diagram is the shortest route between two neighboring vertices. The edge is considered connected if a monomer can pass through and disconnected otherwise. The Voronoi construction is used to calculate the percolation threshold of the void space. The most interesting result is that the polymer area fraction at the percolation threshold is a nonmonotonic function of N in two dimensions but monotonically reaches a constant value in three dimensions. The crossover behavior of the percolation threshold is also observed in pseudo-3D. The pore size distribution decreases monotonically with increasing pore size. This is markedly different from that in configurations of hard disks (monomeric fluid) where the pore size distribution is peaked at finite size. PMID:20365759

Sung, Bong June; Yethiraj, Arun

2010-03-01

169

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.

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

2012-01-01

170

Analytical solution for the structure of ADAFs  

NASA Astrophysics Data System (ADS)

The standard advection-dominated accretion flow (ADAF) is studied using a set of self-similar analytical solutions in spherical coordinates. Our new solutions are useful for studying ADAFs without dealing with the usual mathematical complexity. We assume that the r? component of the stress tensor dominates and the latitudinal component of the velocity is negligible; moreover, the fluid is incompressible and the solutions are radially self-similar. We show that our analytical solutions display most of the important properties of ADAFs that have already been obtained through detailed numerical solutions. According to our solutions, the density and pressure of the flow decrease from the equator to the polar regions and this reduction depends on the amount of advected energy. We also show analytically that an ADAF tends to a quasi-spherical configuration as more energy is advected with the radial flow.

Shadmehri, Mohsen

2014-08-01

171

Macromolecular ion accelerator mass spectrometer.  

PubMed

We present a newly developed macromolecular ion accelerator mass spectrometer that combines a dual-ion-trap device and a macromolecular ion accelerator (MIA) to achieve the capability of analyzing samples with a mixture of large biomolecules. MIA greatly increases detection efficiency. The dual ion trap includes a quadrupole ion trap (QIT) and a linear ion trap (LIT) in tandem. The dual ion trap is mounted ahead of the MIA. The QIT is used to store multiple species, and the LIT is employed to capture the ions that are sequentially ejected out of the QIT. Subsequent to their capture, the ions inside of the LIT are extracted and transferred to the MIA. The synchronization between the QIT and MIA is bridged by the LIT. A sample containing a mixture of several large biomolecules was employed to examine the performance of this new type of mass spectrometer. The result reveals that larger biomolecules show a comparable signal to smaller biomolecules, even though the mixture contains equal quantities of each type of protein. The overall assembly produces a nearly constant detection efficiency over a broad mass range. Thus, this device provides an alternative platform to analyze complex large-protein mixtures. PMID:24171190

Hsu, Yun-Fei; Lin, Jung-Lee; Chu, Ming-Lee; Wang, Yi-Sheng; Chen, Chung-Hsuan

2013-11-12

172

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.

Weik, Martin; Colletier, Jacques-Philippe

2010-01-01

173

Solution NMR of Large Molecules and Assemblies †  

Microsoft Academic Search

Solution NMR spectroscopy represents a powerful tool for examining the structure and function of biological macromolecules. The advent of multidimensional (2D-4D) NMR, together with the widespread use of uniform isotopic labeling of proteins and RNA with the NMR-active isotopes, 15N and 13C, opened the door to detailed analyses of macromolecular structure, dynamics, and interactions of smaller macromolecules (<25 kDa). Over

Mark P. Foster; Craig A. McElroy; Carlos D. Amero

2007-01-01

174

Organo-macromolecular transport relationships for argillaceous membranes at ultra-high hydraulic gradients  

Microsoft Academic Search

Empirically derived parameters and analytical solutions were used to determine possible mechanistic processes of organo-macromolecular fate in dead-end hyperfiltration at abnormal hydraulic pressure settings. Ideally the concentration polarization is assumed to have an ideal geometry but this may not be so since preferential flow paths in an experimental setup limits this. Most analytical solutions also tend to support this idealized

Peter G. Oduor; P. Gibbs; X. Santos; A. Podoll; J. Dunham

2009-01-01

175

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

176

Local structural heterogeneity in garnet solid solutions  

Microsoft Academic Search

Local heterogeneities in pyrope-almandine, almandine-grossular and pyrope-grossular solid solutions have been investigated using IR-powder absorption spectroscopy. Correlations of the wavenumber shifts and line broadening systematics with the thermodynamic mixing properties were found. Wavenumber shifts of the highest energy modes correlate closely with the Si-O bond distances and give an indirect view of the average distortions across the three solid solutions.

T. Boffa Ballaran; M. A. Carpenter; C. A. Geiger; A. M. Koziol

1999-01-01

177

Local structural heterogeneity in garnet solid solutions  

Microsoft Academic Search

Local heterogeneities in pyrope-almandine, almandine-grossular and pyrope-grossular solid solutions have been investigated\\u000a using IR-powder absorption spectroscopy. Correlations of the wavenumber shifts and line broadening systematics with the thermodynamic\\u000a mixing properties were found. Wavenumber shifts of the highest energy modes correlate closely with the Si-O bond distances\\u000a and give an indirect view of the average distortions across the three solid solutions.

T. Boffa Ballaran; M. A. Carpenter; C. A. Geiger; A. M. Koziol

1999-01-01

178

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

179

Molecular Simulations of Concentrated Aqueous Solutions: Ionic Equilibrium Structures in Solutions.  

National Technical Information Service (NTIS)

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 ...

K. Wolf M. Zapolowski W. M. Bartczak

2001-01-01

180

Dielectric properties and structure of aqueous solutions of boric acid  

Microsoft Academic Search

A model of the,structure of aqueous boric acid solution has been constructed, based on the view that the acid molecules are inserted into the ice-like lattice of water. The model predicts the rupture of a certain number of hydrogen bonds in the water structure. Themodel agrees withdata on the density and the dielectric constant of the solution at superhigh frequencies.

A. K. Lyashchenko; V. S. Goncharov; P. S. Yastremskii

1977-01-01

181

Novel Solution Methods for Nonlinear Structural Dynamics  

NASA Astrophysics Data System (ADS)

Nonlinear oscillations are present in many physical systems in science and engineering. Through simplifying assumptions, many systems can be reduced to various forms of the venerable Duffing equation. Three examples of physical systems that can be reduced to Duffing's equation are a clamped-clamped beam, von Karman's plate equations, and the pitch-plunge model for an airfoil in steady incompressible flow. These models will be examined in detail. Specifically, an approach to general n-DOF Spring-Mass-Damper (SMD) models will be the culmination. Some forms of the Duffing equation have exact solutions but that is more an exception than a rule. Some exact solutions will be examined but the majority of the discussion will focus on approximate solutions where closed form solutions do not exist. The method of weighted residuals will be applied to transform Duffing's 2nd order nonlinear ODE into a system of nonlinear algebraic equations (NAEs). Various features of different methods will be discussed to solve the system of NAEs. Several aspects of nonlinear systems in the context of the solution methods will be discussed including: jump phenomena, dependence on initial conditions, super and subharmonics, stability and the approach to chaotic motion.

Schnoor, Matthew

182

Effect of macromolecular impurities on lysozyme solubility and crystallizability: dynamic light scattering, phase diagram, and crystal growth studies  

NASA Astrophysics Data System (ADS)

The effects of macromolecular impurities on protein solubility and crystallizability were investigated by dynamic light scattering and crystal growth experiments using hen egg-white lysozyme as the model protein. In the presence of traces of protein impurities, representing no more than 2% (w/w) of the total protein, the average diffusion coefficients of the macromolecular particles found in undersaturated lysozyme solutions are significantly lower than those measured with purest lysozyme preparations. This fact is explained by the simultaneous existence of individual molecules and of large size aggregates in contaminated solutions, as indicated by the bimodal light scattering autocorrelation function. Controlled contamination experiments in which ovalbumin or conalbumin were added to purest lysozyme indicate that aggregates result from heterogeneous association of lysozyme molecules with the structurally unrelated proteins. These aggregates might become starting points for heterogeneous nucleation leading to the growth of ill-shaped microcrystals. Aggregates in under- or supersaturated lysozyme solutions containing NaCl can be eliminated by filtration over microporous membranes. As a result the number of ill-shaped crystals diminishes drastically; that of well-shaped tetragonal crystals decreases also but their size increases.

Skouri, M.; Lorber, B.; Giegé, R.; Munch, J.-P.; Candau, J. S.

1995-07-01

183

WAXS studies of the structural diversity of hemoglobin in solution.  

SciTech Connect

Specific ligation states of hemoglobin are, when crystallized, capable of taking on multiple quaternary structures. The relationship between these structures, captured in crystal lattices, and hemoglobin structure in solution remains uncertain. Wide-angle X-ray solution scattering (WAXS) is a sensitive probe of protein structure in solution that can distinguish among similar structures and has the potential to contribute to these issues. We used WAXS to assess the relationships among the structures of human and bovine hemoglobins in different liganded forms in solution. WAXS data readily distinguished among the various forms of hemoglobins. WAXS patterns confirm some of the relationships among hemoglobin structures that have been defined through crystallography and NMR and extend others. For instance, methemoglobin A in solution is, as expected, nearly indistinguishable from HbCO A. Interestingly, for bovine hemoglobin, the differences between deoxy-Hb, methemoglobin and HbCO are smaller than the corresponding differences in human hemoglobin. WAXS data were also used to assess the spatial extent of structural fluctuations of various hemoglobins in solution. Dynamics has been implicated in allosteric control of hemoglobin, and increased dynamics has been associated with lowered oxygen affinity. Consistent with that notion, WAXS patterns indicate that deoxy-Hb A exhibits substantially larger structural fluctuations than HbCO A. Comparisons between the observed WAXS patterns and those predicted on the basis of atomic coordinate sets suggest that the structures of Hb in different liganded forms exhibit clear differences from known crystal structure.

Makowski, L.; Bardhan, J.; Gore, D.; Lal, J.; Mandava, S.; Park, S.; Rodi, D. J.; Ho, N. T.; Ho, C.; Fischetti, R. F. (Biosciences Division); ( MCS); (Northeastern Univ.); (Illinois Inst. of Tech.); (Carnegie Mellon Univ.)

2011-01-01

184

Biophysical highlights from 54 years of macromolecular crystallography.  

PubMed

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

2014-02-01

185

Visual automated macromolecular model building  

PubMed Central

Automated model-building software aims at the objective interpretation of crystallographic diffraction data by means of the construction or completion of macromolecular models. Automated methods have rapidly gained in popularity as they are easy to use and generate reproducible and consistent results. However, the process of model building has become increasingly hidden and the user is often left to decide on how to proceed further with little feedback on what has preceded the output of the built model. Here, ArpNavigator, a molecular viewer tightly integrated into the ARP/wARP automated model-building package, is presented that directly controls model building and displays the evolving output in real time in order to make the procedure transparent to the user.

Langer, Gerrit G.; Hazledine, Saul; Wiegels, Tim; Carolan, Ciaran; Lamzin, Victor S.

2013-01-01

186

NMR Studies of Aqueous Solution Structure.  

National Technical Information Service (NTIS)

Nmr chemical shifts and linewidths are reported for eleven substituted ureas and related compounds as a function of pH in aqueous solution. The effect of various added electrolytes on proton exchange rates and nitrogen relaxation rates is determined. Tren...

R. L. Vold

1973-01-01

187

Imaging the structure of water near hydrophobic solutes  

NASA Astrophysics Data System (ADS)

Theoretical studies of the structure of interfacial water on the surface of hydrophobic solutes show a strong dependence on the radius of the solute itself. At small radii, a hydrogen-bond network is still capable of forming around the solute, generally forbidding association between the solute molecules. At large radii water can no longer form a hydrogen-bond network around the solute molecule, resulting in the ``drying'' of the surface and a strong attraction between solute molecules. The crossover length between the two regimes is on the order of a nanometer. We will show that it is possible to make movies of water around hydrophobic solutes of varying size by extracting the density propagator from the dynamical structure factor measured via high-resolution inelastic x-ray scattering spectra at 3rd generation synchrotron sources.

Wong, Gerard C. L.; Coridan, Robert H.; Hwee Lai, Ghee; Schmidt, Nathan S.; Krisch, Michael; Abbamonte, Peter

2007-03-01

188

Structure of gum arabic in aqueous solution  

Microsoft Academic Search

Gum arabic, a natural polysaccharide derived from exudates of Acacia senegal and Acacia seyal trees, is a commonly used food hydrocolloid. The complex chemical structure of the gum has been widely studied revealing a multifraction ma- terial consisting mainly of a highly branched polysaccharide and a protein-polysac- charide complex (GAGP) as a minor component. This work investigates its mesoscopic structure

Yael Dror; Yachin Cohen; Rachel Yerushalmi-Rozen

2006-01-01

189

Solution Structure of the Cyclotide Palicourein  

Microsoft Academic Search

The cyclotides are a family of disulfide-rich proteins from plants. They have the characteristic structural features of a circular protein backbone and a knotted arrangement of disulfide bonds. Structural and biochemical studies of the cyclotides suggest that their unique physiological stability can be loaned to bioactive peptide fragments for pharmaceutical and agricultural development. In particular, the cyclotides incorporate a number

Daniel G Barry; Norelle L Daly; Heidi R Bokesch; Kirk R Gustafson; David J Craik

2004-01-01

190

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.

Rosgen, Jorg; Pettitt, B. Montgomery; Bolen, David Wayne

2005-01-01

191

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

192

On the Origin of Macromolecular Sequences  

PubMed Central

The origin of the degree and type of order found in biological macromolecules is not adequately explained solely as an accumulation of genetic restrictions acquired through natural selection from otherwise unrestricted primeval sequences capable of self-replication, since the biological process of replication is itself dependent on the pre-existence of such order, and since the number of sequences that could have ever been tested by selection on the earth is an insignificant fraction of the number of unrestricted sequences which would be possible. Therefore the hypothesis is considered that replication and selection began from well ordered sequences, rather than random sequences. It is shown how the Turing concept of computation in fed-back, discrete-state automata can lead to the generation of order withour pre-existing instructions, and how this computation can result in self-repeating, random-like, but well ordered sequences of great length. Macromolecular models of such computers are suggested on the basis of mechanisms proposed for the growth of eutactic polymers. Such self-replicating, mutable sequences may then evolve genetic control which is sufficient to accommodate the information accumulated by natural selection. The structure and function of enzymes and structural proteins is related to this model, and statistical evidence from known amino acid sequences is shown to be consistent with some degree of non-genetic ordering.

Pattee, Howard H.

1961-01-01

193

Adaptation to extreme environments: macromolecular dynamics in complex systems.  

PubMed

What we previously thought of as insurmountable physical and chemical barriers to life, we now see as yet another niche harbouring 'extremophiles'. Extremophiles and their macromolecules had to develop molecular mechanisms of adaptation to extreme physico-chemical conditions. Using neutron spectroscopy, we have demonstrated that molecular dynamics represents one of these molecular mechanisms of adaptation. To which extent do hyper-saline conditions and extreme temperatures influence molecular dynamics? First, molecular dynamics were analysed for halophilic malate dehydrogenase from Haloarcula marismortui (Hm MalDH) under different molar solvent salt concentration conditions influencing its stability. Secondly, mean macromolecular motions were measured in-vivo in psychrophile (Aquaspirillum arcticum), mesophile (Escherichia coli and Proteus mirabilis), thermophile (Thermus thermophilus), and hyperthermophile (Aquifex pyrofilus) bacteria. The mean constant force of Hm MalDH increases progessively with increasing stability. The results show that the molecular adaptation of Hm MalDH to hyper-saline conditions is achieved through an increasing resilience of its structure dominated by enthalpic mechanisms. The study of bacteria has provided tools to quantify the macromolecular adaptation to extreme temperatures in the naturally crowded environment of the cell. The macromolecular resilience of bacteria increases with adaptation to high temperatures. PMID:15951115

Tehei, Moeava; Zaccai, Giuseppe

2005-08-01

194

Dilute Bicellar Solutions for Structural NMR Work  

NASA Astrophysics Data System (ADS)

Deuterium NMR spectroscopy has been employed to characterize the concentration dependence of orientational order in DMPC/DHPC bicellar solutions with molar ratios q= [DMPC]/[DHPC] = 3.3, 2.7, and 2.3. The stability of a discotic nematic phase can, in general, be predicted from a simple Onsager picture involving the size and concentration of the mesogenic unit, but for the bicellar solutions this model is not adequate. Specifically, macroscopic alignment is observed at total lipid concentrations well below that, 1-10% (w/w) predicted by Onsager's model. Thus the discotic nematic phase is stable to ?3-5% (w/w) for q= 3.3-2.3, and the bicellar order is highest just before phase separation occurs at the minimum total phospholipid concentration. This implies the presence of a DHPC bic? DHPC solequilibrium in establishing bicellar size, thereby extending the range of concentrations for which alignment occurs. Bicellar morphology has been verified for a wide range of concentrations, temperatures, and q-values, but as viscosity measurements demonstrate, major morphological changes take place as the temperature is reduced below 30°C.

Struppe, Jochem; Vold, Regitze R.

1998-12-01

195

Solution processed organic microarray with inverted structure  

NASA Astrophysics Data System (ADS)

We have fabricated inverted organic microarray using a novel solution-based technique. The array consists of 60 small (1 square mm) solar cells on a one inch by one inch glass substrate. The device utilizes photoactive materials such as a blend of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM). Manipulation of active layer nanomorphology has been done by choice of solvents and annealing conditions. Detailed analysis of device physics including current voltage characteristics, external quantum efficiency and carrier recombinations will be presented and complimented by AFM images and glazing angle XRD of the active layer under different processing conditions. The procedure described here has the full potential for use in future fabrication of microarrays with single cell as small as 0.01 square mm for application in DC power supplies for electrostatic Microelectromechanical systems (MEMS) devices.

Toglia, Patrick; Lewis, Jason; Lafalce, Evan; Jiang, Xiaomei

2011-03-01

196

Solution structure of calcium-free calmodulin.  

PubMed

The three-dimensional structure of calmodulin in the absence of Ca2+ has been determined by three- and four-dimensional heteronuclear NMR experiments, including ROE, isotope-filtering combined with reverse labelling, and measurement of more than 700 three-bond J-couplings. In analogy with the Ca(2+)-ligated state of this protein, it consists of two small globular domains separated by a flexible linker, with no stable, direct contacts between the two domains. In the absence of Ca2+, the four helices in each of the two globular domains form a highly twisted bundle, capped by a short anti-parallel beta-sheet. This arrangement is qualitatively similar to that observed in the crystal structure of the Ca(2+)-free N-terminal domain of troponin C. PMID:7552748

Kuboniwa, H; Tjandra, N; Grzesiek, S; Ren, H; Klee, C B; Bax, A

1995-09-01

197

The promise of macromolecular crystallization in microfluidic chips  

NASA Technical Reports Server (NTRS)

Microfluidics, or lab-on-a-chip technology, is proving to be a powerful, rapid, and efficient approach to a wide variety of bioanalytical and microscale biopreparative needs. The low materials consumption, combined with the potential for packing a large number of experiments in a few cubic centimeters, makes it an attractive technique for both initial screening and subsequent optimization of macromolecular crystallization conditions. Screening operations, which require a macromolecule solution with a standard set of premixed solutions, are relatively straightforward and have been successfully demonstrated in a microfluidics platform. Optimization methods, in which crystallization solutions are independently formulated from a range of stock solutions, are considerably more complex and have yet to be demonstrated. To be competitive with either approach, a microfluidics system must offer ease of operation, be able to maintain a sealed environment over several weeks to months, and give ready access for the observation and harvesting of crystals as they are grown.

van der Woerd, Mark; Ferree, Darren; Pusey, Marc

2003-01-01

198

Large Structures: which Solutions for Health Monitoring?  

NASA Astrophysics Data System (ADS)

Whatever the age of a large structure (dam, viaduct, cooling tower, nuclear containment, tunnel, …) It has to be periodically monitored. It is a challenge to realise these services when the access is limited and difficult for Man. This paper introduces a global approach, developed by SITES, through examples of application on different concrete dams or cooling towers, and their results. This global method involves three techniques: the SCANSITES® (a visual inspection system), the LIDAR (3D laser scanning) and high resolution photogrammetry.

Camp, G.; Carreaud, P.; Lançon, H.

2013-07-01

199

Structural modification of supersaturated BCC-Nd(Al) solid solution  

Microsoft Academic Search

The metastable Nd(Al) supersaturated solid solution with the BCC structure was synthesized by the melt-spinning method. The thermal stability of the supersaturated solid solution was studied by differential scanning calorimetry (DSC) and electrical-resistance measurements. The structural modification was determined by X-ray diffraction (XRD) and transmission electron microscopy (TEM). A constrained BCC lattice was found due to the smaller Al atoms

W. S. Sun; E. D. Wu; H. F. Zhang; Z. Q. Hu

2005-01-01

200

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

201

Automated error-tolerant macromolecular structure determination from multidimensional nuclear Overhauser enhancement spectra and chemical shift assignments: improved robustness and performance of the PASD algorithm.  

PubMed

We report substantial improvements to the previously introduced automated NOE assignment and structure determination protocol known as PASD (Kuszewski et al. (2004) J Am Chem Soc 26:6258-6273). The improved protocol includes extensive analysis of input spectral data to create a low-resolution contact map of residues expected to be close in space. This map is used to obtain reasonable initial guesses of NOE assignment likelihoods which are refined during subsequent structure calculations. Information in the contact map about which residues are predicted to not be close in space is applied via conservative repulsive distance restraints which are used in early phases of the structure calculations. In comparison with the previous protocol, the new protocol requires significantly less computation time. We show results of running the new PASD protocol on six proteins and demonstrate that useful assignment and structural information is extracted on proteins of more than 220 residues. We show that useful assignment information can be obtained even in the case in which a unique structure cannot be determined. PMID:18668206

Kuszewski, John J; Thottungal, Robin Augustine; Clore, G Marius; Schwieters, Charles D

2008-08-01

202

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.

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

2011-01-01

203

Iterative elastic 3D-to-2D alignment method using normal modes for studying structural dynamics of large macromolecular complexes.  

PubMed

This article presents a method to study large-scale conformational changes by combining electron microscopy (EM) single-particle image analysis and normal mode analysis (NMA). It is referred to as HEMNMA, which stands for hybrid electron microscopy normal mode analysis. NMA of a reference structure (atomic-resolution structure or EM volume) is used to predict possible motions that are then confronted with EM images within an automatic iterative elastic 3D-to-2D alignment procedure to identify actual motions in the imaged samples. HEMNMA can be used to extensively analyze the conformational changes and may be used in combination with classic discrete procedures. The identified conformations allow modeling of deformation pathways compatible with the experimental data. HEMNMA was tested with synthetic and experimental data sets of E. coli 70S ribosome, DNA polymerase Pol ? and B subunit complex of the eukaryotic primosome, and tomato bushy stunt virus. PMID:24508340

Jin, Qiyu; Sorzano, Carlos Oscar S; de la Rosa-Trevín, José Miguel; Bilbao-Castro, José Román; Núñez-Ramírez, Rafael; Llorca, Oscar; Tama, Florence; Joni?, Slavica

2014-03-01

204

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.

2014-01-01

205

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

206

NMR solution structures of LNA (locked nucleic acid) modified quadruplexes  

Microsoft Academic Search

We have determined the NMR solution structures of the quadruplexes formed by d(TGLGLT) and d(TL4T), where L denotes LNA (locked nucleic acid) modified G-residues. Both structures are tetrameric, parallel and right-handed and the native global fold of the corresponding DNA quadruplex is retained upon introduction of the LNA nucleotides. However, local structural alterations are observed owing to the locked LNA

Jakob T. Nielsen; Khalil Arar; Michael Petersen

2006-01-01

207

Solution processed microcavity structures with embedded quantum dots  

Microsoft Academic Search

The authors report the fabrication of a one-dimensional microcavity structure embedded with colloidal CdSe\\/ZnS core\\/shell quantum dots using solution processing. The microcavity structures were fabricated by spin coating alternating layers of polymers of different refractive indices (poly-vinylcarbazole—PVK, and poly-acrylic acid—PAA) to form the distributed Bragg reflectors (DBRs). Greater than 90% reflectivity was obtained using ten periods of the structure. The

N. Valappil; M. Luberto; V. M. Menon; I. Zeylikovich; T. K. Gayen; J. Franco; B. B. Das; R. R. Alfano

2007-01-01

208

Effect of polydispersity on the structure factor of a melt of binary multiblock copolymers with a two-length-scale macromolecular architecture  

NASA Astrophysics Data System (ADS)

A theoretical study on the effect of polydispersity of two-length-scale binary multiblock copolymers on the shape of the structure factor is presented. A bifurcation diagram is constructed showing the partition of the parameter space into domains differing in the way in which the homogeneous melt loses thermodynamic stability. When the polydispersity of the two-length-scale multiblock copolymers is high enough the phase diagram may contain a surface of double spinodal points separating regions of trivial and nontrivial spinodal branches. The information about the location of these regions is an indispensable prerequisite for the construction of a phase diagram, because the type of temperature-induced phase transition caused by the loss of thermodynamic stability of the homogeneous state depends on the range of values of the block copolymer parameters.

Kuchanov, S.; Zharnikov, T.; ten Brinke, G.

2011-11-01

209

Bringing single-molecule spectroscopy to macromolecular protein complexes  

PubMed Central

Single-molecule fluorescence spectroscopy offers real-time, nanometer-resolution information. Over the past two decades, this emerging single-molecule technique has been rapidly adopted to investigate the structural dynamics and biological functions of proteins. Despite this remarkable achievement, single-molecule fluorescence techniques must be extended to macromolecular protein complexes that are physiologically more relevant for functional studies. In this review, we present recent major breakthroughs for investigating protein complexes within cell extracts using single-molecule fluorescence. We outline the challenges, future prospects and potential applications of these new single-molecule fluorescence techniques in biological and clinical research.

Joo, Chirlmin; Fareh, Mohamed; Kim, V. Narry

2013-01-01

210

Solution Growth and Structures of Semiconducting Distyryl-Oligothiophene  

Microsoft Academic Search

Large single crystals of 5,5?-distyryl-2,2?-bithiophene (DS-2T) were grown from tetrahydrofurane (THF) solution, and the crystal structure was analyzed by x-ray diffractometry. In-situ observation of crystal growth in solution was performed, and a unique change in the crystal habit depending on growth conditions is found. The change in crystal habit from a truncated parallelogram shape to a slender hexagonal shape with

M. Ito; W. Y. Li; N. Yoshimoto; H. Muraoka; S. Ogawa; H. Fujishiro; Y. Asabe; J. Ackermann; H. Brisset; F. Fages

2008-01-01

211

Water structure in aqueous solutions of tetramethylammonium chloride  

Microsoft Academic Search

Neutron diffraction with hydrogen\\/deuterium isotope substitution is used to investigate the water structure and the solute distribution in aqueous solutions of tetramethylammonium chloride ((CH3)4NCl) between 2·0 and 8·0m concentrations at room temperature. The hydrogen-hydrogen (HH) pair correlation functions for the water indicate that the hydrogen-bonding geometry is not significantly changed over the concentration range compared to pure water, although the

J. Turner; A. K. Soper; J. L. Finney

1992-01-01

212

Characterization of Chitin and Chitosan Molecular Structure in Aqueous Solution  

Microsoft Academic Search

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

Eduardo D. Franca; Roberto D. Lins; Luiz C. G. Freitas; T. P. Straatsma

2008-01-01

213

Structural analysis of 5-fluorouracil and thymine solid solutions  

NASA Astrophysics Data System (ADS)

Solid-state analysis with powder X-ray diffraction (PXRD), solid-state NMR (SSNMR), and other spectroscopic and physical methods can provide detailed structural information about organic and pharmaceutical cocrystals. In this study, a range of solid-state analysis methods are used to characterize co-crystallized solid solutions of 5-fluorouracil and thymine. 1H, 13C and 19F SSNMR and PXRD methods are used to study the structure and disorder present in a solid solution previously prepared by solution evaporation methods; here the solid solution is prepared over a wider stoichiometric range by solvent-drop grinding techniques. Long-range perturbations of key chemical shifts are detectable by SSNMR, indicating that the solid solution is not random. Cross-polarization and heteronuclear correlation SSNMR experiments between 1H, 13C, and 19F nuclei offer insight into the structure of this solid solution, and density functional theory (DFT) methods are applied to calculate lattice energies and NMR properties in order to understand the population of the two primary disordered sites in the crystal structure. In addition, a second solid solution of 5-fluorouracil and thymine is reported and analyzed. This solid solution, which was produced by solvent-drop grinding experiments and characterized by SSNMR and powder X-ray diffraction methods, is determined to be an isostructural phase to that of anhydrous thymine with the inclusion of 5-fluorouracil defects. A similar effect does not occur under excess 5-fluorouracil conditions; instead, phase-separated Form 1 of 5-fluorouracil and anhydrous thymine are obtained. DFT calculations are applied to offer a possible explanation for this disparity.

Vogt, Frederick G.; Vena, Joseph A.; Chavda, Manisha; Clawson, Jacalyn S.; Strohmeier, Mark; Barnett, Maria E.

2009-08-01

214

The Contrasting Effect of Macromolecular Crowding on Amyloid Fibril Formation  

PubMed Central

Background Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms. It is known that in vivo human Tau protein, human prion protein, and human copper, zinc superoxide dismutase (SOD1) have the tendency to form fibril deposits in a variety of tissues and they are associated with different neurodegenerative diseases, while rabbit prion protein and hen egg white lysozyme do not readily form fibrils and are unlikely to cause neurodegenerative diseases. In this study, we have investigated the contrasting effect of macromolecular crowding on fibril formation of different proteins. Methodology/Principal Findings As revealed by assays based on thioflavin T binding and turbidity, human Tau fragments, when phosphorylated by glycogen synthase kinase-3?, do not form filaments in the absence of a crowding agent but do form fibrils in the presence of a crowding agent, and the presence of a strong crowding agent dramatically promotes amyloid fibril formation of human prion protein and its two pathogenic mutants E196K and D178N. Such an enhancing effect of macromolecular crowding on fibril formation is also observed for a pathological human SOD1 mutant A4V. On the other hand, rabbit prion protein and hen lysozyme do not form amyloid fibrils when a crowding agent at 300 g/l is used but do form fibrils in the absence of a crowding agent. Furthermore, aggregation of these two proteins is remarkably inhibited by Ficoll 70 and dextran 70 at 200 g/l. Conclusions/Significance We suggest that proteins associated with neurodegenerative diseases are more likely to form amyloid fibrils under crowded conditions than in dilute solutions. By contrast, some of the proteins that are not neurodegenerative disease-associated are unlikely to misfold in crowded physiological environments. A possible explanation for the contrasting effect of macromolecular crowding on these two sets of proteins (amyloidogenic proteins and non-amyloidogenic proteins) has been proposed.

Zhou, Zheng; Zhou, Bing-Rui; Meng, Sheng-Rong; Hu, Ji-Ying; Chen, Jie; Liang, Yi

2012-01-01

215

[Macromolecular aromatic network characteristics of Chinese power coal analyzed by synchronous fluorescence and X-ray diffraction].  

PubMed

Coal structure, especially the macromolecular aromatic skeleton structure, has a strong influence on coke reactivity and coal gasification, so it is the key to grasp the macromolecular aromatic skeleton coal structure for getting the reasonable high efficiency utilization of coal. However, it is difficult to acquire their information due to the complex compositions and structure of coal. It has been found that the macromolecular aromatic network coal structure would be most isolated if small molecular of coal was first extracted. Then the macromolecular aromatic skeleton coal structure would be clearly analyzed by instruments, such as X-ray diffraction (XRD), fluorescence spectroscopy with synchronous mode (Syn-F), Gel permeation chromatography (GPC) etc. Based on the previous results, according to the stepwise fractional liquid extraction, two Chinese typical power coals, PS and HDG, were extracted by silica gel as stationary phase and acetonitrile, tetrahydrofuran (THF), pyridine and 1-methyl-2-pyrollidinone (NMP) as a solvent group for sequential elution. GPC, Syn-F and XRD were applied to investigate molecular mass distribution, condensed aromatic structure and crystal characteristics. The results showed that the size of aromatic layers (La) is small (3-3.95 nm) and the stacking heights (Lc) are 0.8-1.2 nm. The molecular mass distribution of the macromolecular aromatic network structure is between 400 and 1 130 amu, with condensed aromatic numbers of 3-7 in the structure units. PMID:23016368

Ye, Cui-Ping; Feng, Jie; Li, Wen-Ying

2012-07-01

216

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.

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

2013-01-01

217

Progress in rational methods of cryoprotection in macromolecular crystallography  

PubMed Central

Cryogenic cooling of macromolecular crystals is commonly used for X-ray data collection both to reduce crystal damage from radiation and to gather functional information by cryogenically trapping intermediates. However, the cooling process can damage the crystals. Limiting cooling-induced crystal damage often requires cryoprotection strategies, which can involve substantial screening of solution conditions and cooling protocols. Here, recent developments directed towards rational methods for cryoprotection are described. Crystal damage is described in the context of the temperature response of the crystal as a thermodynamic system. As such, the internal and external parts of the crystal typically have different cryoprotection requirements. A key physical parameter, the thermal contraction, of 26 different cryoprotective solutions was measured between 294 and 72?K. The range of contractions was 2–13%, with the more polar cryosolutions contracting less. The potential uses of these results in the development of cryocooling conditions, as well as recent developments in determining minimum cryosolution soaking times, are discussed.

Alcorn, Thomas; Juers, Douglas H.

2010-01-01

218

Macromolecular crystallography radiation damage research: what's new?  

PubMed Central

Radiation damage in macromolecular crystallography has become a mainstream concern over the last ten years. The current status of research into this area is briefly assessed, and the ten new papers published in this issue are set into the context of previous work in the field. Some novel and exciting developments emerging over the last two years are also summarized.

Garman, Elspeth F.; Weik, Martin

2011-01-01

219

Macromolecular Chromogenic Substrates for Measuring Proteinase Activity  

Microsoft Academic Search

Background: Proteinase activities are often measured using chromogenic substrates that are much smaller than physiological substrates. Methods: The hydrodynamic size of macromolecular substrates (macrosubstrates) prepared by linking small chromogenic substrates to polyethylene glycol was de- termined by gel filtration. Efficiency of macrosubstrate cleavage by proteinases and a2-macroglobulin-protein- ase complexes was monitored spectrophotometrically. Results: Macrosubstrates had hydrodynamic radii of ;20 Å,

Glen L. Hortin; Ilka Warshawsky; Maryline Laude-Sharp

2001-01-01

220

Fusing and composing macromolecular regulatory network models  

Microsoft Academic Search

Today's macromolecular regulatory network models are small compared to the amount of information known about the corresponding cellular pathways, in part because current modeling languages and tools are unable to handle significantly larger models. Most pathway models are small models of individual pathways which are relatively easy to construct and manage. The hope is someday to put these pieces together

Ranjit Randhawa; Clifford A. Shaffer; John J. Tyson

2007-01-01

221

Solution structure of Ca 2+ -free rat ?-parvalbumin (oncomodulin)  

Microsoft Academic Search

Relative to other parvalbumin isoforms, the mammalian b-parvalbumin (oncomodulin) displays attenuated divalent ion affinity. High-resolution structural data for the Ca2+-bound protein have provided little insight into the physical basis for this behavior, prompting an examination of the unliganded state. This article describes the solution structure and peptide backbone dynamics of Ca2+- free rat b-parvalbumin (b-PV). Ca2+ removal evidently provokes significant

Michael T. Henzl; John J. Tanner

2007-01-01

222

Solution Structure of LC4 Transmembrane Segment of CCR5  

Microsoft Academic Search

CC-chemokine receptor 5 (CCR5) is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1). The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescdence quenching. The LC4 structure adopts

Kazuhide Miyamoto; Kayo Togiya; John J. Rossi

2011-01-01

223

Quantitative Electron Holography of Macromolecular Structure.  

National Technical Information Service (NTIS)

The principal theme underlying this ARO-funded research is the development and application of quantitative electron-optical methods to measure polymer morphology at nano and meso length scales where traditional TEM methods based on differential heavy-elem...

M. R. Libera

2001-01-01

224

Water Structure at Air\\/Acetonitrile Aqueous Solution Interfaces  

Microsoft Academic Search

How is interfacial water organized beneath an acetonitrile monolayer at the air\\/acetonitrile aqueous solution interface? The method of vibrational sum frequency generation was used to address these issues. It was found that the different water structures expressed at different vibrational spectral regions, i.e. the \\

Yi Rao; Nicholas J. Turro; Kenneth B. Eisenthal

2009-01-01

225

Influence of Solution Structure on Hydrated Electron Reactions.  

National Technical Information Service (NTIS)

The ultra-fast, apparent second-order decay of the hydrated electron, e(-)(aq), following nanosecond duration radiation pulses in air-free alkaline solution is discussed in detail. The proposed structure and properties of H2O(+)(aq) are described and reac...

N. Klein

1971-01-01

226

The structure of aqueous solutions of tertiary butanol  

Microsoft Academic Search

Using neutron diffraction with isotopic substitution, the structures of aqueous solutions of tertiary butanol have been studied as a function of concentration. As the behaviour of this system is thought to be driven by hydrophobic interactions, particular attention was paid to the hydration of the non-polar headgroups and the nature of the intermolecular contacts. As concentration is increased from 0.06

John L. Finney; Daniel T. Bowron; Alan K. Soper

2000-01-01

227

Solution structure of the tobramycin–RNA aptamer complex  

Microsoft Academic Search

We have solved the solution structure of the aminoglycoside antibiotic tobramycin complexed with a stem-loop RNA aptamer. The 14 base loop of the RNA aptamer 'zippers up' alongside the attached stem through alignment of four mismatches and one Watson-Crick pair on complex formation. The tobramycin inserts into the deep groove centered about the mismatch pairs and is partially encapsulated between

Licong Jiang; Dinshaw J. Patel

1998-01-01

228

Protein Stabilization by Macromolecular Crowding through Enthalpy Rather Than Entropy.  

PubMed

The interior of the cell is a densely crowded environment in which protein stability is affected differently than in dilute solution. Macromolecular crowding is commonly understood in terms of an entropic volume exclusion effect based on hardcore repulsions among the macromolecules. We studied the thermal unfolding of ubiquitin in the presence of different cosolutes (glucose, dextran, poly(ethylene glycol), KCl, urea). Our results show that for a correct dissection of the cosolute-induced changes of the free energy into its enthalpic and entropic contributions, the temperature dependence of the heat capacity change needs to be explicitly taken into account. In contrast to the prediction by the excluded volume theory, we observed an enthalpic stabilization and an entropic destabilization for glucose, dextran, and poly(ethylene glycol). The enthalpic stabilization mechanism induced by the macromolecular crowder dextran was similar to the enthalpic stabilization mechanism of its monomeric building block glucose. In the case of poly(ethylene glycol), entropy is dominating over enthalpy leading to an overall destabilization. We propose a new model to classify cosolute effects in terms of their enthalpic contributions to protein stability. PMID:24888734

Senske, Michael; Törk, Lisa; Born, Benjamin; Havenith, Martina; Herrmann, Christian; Ebbinghaus, Simon

2014-06-25

229

Interactions affecting the mechanical properties of macromolecular microsphere composite hydrogels.  

PubMed

Macromolecular microsphere composite (MMC) hydrogel is a kind of tough hydrogel fabricated by using peroxidized macromolecular microspheres as polyfunctional initiating and cross-linking centers (PFICC). The contribution of chemical cross-linking (covalent bonding) and physical cross-linking (chain entanglement and hydrogen bonding) to the mechanical properties are understood by testing the hydrogels, which were swollen in water or aqueous urea solutions to different water contents. The as-prepared MMC gels exhibited moderate moduli (60-270 kPa), high fracture tensile stresses (up to 0.54 MPa), high extensibilities (up to 2500%), and high fracture energies (270-770 J m(-2)). The moduli of the swollen gels decrease dramatically, but there are no significant changes in fracture tensile strength and fracture strain, even slight increases. More interestingly, the swollen gels show much-enhanced fracture energies, higher than 2000 J m(-2). A gradual decrease in the hysteresis ratio and residual strain is also found in the cyclic tensile testing of the hydrogels that were swollen to different water contents. The covalent bonding determines the tensile strength and fracture energy of the MMC gels, whereas the physical entanglement and hydrogen bonding among the polymer chains contributes mainly to the modulus of the MMC gels, and they are also the main reason for the presence of hysteresis in the loading-unloading cycles. PMID:24093971

Jiang, Fangzhi; Huang, Ting; He, Changcheng; Brown, Hugh R; Wang, Huiliang

2013-10-31

230

Efficacy of macromolecular crowding in forcing proteins to fold.  

PubMed

The intrinsically unstructured protein, reduced and carboxyamidated RNase T1 (TCAM) was used to determine the degree to which macromolecular crowding agents increase the equilibrium constant for folding. TCAM is not catalytically active in an aqueous assay system alone, but becomes catalytically active on addition of 400 mg/ml dextran 70. The activity observed accounts for approximately 16% of the total available TCAM in solution. We interpret this result to mean that 16% of the TCAM becomes folded protein in the presence of the 400 mg/ml dextran 70, and this translates into an approximately five-fold increase in the equilibrium constant for folding. Sarcosine-induced folding of TCAM was performed in the presence of 0, 100, 200 and 300 mg/ml dextran 70, and apparent deltaG(o)(N-D) values determined from the linear extrapolation method provide an estimated 22% folded TCAM formed in the limit of zero sarcosine concentration and in presence of 400 mg/ml dextran 70. The increase in TCAM folding equilibrium constant using this method of determination is approximately 7.5-fold. Overall, the results indicate that macromolecular crowding agents are only modestly effective in promoting folding of this intrinsically unstructured protein. PMID:12487997

Qu, Youxing; Bolen, D W

2002-12-10

231

Radial distributions of density within macromolecular complexes determined from dark-field electron micrographs  

Microsoft Academic Search

A procedure has been developed for direct determination of radial distributions of density in filamentous and spheroidal particles by analyzing dark-field scanning transmission electron micrographs of unstained freeze-dried specimens. Unlike electron microscopic methods based on staining or shadowing with heavy atoms, this approach can be used to probe the internal structure of macromolecular complexes. As an experimental proving ground, we

A. C. Steven; J. F. Hainfeld; B. L. Trus; P. M. Steinert; J. S. Wall

1984-01-01

232

Macromolecular Chemistry of Coalification: Quarterly Report for the Period May 1, 1987-July 31, 1987.  

National Technical Information Service (NTIS)

A molecular level explanation for the dilatometric behavior of an hvAb coal is sought. The macromolecular network structure of bituminous coals is described with emphasis on the non-covalent interactions responsible for coals being glasses at room tempera...

J. W. Larsen J. Kovac

1987-01-01

233

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

234

Crystal structure solution from experimentally determined atomic pair distribution functions  

SciTech Connect

An extension of the Liga algorithm for structure solution from atomic pair distribution functions (PDFs), to handle periodic crystal structures with multiple elements in the unit cell, is described. The procedure is performed in three separate steps. First, pair distances are extracted from the experimental PDF. In the second step the Liga algorithm is used to find unit-cell sites consistent with these pair distances. Finally, the atom species are assigned over the cell sites by minimizing the overlap of their empirical atomic radii. The procedure has been demonstrated on synchrotron X-ray PDF data from 16 test samples. The structure solution was successful for 14 samples, including cases with enlarged supercells. The algorithm success rate and the reasons for the failed cases are discussed, together with enhancements that should improve its convergence and usability.

Juhas, P.; Granlund, L.; Gujarathi, S.R.; Duxbury, P.M.; Billinge, S.J.L. (MSU); (Columbia)

2010-05-25

235

Empirical Magnetic Structure Solution of Frustrated Spin Systems  

NASA Astrophysics Data System (ADS)

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 structuresolution” but also reproduce the full three-dimensional magnetic scattering pattern.

Paddison, Joseph A. M.; Goodwin, Andrew L.

2012-01-01

236

Structural and spectroscopic properties of water around small hydrophobic solutes.  

PubMed

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

2012-09-27

237

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.

Montagna, Maria; Sterpone, Fabio; Guidoni, Leonardo

2013-01-01

238

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

239

Structure and rheology of associative triblocks in microemulsion solutions  

NASA Astrophysics Data System (ADS)

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) attraction, similar to that calculated by Milner and Witten for associative polymer brushes between flat plates. The attraction we calculate is weaker than that given by the Derjaguin approximation, and excluded volume moderates the attraction and softens the repulsion between spheres. The free energy was used to estimate an interparticle potential, which in turn was used to compute structure factors for solutions of associative polymers via Monte Carlo simulations. As a model system for our experiments, we have chosen PEO-PI-PEO triblocks in an AOT/water/decane microemulsion. Upon dilution with decane, the solutions phase separate into a dense, high viscosity phase and a dilute, low viscosity phase. We have performed both small-angle neutron scattering (SANS) and rheology on these solutions. Structure factors derived from our SANS data agree fairly well with those predicted by our theory and indicate that the droplets reside in an attractive minimum. The rheology of these solutions shows several interesting features that are not predicted by classical reversible network theory. Data from oscillatory experiments indicate a single relaxation time at low polymer concentrations but show evidence of a slower relaxation for higher concentrations. In addition, some solutions exhibit a maximum in the high shear viscosity. Some of our observations are predicted by the flowerlike micelle theory developed by Semenov and co-workers; however, our data is not completely consistent with the theoretical predictions. The high frequency modulus scales roughly quadratically with polymer concentration and can be correlated using a colloidal scaling proposed by Pham and co-workers.

Bhatia, Surita Rani

240

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

241

Travelling Wave Solutions in Multigroup Age-Structured Epidemic Models  

NASA Astrophysics Data System (ADS)

Age-structured epidemic models have been used to describe either the age of individuals or the age of infection of certain diseases and to determine how these characteristics affect the outcomes and consequences of epidemiological processes. Most results on age-structured epidemic models focus on the existence, uniqueness, and convergence to disease equilibria of solutions. In this paper we investigate the existence of travelling wave solutions in a deterministic age-structured model describing the circulation of a disease within a population of multigroups. Individuals of each group are able to move with a random walk which is modelled by the classical Fickian diffusion and are classified into two subclasses, susceptible and infective. A susceptible individual in a given group can be crisscross infected by direct contact with infective individuals of possibly any group. This process of transmission can depend upon the age of the disease of infected individuals. The goal of this paper is to provide sufficient conditions that ensure the existence of travelling wave solutions for the age-structured epidemic model. The case of two population groups is numerically investigated which applies to the crisscross transmission of feline immunodeficiency virus (FIV) and some sexual transmission diseases.

Ducrot, Arnaut; Magal, Pierre; Ruan, Shigui

2010-01-01

242

Macromolecular and dendrimer-based magnetic resonance contrast agents.  

PubMed

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

2010-09-01

243

Macromolecular organization of chicken type X collagen in vitro  

PubMed Central

The macromolecular structure of type X collagen in the matrices of primary cultures of chick hypertrophic chondrocytes was initially investigated using immunoelectron microscopy. Type X collagen was observed to assemble into a matlike structure with-in the matrix elaborated by hypertrophic chondrocytes. The process of self assembly was investigated at the molecular level using purified chick type X collagen and rotary-shadowing EM. It was shown that under neutral conditions at 34 degrees C, individual type X collagen molecules associate rapidly into multimeric clusters via their carboxy-terminal globular domains forming structures with a central nodule of carboxy- terminal domains and the triple helices radiating outwards. Prolonged incubation resulted in the formation of a regular hexagonal lattice by lateral association of the juxtaposed triple-helical domains from adjacent multimeric clusters. This extended lattice may play an important role in modifying the cartilage matrix for subsequent events occurring in endochondral bone formation.

1991-01-01

244

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

245

Structure formation in films of weakly charged block polyelectrolyte solutions  

NASA Astrophysics Data System (ADS)

A mean-field dynamic density functional theory is used to describe a phase diagram of concentrated solutions of weakly charged flexible block polyelectrolytes in a film. Electrostatics is taken into account by applying the local electroneutrality constraint (the Donnan membrane equilibrium approach). In the Donnan limit it is assumed that a salt added to the solution perfectly screens long-range electrostatic interactions. The phase diagram of a solution of a triblock polyelectrolyte in a film as a function of the solvent concentration and the charge of the polyelectrolyte (solvophilic) block is calculated for a given film thickness. The phase behavior of the block polyelectrolyte film arises from the interplay between surface-induced alignment and the electrostatically-driven structure formation. The observed mesoscopic structures (lamellar, perforated lamellar, cylindrical, micellar, and mixed phases) are oriented parallel to the surfaces for the considered case of morphologies unfrustrated by the film thickness. Structures with connections between parallel layers (bicontinuous, etc.) are not formed. As a result of surface-induced ordering, the region of ordered phases in a film is wider than in bulk and the phase boundary between ordered and disordered phases is more diffuse. As in the case of unconfined block polyelectrolyte solution, the solution in a film does not follow the lyotropic sequence of phases of such a block copolymer upon increase in the charge of the polyelectrolyte block. Upon changing the charge of the solvophilic copolymer block, transformations of copolymer morphology take place via change in curvature of polymeric domains. Due to confinement of a polyelectrolyte film, no swelling of solvophilic domains is observed.

Kyrylyuk, A. V.; Fraaije, J. G. E. M.

2004-11-01

246

Electronic Structures of Zirconium Hydride and Hydrogen Solid Solution  

Microsoft Academic Search

Electronic structures of zirconium hydride and hydrogen solid solution have been evaluated by the X?ray photoelec- tron spectroscopy andrst-principles molecular orbital calculation. From the valence band spectra of the solid zirconium hydride, the occurrence of the valence electron transfer from Zr 4d band to Zr?H bonding state was found to induce the reduction of Zr?Zr metallic bonds with increasing the

Takanori NISHIZAKI; Shinsuke YAMANAKA

247

Acoustic absorption and thixotropic structure in lysozyme solution  

Microsoft Academic Search

Summary  The acoustic-absorption coefficient is measured in a 1% w\\/w lysozyme solution, at frequencies ranging from 5 to 50 MHz, as\\u000a a function of time. It is shown that a relaxation process due to diffusional motion of clusters exists. Such a process is\\u000a gradually quenched, as the interacting clusters become fixed in a thixotropic solidlike structure. The obtained results are\\u000a discussed

R. Giordano; F. Mallamace; F. Wanderlingh

1983-01-01

248

Light scattering measurements supporting helical structures for chromatin in solution.  

PubMed

Laser light scattering measurements have been made on a series of polynucleosomes containing from 50 to 150 nucleosomes. Radii of gyration have been determined as a function of polynucleosome length for different ionic strength solutions. The results suggest that at low ionic strength the chromatin adopts a loosely helical structure rather than a random coil. The helix becomes more regular on increasing the ionic strength, the dimension resembling those proposed by Finch and Klug for their solenoid model. PMID:662693

Campbell, A M; Cotter, R I; Pardon, J F

1978-05-01

249

Solution structural studies of molybdate–nucleotide polyanions  

Microsoft Academic Search

The complexation of molybdate with the nucleotides adenosine-5?-monophosphate (5?-AMP), adenosine-3?-monophosphate (3?-AMP) and guanosine-5?-monophosphate (5?-GMP) has been investigated by 1H and 31P NMR and Mo K-edge X-ray absorption near edge (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopy. Acidification of aqueous solutions containing molybdate and each of the nucleotides resulted in the formation of a single species characterized by 1H

Lyndal M. R Hill; Graham N George; Anne-Kathrin Duhme-Klair; Charles G Young

2002-01-01

250

Solution structural studies of molybdate-nucleotide polyanions.  

PubMed

The complexation of molybdate with the nucleotides adenosine-5'-monophosphate (5'-AMP), adenosine-3'-monophosphate (3'-AMP) and guanosine-5'-monophosphate (5'-GMP) has been investigated by (1)H and (31)P NMR and Mo K-edge X-ray absorption near edge (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopy. Acidification of aqueous solutions containing molybdate and each of the nucleotides resulted in the formation of a single species characterized by (1)H resonances which are deshielded relative to those of free nucleotide. Analysis of the two-component systems indicated a Mo/nucleotide ratio of 2.5:1 for the complexation species. White compounds, characterized as Na(2)[Mo(5)O(15)(HB)(2)] (B=5'-AMP, 5'-GMP), have been isolated from the acidified molybdate/H(2)B solutions. Dissolution in D(2)O replicates the NMR spectra of the solution species observed prior to precipitation. Solution and solid state Mo K-edge XAS and EXAFS spectroscopy of Na(2)[Mo(5)O(15)(HAMP)(2)] and Na(6)[Mo(5)O(15)(PO(4))(2)] provide convincing evidence for the presence of a pentamolybdodiphosphate core in the molybdate-nucleotide complexes in both the solid and solution states. PMID:11897341

Hill, Lyndal M R; George, Graham N; Duhme-Klair, Anne Kathrin; Young, Charles G

2002-02-01

251

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

252

Exploring large macromolecular functional motions on clusters of multicore processors  

NASA Astrophysics Data System (ADS)

Normal modes in internal coordinates (IC) furnish an excellent way to model functional collective motions of macromolecular machines, but exhibit a high computational cost when applied to large-sized macromolecules. In this paper, we significantly extend the applicability of this approach towards much larger systems by effectively solving the computational bottleneck of these methods, the diagonalization step and associated large-scale eigenproblem, on a small cluster of nodes equipped with multicore technology. Our experiments show the superior performance of iterative Krylov-subspace methods for the solution of the dense generalized eigenproblems arising in these biological applications over more traditional direct solvers implemented on top of state-of-the-art libraries. The presented approach expedites the study of the collective conformational changes of large macromolecules opening a new window for exploring the functional motions of such relevant systems.

López-Blanco, José R.; Reyes, Ruymán; Aliaga, José I.; Badia, Rosa M.; Chacón, Pablo; Quintana-Ortí, Enrique S.

2013-08-01

253

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

254

Macromolecular extraction based on contour evolution  

NASA Astrophysics Data System (ADS)

Detecting the region of interest plays an important role in the field of image processing and analysis. For the microscopic image of plant embryo slice, region of interest usually indicates various cells or macromolecules. Combining contour evolution theory and pulse coupled neural network, we propose a new method of macromolecular detection and extraction for biological microscopic image. Some existing methods are compared with the proposed method. Experimental results show the proposed method has the better performance than existing methods.

Wang, Zhaobin; Guo, Miao; Zhu, Ying; Yang, Lizhen; Ma, Yi-de

2013-03-01

255

Macromolecular nanotheranostics for multimodal anticancer therapy  

NASA Astrophysics Data System (ADS)

Macromolecular carrier materials based on N-(2-hydroxypropyl)methacrylamide (HPMA) are prototypic and well-characterized drug delivery systems that have been extensively evaluated in the past two decades, both at the preclinical and at the clinical level. Using several different imaging agents and techniques, HPMA copolymers have been shown to circulate for prolonged periods of time, and to accumulate in tumors both effectively and selectively by means of the Enhanced Permeability and Retention (EPR) effect. Because of this, HPMA-based macromolecular nanotheranostics, i.e. formulations containing both drug and imaging agents within a single formulation, have been shown to be highly effective in inducing tumor growth inhibition in animal models. In patients, however, as essentially all other tumor-targeted nanomedicines, they are generally only able to improve the therapeutic index of the attached active agent by lowering its toxicity, and they fail to improve the efficacy of the intervention. Bearing this in mind, we have recently reasoned that because of their biocompatibility and their beneficial biodistribution, nanomedicine formulations might be highly suitable systems for combination therapies. In the present manuscript, we briefly summarize several exemplary efforts undertaken in this regard in our labs in the past couple of years, and we show that long-circulating and passively tumor-targeted macromolecular nanotheranostics can be used to improve the efficacy of radiochemotherapy and of chemotherapy combinations.

Huis in't Veld, Ruben; Storm, Gert; Hennink, Wim E.; Kiessling, Fabian; Lammers, Twan

2011-10-01

256

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

257

Macromolecular neutron crystallography at the Protein Crystallography Station (PCS)  

PubMed Central

The Protein Crystallography Station (PCS) at Los Alamos Neutron Science Center is a high-performance beamline that forms the core of a capability for neutron macromolecular structure and function determination. Neutron diffraction is a powerful technique for locating H atoms and can therefore provide unique information about how biological macro­molecules function and interact with each other and smaller molecules. Users of the PCS have access to neutron beam time, deuteration facilities, the expression of proteins and the synthesis of substrates with stable isotopes and also support for data reduction and structure analysis. The beamline exploits the pulsed nature of spallation neutrons and a large electronic detector in order to collect wavelength-resolved Laue patterns using all available neutrons in the white beam. The PCS user facility is described and highlights from the user program are presented.

Kovalevsky, Andrey; Fisher, Zoe; Johnson, Hannah; Mustyakimov, Marat; Waltman, Mary Jo; Langan, Paul

2010-01-01

258

Solution structure of murine macrophage inflammatory protein-2.  

PubMed

The solution structure of murine macrophage inflammatory protein-2 (MIP-2), a heparin-binding chemokine that is secreted in response to inflammatory stimuli, has been determined using two-dimensional homonuclear and heteronuclear NMR spectroscopy. Structure calculations were carried out by means of torsion-angle molecular dynamics using the program X-PLOR. The structure is based on a total of 2390 experimental restraints, comprising 2246 NOE-derived distance restraints, 44 distance restraints for 22 hydrogen bonds, and 100 torsion angle restraints. The structure is well-defined, with the backbone (N, Calpha, C) and heavy atom atomic rms distribution about the mean coordinates for residues 9-69 of the dimer being 0.57 +/- 0.16 A and 0.96 +/- 0.12 A, respectively. The N- and C-terminal residues (1-8 and 70-73, respectively) are disordered. The overall structure of the MIP-2 dimer is similar to that reported previously for the NMR structures of MGSA and IL-8 and consists of a six-stranded antiparallel beta-sheet (residue 25-29, 39-44, and 48-52) packed against two C-terminal antiparallel alpha-helices. A best fit superposition of the NMR structure of MIP-2 on the structures of MGSA, NAP-2, and the NMR and X-ray structures of IL-8 are 1.11, 1.02, 1.27, and 1.19 A, respectively, for the monomers, and 1.28, 1.10, 1.55, and 1.36 A, respectively, for the dimers (IL-8 residues 7-14 and 16-67, NAP-2 residues 25-84). At the tertiary level, the main differences between the MIP-2 solution structure and the IL-8, MGSA, and NAP-2 structures involve the N-terminal loop between residues 9-23 and the loops formed by residues 30-38 and residues 53-58. At the quaternary level, the difference between MIP-2 and IL-8, MGSA, or NAP-2 results from differing interhelical angles and separations. PMID:9622482

Shao, W; Jerva, L F; West, J; Lolis, E; Schweitzer, B I

1998-06-01

259

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.

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

1999-01-01

260

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.

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

2010-01-01

261

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

262

The solution structure of acyl carrier protein from Mycobacterium tuberculosis.  

PubMed

Acyl carrier protein (ACP) performs the essential function of shuttling the intermediates between the enzymes that constitute the type II fatty acid synthase system. Mycobacterium tuberculosis is unique in producing extremely long mycolic acids, and tubercular ACP, AcpM, is also unique in possessing a longer carboxyl terminus than other ACPs. We determined the solution structure of AcpM using protein NMR spectroscopy to define the similarities and differences between AcpM and the typical structures. The amino-terminal region of the structure is well defined and consists of four helices arranged in a right-handed bundle held together by interhelical hydrophobic interactions similar to the structures of other bacterial ACPs. The unique carboxyl-terminal extension from helix IV has a "melted down" feature, and the end of the molecule is a random coil. A comparison of the apo- and holo-forms of AcpM revealed that the 4'-phosphopantetheine group oscillates between two states; in one it is bound to a hydrophobic groove on the surface of AcpM, and in another it is solvent-exposed. The similarity between AcpM and other ACPs reveals the conserved structural motif that is recognized by all type II enzymes. However, the function of the coil domain extending from helix IV to the carboxyl terminus remains enigmatic, but its structural characteristics suggest that it may interact with the very long chain intermediates in mycolic acid biosynthesis or control specific protein-protein interactions. PMID:11825906

Wong, Hing C; Liu, Gaohua; Zhang, Yong-Mei; Rock, Charles O; Zheng, Jie

2002-05-01

263

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

264

The Promise of Macromolecular Crystallization in Micro-fluidic Chips  

NASA Technical Reports Server (NTRS)

Micro-fluidics, or lab on a chip technology, is proving to be a powerful, rapid, and efficient approach to a wide variety of bio-analytical and microscale bio-preparative needs. The low materials consumption, combined with the potential for packing a large number of experiments in a few cubic centimeters, makes it an attractive technique for both initial screening and subsequent optimization of macromolecular crystallization conditions. Screening operations, which require equilibrating macromolecule solution with a standard set of premixed solutions, are relatively straightforward and have been successfully demonstrated in a micro-fluidics platform. More complex optimization methods, where crystallization solutions are independently formulated from a range of stock solutions, are considerably more complex and have yet to be demonstrated. To be competitive with either approach, a micro-fluidics system must offer ease of operation, be able to maintain a sealed environment over several weeks to months, and give ready access for the observation of crystals as they are grown.

vanderWoerd, Mark; Ferree, Darren; Pusey, Marc

2003-01-01

265

Effects of Daflon 500mg on postischemic macromolecular leak syndrome in striated skin muscle of the hamster.  

PubMed

We have recently shown that the purified micronized flavonoid fraction (90% diosmin and 10% hesperidin) Daflon 500 mg attenuates reperfusion injury in the striated skin muscle of the hamster. Herein, we report on the action of Daflon 500 mg on postischemic macromolecular leakage of FITC-dextran 150 kD provoked by tourniquet ischemia. Intravital fluorescence microscopy was used for analysis of macromolecular leakage in the microcirculation model of the hamster. A tourniquet ischemia of 4 h duration was induced followed by reperfusion. Animals were treated by gavage of Daflon 500 mg (n = 6) for 8 days at a daily dose of 30 mg kg(-1) body weight. Control animals received equivalent volumes of the vehicle (5% Arabic gum solution, n = 6). Measurements of the microcirculatory parameters were made before induction of ischemia and at 0.5, 2 and 24 h of reperfusion. After induction of ischemia, macromolecular leakage from postcapillary venules was significantly enhanced in vehicle-treated animals. Treatment with Daflon 500 mg significantly attenuated macromolecular leakage of FITC-dextran 150 kD. Preliminary data from a histomorphometric analysis (n = 3/experimental group) indicated that the number of emigrated (extravascular) leukocytes after ischemia reperfusion was markedly reduced in Daflon 500 mg-treated animals as compared to controls. These data indicate that Daflon 500 mg prevents leakage of the macromolecular tracer FITC-dextran 150 kD from postcapillary venules after postischemic reperfusion, presumably through an inhibitory action on the emigration of activated leukocytes. PMID:9477038

Nolte, D; Pickelman, S; Schütze, E; Möllmann, M; Messmer, K

1997-01-01

266

The structure of the chromatin core particle in solution.  

PubMed Central

The shape and size of the nucleosomal core particle from chromatin has been examined by analysis of neutron and X-ray scattering data from dilute solutions. Calculations of scattering for many different models have been made and only one model was able to account for both the X-ray and neutron profiles. This model is an oblate structure with height about 50A and diameter 110A. The DNA is mainly confined to two annuli located at the top and bottom respectively of the core particle positioned on the outside of a compact protein core which has a height of about 40A and diameter about 73A.

Pardon, J F; Worcester, D L; Wooley, J C; Cotter, R I; Lilley, D M; Richards, R M

1977-01-01

267

Extracting trends from two decades of microgravity macromolecular crystallization history  

NASA Technical Reports Server (NTRS)

Since the 1980s hundreds of macromolecular crystal growth experiments have been performed in the reduced acceleration environment of an orbiting spacecraft. Significant enhancements in structural knowledge have resulted from X-ray diffraction of the crystals grown. Similarly, many samples have shown no improvement or degradation in comparison to those grown on the ground. A complex series of interrelated factors affect these experiments and by building a comprehensive archive of the results it was aimed to identify factors that result in success and those that result in failure. Specifically, it was found that dedicated microgravity missions increase the chance of success when compared with those where crystallization took place as a parasitic aspect of the mission. It was also found that the chance of success could not be predicted based on any discernible property of the macromolecule available to us.

Judge, Russell A.; Snell, Edward H.; van der Woerd, Mark J.

2005-01-01

268

Gorgon and Pathwalking: Macromolecular Modeling Tools for Subnanometer Resolution Density Maps  

PubMed Central

The complex interplay of proteins and other molecules, often in the form of large transitory assemblies, are critical to cellular function. Today, X-ray crystallography and electron cryo-microscopy (cryo-EM) are routinely used to image these macromolecular complexes, though often at limited resolutions. Despite the rapidly growing number of macromolecular structures, few tools exist for modeling and annotating structures in the range of 3-10Å resolution. To address this need, we have developed a number of utilities specifically targeting subnanometer resolution density maps. As part of the 2010 Cryo-EM Modeling Challenge, we demonstrated two of our latest de novo modeling tools, Pathwalking and Gorgon, as well as a tool for secondary structure identification (SSEHunter) and a new rigid-body/flexible fitting tool in Gorgon. In total, we submitted 30 structural models from ten different subnanometer resolution data sets in four of the six challenge categories. Each of our utlities produced accurate structural models and annotations across the various density maps. In the end, the utilities that we present here offer users a robust toolkit for analyzing and modeling protein structure in macromolecular assemblies at non-atomic resolutions.

Baker, Matthew L.; Baker, Mariah R.; Hryc, Corey F.; Ju, Tao; Chiu, Wah

2013-01-01

269

Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat.  

PubMed

Members of the inhibitor of apoptosis (IAP) family of proteins are able to inhibit cell death following viral infection, during development or in cell lines in vitro. All IAP proteins bear one or more baculoviral IAP repeats (BIRs). Here we describe the solution structure of the third BIR domain from the mammalian IAP homolog B (MIHB/c-IAP-1). The BIR domain has a novel fold that is stabilized by zinc tetrahedrally coordinated by one histidine and three cysteine residues. The structure consists of a series of short alpha-helices and turns with the zinc packed in an unusually hydrophobic environment created by residues that are highly conserved among all BIRs. PMID:10404221

Hinds, M G; Norton, R S; Vaux, D L; Day, C L

1999-07-01

270

Structure and dynamics of of solution polymerized polyureas  

NASA Astrophysics Data System (ADS)

Polyureas consisting of alternating soft and hard (urea containing) segments exhibit physical properties that are closely related to their microphase separated structure, which consist of rigid (high Tg and sometimes crystalline) hard domains embedded in a matrix dominated by flexible polyether segments. Polyurea properties can be controlled over a rather broad range by varying the chemical structures, molecular weight of the components, and reaction stoichiometry. In the present study, we focus primarily on linear polyureas synthesized using methylene diphenyl diisocyanate and polytetramethylene oxide-di-p-aminobenzoate using a solution polymerization method. Soft segment (diamine) molecular weights were varied from 460 to 860 to 1200 g/mol and characterize their morphology, hydrogen bonding, mechanical behavior and dielectric properties upon varying molecular weight of diamines. This presentation will focus on our latest findings, particularly details of the microphase separated morphology and molecular dynamics as measured using dielectric relaxation spectroscopy

Choi, Taeyi; Jeong, Youmi; Runt, James

2011-03-01

271

Interfacial structures of acidic and basic aqueous solutions  

SciTech Connect

Phase-sensitive sum-frequency vibrational spectroscopy was used to study water/vapor interfaces of HCl, HI, and NaOH solutions. The measured imaginary part of the surface spectral responses provided direct characterization of OH stretch vibrations and information about net polar orientations of water species contributing to different regions of the spectrum. We found clear evidence that hydronium ions prefer to emerge at interfaces. Their OH stretches contribute to the 'ice-like' band in the spectrum. Their charges create a positive surface field that tends to reorient water molecules more loosely bonded to the topmost water layer with oxygen toward the interface, and thus enhances significantly the 'liquid-like' band in the spectrum. Iodine ions in solution also like to appear at the interface and alter the positive surface field by forming a narrow double-charge layer with hydronium ions. In NaOH solution, the observed weak change of the 'liquid-like' band and disappearance of the 'ice-like' band in the spectrum indicates that OH{sup -} ions must also have excess at the interface. How they are incorporated in the interfacial water structure is however not clear.

Tian, C.; Ji, N.; Waychunas, G.; Shen, Y.R.

2008-10-20

272

Band-gap nonlinearity in perovskite structured solid solutions  

NASA Astrophysics Data System (ADS)

Compositional effects on optical band-gap energy using end members of ABO3 perovskites have been investigated through an optical absorption with a UV-spectroscopy. Three examples are selected, namely, BaTiO3-CaTiO3, BaTiO3-BaZrO3, and SrTiO3-BaZrO3 solid solutions. To understand the role of high temperature phase equilibria on the band-gap compositional trends, structural and microscopy data were determined. In simple systems such as Si-Ge, the nonlinear variations in band gap with composition is usually associated with the effect of the local lattice relaxations and provides a parabolic dependence, often referred to as the ``bowing'' phenomena. In the case of perovskite solutions, the cases are more complex, and a modified Vegard's law is introduced to account for the trends. This has to be considered in relation to high temperature phase formation where incomplete solid solutions and two-phase regions exist. In addition to high temperature phases, low temperature displacive phase transitions and complex nonstoichiometry also perturb the band-gap variation in perovskite oxide materials.

Lee, Soonil; Levi, Roni D.; Qu, Weiguo; Lee, Sung Chan; Randall, Clive A.

2010-01-01

273

Development of macromolecular prodrug for rheumatoid arthritis?  

PubMed Central

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is considered to be one of the major public health problems worldwide. The development of therapies that target tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6) and co-stimulatory pathways that regulate the immune system have revolutionized the care of patients with RA. Despite these advances, many patients continue to experience symptomatic and functional impairment. To address this issue, more recent therapies that have been developed are designed to target intracellular signaling pathways involved in immunoregulation. Though this approach has been encouraging, there have been major challenges with respect to off-target organ side effects and systemic toxicities related to the widespread distribution of these signaling pathways in multiple cell types and tissues. These limitations have led to an increasing interest in the development of strategies for the macromolecularization of anti-rheumatic drugs, which could target them to the inflamed joints. This approach enhances the efficacy of the therapeutic agent with respect to synovial inflammation, while markedly reducing non-target organ adverse side effects. In this manuscript, we provide a comprehensive overview of the rational design and optimization of macromolecular prodrugs for treatment of RA. The superior and the sustained efficacy of the prodrug may be partially attributed to their Extravasation through Leaky Vasculature and subsequent Inflammatory cell-mediated Sequestration (ELVIS) in the arthritic joints. This biologic process provides a plausible mechanism, by which macromolecular prodrugs preferentially target arthritic joints and illustrates the potential benefits of applying this therapeutic strategy to the treatment of other inflammatory diseases.

Yuan, Fang; Quan, Ling-dong; Cui, Liao; Goldring, Steven R.; Wang, Dong

2012-01-01

274

Growth and structure of zirconium hydrous polymers in aqueous solutions  

SciTech Connect

Zirconium oxychloride solutions prepared at different pH were heated at elevated temperatures for various aging periods to gain an understanding of the growth mechanism and structure of zirconium hydrous polymers. Small angle X-ray scattering (SAXS) measurements were made on these solutions. It was observed that shape of clusters at the earlier stages of growth is close to a rod rather than a sheet as suggested earlier. The scattering data indicate that a rod-shaped primary particle is formed at pH 1.2, and on an increase in the pH, the primary particles become more branched. On aging more than 1,250 min at 92 C, these primary particles form large aggregates while retaining the primary particle structure. These aggregates, which are mass fractal in nature, restructure while growing in size and eventually transform into dense particles. Scattering data in this study were not enough to determine a specific kinetic growth model of the aggregates because the scattering intensity at low q constantly changes with time during the restructuring process.

Singhal, A. [Oak Ridge National Lab., TN (United States)] [Oak Ridge National Lab., TN (United States); [Univ. of Tennessee, Knoxville, TN (United States). Dept. of Chemistry; Toth, L.M.; Lin, J.S. [Oak Ridge National Lab., TN (United States)] [Oak Ridge National Lab., TN (United States); Beaucage, G. [Univ. of Cincinnati, OH (United States). Dept. of Materials Science and Engineering] [Univ. of Cincinnati, OH (United States). Dept. of Materials Science and Engineering; Peterson, J. [Univ. of Tennessee, Knoxville, TN (United States). Dept. of Chemistry] [Univ. of Tennessee, Knoxville, TN (United States). Dept. of Chemistry

1997-10-15

275

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

276

The solution structure of apo-iron regulatory protein 1.  

PubMed

Iron is a cofactor for many proteins that are involved in essential metabolic processes. However, iron must be strictly regulated because it can react with oxygen to generate cytotoxic reactive oxygen intermediates. Iron regulatory protein 1 (IRP1) is a bi-functional protein that can act either as a post-transcriptional regulator of mRNAs containing iron responsive elements, or as a [4Fe-4S] cluster-containing cytosolic aconitase. Previous X-ray crystallography results show that IRP1 is in an open L-shape conformation when bound to IRE-RNAs, and in a globular conformation when it binds an iron-sulfur cluster. The structure of apo-IRP1 and the mechanism by which it transforms to either functional state is unknown. Therefore, small angle X-ray scattering was used to determine the low resolution solution structure of apo-IRP1 and to characterize its biophysical properties. These results show that apo-IRP1 has a radius of gyration (Rg) of 33.6±0.3Å, and a Dmax of 118±2Å. The ab initio and rigid-body modeling results show that apo-IRP1 is in an open conformation in solution, and the ensemble optimization results show that the molecules stay narrowly distributed about a Rg of 33-34Å. The open apo-IRP1 conformation seems optimal for subsequent conversion to either functional end state: RNA-binding, or cytosolic aconitase. PMID:23590984

Shand, O'Neil; Volz, Karl

2013-07-25

277

Automated macromolecular crystal detection system and method  

DOEpatents

An automated macromolecular method and system for detecting crystals in two-dimensional images, such as light microscopy images obtained from an array of crystallization screens. Edges are detected from the images by identifying local maxima of a phase congruency-based function associated with each image. The detected edges are segmented into discrete line segments, which are subsequently geometrically evaluated with respect to each other to identify any crystal-like qualities such as, for example, parallel lines, facing each other, similarity in length, and relative proximity. And from the evaluation a determination is made as to whether crystals are present in each image.

Christian, Allen T. (Tracy, CA); Segelke, Brent (San Ramon, CA); Rupp, Bernard (Livermore, CA); Toppani, Dominique (Fontainebleau, FR)

2007-06-05

278

Efficient sequential recovery of nucleolar macromolecular components  

PubMed Central

Efficient extraction and accurate quantification of nucleolar macromolecules are critical for in vitro analysis, especially for studying RNA, DNA, and protein dynamics under identical conditions. There is presently no single method that efficiently and simultaneously isolates these three macromolecular constituents from purified nucleoli. We have developed an optimized method, which without evident loss, extracts, and solubilizes protein recovered from a single sample following TRIzol isolation of RNA and DNA. The solubilized protein can be accurately quantified by protein bicinchoninic acid assay and assessed by polyacrylamide gel electrophoresis. We have successfully applied this approach to extract and quantify all three nucleolar components, and to study nucleolar protein responses after actinomycin D treatment.

Bai, Baoyan; Laiho, Marikki

2013-01-01

279

Efficient sequential recovery of nucleolar macromolecular components.  

PubMed

Efficient extraction and accurate quantification of nucleolar macromolecules are critical for in vitro analysis, especially for studying RNA, DNA, and protein dynamics under identical conditions. There is presently no single method that efficiently and simultaneously isolates these three macromolecular constituents from purified nucleoli. We have developed an optimized method, which without evident loss, extracts, and solubilizes protein recovered from a single sample following TRIzol isolation of RNA and DNA. The solubilized protein can be accurately quantified by protein bicinchoninic acid assay and assessed by polyacrylamide gel electrophoresis. We have successfully applied this approach to extract and quantify all three nucleolar components, and to study nucleolar protein responses after actinomycin D treatment. PMID:22890538

Bai, Baoyan; Laiho, Marikki

2012-10-01

280

Structure of polyurethane spinning solutions and its effect on properties of spandex fibre  

Microsoft Academic Search

The supermolecular structure of solutions of polyurethane and of polytetramethylene ether glycol has been studied. It has been found that spinning solutions having a large content of gel-particles are obtained from a more “structurized” polytetramethylene ether glycol.

L. V. Prozorov; O. A. Ponomareva

1989-01-01

281

Solution structure of Ca2+-free rat ?-parvalbumin (oncomodulin)  

PubMed Central

Relative to other parvalbumin isoforms, the mammalian ?-parvalbumin (oncomodulin) displays attenuated divalent ion affinity. High-resolution structural data for the Ca2+-bound protein have provided little insight into the physical basis for this behavior, prompting an examination of the unliganded state. This article describes the solution structure and peptide backbone dynamics of Ca2+-free rat ?-parvalbumin (?-PV). Ca2+ removal evidently provokes significant structural alterations. Interaction between the D helix and the AB domain in the Ca2+-bound protein is greatly diminished in the apo-form, permitting the D helix to straighten. There is also a significant reorganization of the hydrophobic core and a concomitant remodeling of the interface between the AB and CD-EF domains. These modifications perturb the orientation of the C and D helices, and the energetic penalty associated with their reversal could contribute to the low-affinity signature of the CD site. By contrast, Ca2+ removal causes a comparatively minor perturbation of the E and F helices, consistent with the more typical divalent ion affinity observed for the EF site. Ca2+-free rat ?-PV retains structural rigidity on the picosecond–nanosecond timescale. At 20°C, the majority of amide vectors show no evidence for motion on timescales above 20 ps, and the average order parameter for the entire molecule is 0.92.

Henzl, Michael T.; Tanner, John J.

2007-01-01

282

Direct structure analysis of a paraffin solid solution.  

PubMed Central

Single microcrystals of a 1:1 solid solution of n-C32H66/n-C36H74 have been grown by epitaxial nucleation on benzoic acid, and 0kl electron diffraction patterns from them can be obtained with a lamellar spacing characteristic of the intermediate n-paraffin n-C34H70. This average structure is also indicated by indices (space group Pca21) for major intensities in this zone. Direct phasing of the intensity data is carried out by combined use of low-dose electron microscope lattice images (to assign values to the "lamellar" reflections) and three-phase structure invariant relationships (to find values for the "polyethylene" reflections). The computed electrostatic potential map closely resembles the crystal structure of n-C34H74, for which all 34 atom positions can be found. It is apparent, however, that lower atomic occupancies at the chain ends correspond to anticipated disorder at the lamellar interface. Structural refinement based on this occupancy results in a good match to the observed intensity data. Images

Dorset, D L

1990-01-01

283

Solution structure and stability of tryptophan-containing nucleopeptide duplexes.  

PubMed

Covalently linked peptide-oligonucleotide hybrids were used as models for studying tryptophan-DNA interactions. The structure and stability of several hybrids in which peptides and oligonucleotides are linked through a phosphodiester bond between the hydroxy group of a homoserine (Hse) side chain and the 3'-end of the oligonucleotide, have been studied by both NMR and CD spectroscopy and by restrained molecular dynamics methods. The three-dimensional solution structure of the complex between Ac-Lys-Trp-Lys-Hse(p3'dGCATCG)-Ala-OH (p=phosphate, Ac=acetyl) and its complementary strand 5'dCGTAGC has been determined from a set of 276 experimental NOE distances and 33 dihedral angle constraints. The oligonucleotide structure is a well-defined duplex that belongs to the B-form family of DNA structures. The covalently linked peptide adopts a folded structure in which the tryptophan side chain stacks against the 3'-terminal guanine moiety, which forms a cap at the end of the duplex. This stacking interaction, which resembles other tryptophan-nucleobase interactions observed in some protein-DNA complexes, is not observed in the single-stranded form of Ac-Lys-Trp-Lys-Hse(p3'dGCATCG)-Ala-OH, where the peptide chain is completely disordered. A comparison with the pure DNA duplex, d(5'GCTACG3')-(5'CGTAGC3'), indicates that the interaction between the peptide and the DNA contributes to the stability of the nucleopeptide duplex. The different contributions that stabilize this complex have been evaluated by studying other nucleopeptide compounds with related sequences. PMID:12512075

Gómez-Pinto, Irene; Marchán, Vicente; Gago, Federico; Grandas, Anna; González, Carlos

2003-01-01

284

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

285

Solution structure of beta(2)-microglobulin and insights into fibrillogenesis.  

PubMed

The solution structure of human beta(2)-microglobulin (beta(2)-m) was determined by (1)H NMR spectroscopy and restrained modeling calculations. Compared to the crystal structure of type I major histocompatibility complex (MHC-I), where the protein is associated to the heavy-chain component, several differences are observed, i.e., increased separation between strands A and B, displacements of strand C' and loop DE, shortening of strands D and E. These modifications can be considered as the prodromes of the amyloid transition. Even minor charge changes in response to pH, as is the case with H31 imidazole protonation, trigger the transition that starts with unpairing of strand A. The same mechanism accounts for the partial unfolding and fiber formation subsequent to Cu(2+) binding which is shown to occur primarily at H31. Solvation of the protected regions in MHC-I decreases the tertiary packing by breaking the contiguity of the surface hydrophobic patches via surface charge cluster. Mutants or truncated forms of beta(2)-m can be designed to remove the instability from H31 titration or to enhance the instability through surface charge suppression. By monitoring the conformational evolution of wild-type protein and variants thereof, either in response or absence of external perturbation, valuable insights into intermediate structure and fibrillogenesis mechanisms are gained. PMID:16081329

Esposito, Gennaro; Corazza, Alessandra; Viglino, Paolo; Verdone, Giuliana; Pettirossi, Fabio; Fogolari, Federico; Makek, Ads; Giorgetti, Sofia; Mangione, Palma; Stoppini, Monica; Bellotti, Vittorio

2005-11-10

286

Structure and dynamics of aqueous solution of uranyl ions  

NASA Astrophysics Data System (ADS)

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; Choudhury, Niharendu

2014-04-01

287

Macromolecular crowding induces a molten globule state in the C-terminal domain of histone H1.  

PubMed

We studied the secondary structure of the C-terminal domains of the histone H1 subtypes H1 degrees (C-H1 degrees ) and H1t (C-H1t) in the presence of macromolecular crowding agents (Ficoll 70 and PEG 6000) by IR spectroscopy. The carboxyl-terminal domain has little structure in aqueous solution but became extensively folded in the presence of crowding agents. In 30% PEG, C-H1 degrees contained 19% alpha-helix, 28% beta-sheet, 16% turns, and 31% open loops. Similar proportions were observed in 30% Ficoll 70 and for C-H1t in both crowding agents. The proportions of secondary structure motifs were comparable to those of the DNA-bound domain. Kratky plots of the small-angle x-ray scattering showed that in crowding agents the C-terminus had the compaction of a globular state. Progressive dissipation of the secondary structure and a linear increase in partial heat capacity with temperature together with increased binding of ANS indicated that the C-terminus is not cooperatively folded in crowded conditions. Native-like secondary structure and compactness in absence of folding cooperativity indicate that the C-terminus in crowding agents is in a molten globule state. Folding of the C-terminus in crowded conditions may increase the rate of the transition toward the DNA-bound state and facilitate H1 diffusion inside cell nuclei. PMID:17513371

Roque, Alicia; Ponte, Inma; Suau, Pedro

2007-09-15

288

From "Simple" DNA-Protein Interactions to the Macromolecular Machines of Gene Expression  

PubMed Central

The physicochemical concepts that underlie our present ideas on the structure and assembly of the “macromolecular machines of gene expression” are developed, starting with the structure and folding of the individual protein and DNA components, the thermodynamics and kinetics of their conformational rearrangements during complex assembly, and the molecular basis of the sequence specificity and recognition interactions of the final assemblies that include the DNA genome. The role of diffusion in reduced dimensions in the kinetics of the assembly of macromolecular machines from their components is also considered, and diffusion-driven reactions are compared with those fueled by ATP binding and hydrolysis, as well as by the specific covalent chemical modifications involved in rearranging chromatin and modifying signal transduction networks in higher organisms.

von Hippel, Peter H.

2008-01-01

289

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

290

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

291

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

292

Rheological Properties and Structure of Aqueous Solutions of Polysaccharides. Solutions of Sodium Carboxymethylcellulose Fractions of Different Molar Mass  

Microsoft Academic Search

Rheological and spectrophotometric data are obtained that confirm the difference in the conformational state of Na-CMC macromolecules with a degree of polymerization of 120, 916, and 1740 in aqueous solution. It was found that the nonlinearity of the concentration curves of both the structural characteristics and the flow activation parameters is a distinctive feature of the solutions of the fraction

S. M. Prusova; I. V. Ryabinina; A. N. Prusov

2002-01-01

293

Rheological Properties and Structure of Aqueous Solutions of Polysaccharides. Solutions of Mixtures of Sodium Carboxymethylcellulose Fractions of Different Molar Mass  

Microsoft Academic Search

Rigorous relations are proposed for calculating the additive values of activation parameters of viscous flow of solutions of polymer mixtures. The point of view that the cause of deviation of the viscosity of solutions of Na-CMC fractions of the same chemical composition but significantly different molar mass from the additive values is the formation of a supermolecular structure common to

A. N. Prusov; S. M. Prusova; I. V. Ryabinina

2003-01-01

294

Hierarchical Order Parameters for Macromolecular Assembly Simulations I: Construction and Dynamical Properties of Order Parameters.  

PubMed

Macromolecular assemblies often display a hierarchical organization of macromolecules or their sub-assemblies. To model this, we have formulated a space warping method that enables capturing overall macromolecular structure and dynamics via a set of coarse-grained order parameters (OPs). This article is the first of two describing the construction and computational implementation of an additional class of OPs that has built into them the hierarchical architecture of macromolecular assemblies. To accomplish this, first, the system is divided into subsystems, each of which is described via a representative set of OPs. Then, a global set of variables is constructed from these subsystem-centered OPs to capture overall system organization. Dynamical properties of the resulting OPs are compared to those of our previous nonhierarchical ones, and implied conceptual and computational advantages are discussed for a 100ns, 2 million atom solvated Human Papillomavirus-like particle simulation. In the second article, the hierarchical OPs are shown to enable a multiscale analysis that starts with the N-atom Liouville equation and yields rigorous Langevin equations of stochastic OP dynamics. The latter is demonstrated via a force-field based simulation algorithm that probes key structural transition pathways, simultaneously accounting for all-atom details and overall structure. PMID:22661911

Singharoy, Abhishek; Sereda, Yuriy; Ortoleva, Peter J

2012-04-10

295

Hierarchical Order Parameters for Macromolecular Assembly Simulations I: Construction and Dynamical Properties of Order Parameters  

PubMed Central

Macromolecular assemblies often display a hierarchical organization of macromolecules or their sub-assemblies. To model this, we have formulated a space warping method that enables capturing overall macromolecular structure and dynamics via a set of coarse-grained order parameters (OPs). This article is the first of two describing the construction and computational implementation of an additional class of OPs that has built into them the hierarchical architecture of macromolecular assemblies. To accomplish this, first, the system is divided into subsystems, each of which is described via a representative set of OPs. Then, a global set of variables is constructed from these subsystem-centered OPs to capture overall system organization. Dynamical properties of the resulting OPs are compared to those of our previous nonhierarchical ones, and implied conceptual and computational advantages are discussed for a 100ns, 2 million atom solvated Human Papillomavirus-like particle simulation. In the second article, the hierarchical OPs are shown to enable a multiscale analysis that starts with the N-atom Liouville equation and yields rigorous Langevin equations of stochastic OP dynamics. The latter is demonstrated via a force-field based simulation algorithm that probes key structural transition pathways, simultaneously accounting for all-atom details and overall structure.

Singharoy, Abhishek; Sereda, Yuriy

2012-01-01

296

Yeast cox17 solution structure and Copper(I) binding.  

PubMed

Cox17 is a 69-residue cysteine-rich, copper-binding protein that has been implicated in the delivery of copper to the Cu(A) and Cu(B) centers of cytochrome c oxidase via the copper-binding proteins Sco1 and Cox11, respectively. According to isothermal titration calorimetry experiments, fully reduced Cox17 binds one Cu(I) ion with a K(a) of (6.15 +/- 5.83) x 10(6) M(-1). The solution structures of both apo and Cu(I)-loaded Cox17 reveal two alpha helices preceded by an extensive, unstructured N-terminal region. This region is reminiscent of intrinsically unfolded proteins. The two structures are very similar overall with residues in the copper-binding region becoming more ordered in Cu(I)-loaded Cox17. Based on the NMR data, the Cu(I) ion has been modeled as two-coordinate with ligation by conserved residues Cys(23) and Cys(26). This site is similar to those observed for the Atx1 family of copper chaperones and is consistent with reported mutagenesis studies. A number of conserved, positively charged residues may interact with complementary surfaces on Sco1 and Cox11, facilitating docking and copper transfer. Taken together, these data suggest that Cox17 is not only well suited to a copper chaperone function but is specifically designed to interact with two different target proteins. PMID:15465825

Abajian, Carnie; Yatsunyk, Liliya A; Ramirez, Benjamin E; Rosenzweig, Amy C

2004-12-17

297

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

298

Structure and dynamics of concentrated hydrochloric acid solutions.  

PubMed

Self-consistent iterative multistate empirical valence bond (SCI-MS-EVB) simulations for four different concentrated hydrochloric acid (HCl) concentrations (0.43, 0.85, 1.68, and 3.26 M) were conducted to study the structure and dynamic properties of the aqueous multiple excess proton systems. The present, more extensive simulations, confirm that the hydrated excess protons have a tendency to form metastable contact ion pairs by positioning the hydronium oxygen lone pair sides toward one another, in agreement with earlier work [ Wang, F. Izvekov, S. Voth, G. A. J. Am. Chem. Soc. 2008 , 130 , 3120 ]. This unusual behavior results from the special "amphiphilic" nature of the hydrated excess proton. Increasing the acid concentration to 3.26 M was found to have minor effects on the solvation structures of the hydrated proton and chloride counterion, while the average lifetime of the hydrated proton contact ion pairs was reduced. The addition of salts (KCl and NaCl) into the acid solution increases the stability of the hydrated proton pairs and reduces the proton diffusion. PMID:20593833

Xu, Jianqing; Izvekov, Sergei; Voth, Gregory A

2010-07-29

299

Fast macromolecular proton fraction mapping from a single off-resonance magnetization transfer measurement.  

PubMed

A new method was developed for fast quantitative mapping of the macromolecular proton fraction defined within the two-pool model of magnetization transfer. The method utilizes a single image with off-resonance saturation, a reference image for data normalization, and T(1), B(0), and B(1) maps with the total acquisition time ~10 min for whole-brain imaging. Macromolecular proton fraction maps are reconstructed by iterative solution of the matrix pulsed magnetization transfer equation with constrained values of other model parameters. Theoretical error model describing the variance due to noise and the bias due to deviations of constrained parameters from their actual values was formulated based on error propagation rules. The method was validated by comparison with the conventional multiparameter multipoint fit of the pulsed magnetization transfer model based on data from two healthy subjects and two multiple sclerosis patients. It was demonstrated theoretically and experimentally that accuracy of the method depends on the offset frequency and flip angle of the saturation pulse, and optimal ranges of these parameters are 4-7 kHz and 600°-900°, respectively. At optimal sampling conditions, the single-point method enables <10% relative macromolecular proton fraction errors. Comparison with the multiparameter fitting method revealed very good agreement with no significant bias and limits of agreement around ± 0.7%. PMID:22190042

Yarnykh, Vasily L

2012-07-01

300

Thiomers: promising platform for macromolecular drug delivery.  

PubMed

The application of macromolecules as therapeutic agents holds great promise for several major disorders such as cancer and cardiovascular disease. However, their use is limited by the lack of efficient, safe and specific delivery strategies. A promising strategy to overcome these challenges might be the use of thiolated polymers or designated thiomers. Thiomers are synthesized by immobilization of sulfhydryl bearing ligands on a polymeric backbone of well-established polymers. These multifunctional polymeric excipients show advantages in mucoadhesion, enzyme and efflux pump inhibition in comparison to unmodified polymers. One obstacle in the use of thiomers is that they are prone to oxidation at lower pH but this could be solved by introducing a completely new generation of thiomers, namely, the preactivated thiomer generation. Preactivated thiomers are mixed disulfides, which exhibit oxidation resistance and, beyond that, improved thiomer features. This review summarizes recent findings of polymeric excipients for macromolecular drug delivery as well as their synthesis and distinctive features. PMID:23190108

Laffleur, Flavia; Bernkop-Schnürch, Andreas

2012-11-01

301

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

302

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

303

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.

Garman, Elspeth F.

2010-01-01

304

Development of an online UV-visible microspectrophotometer for a macromolecular crystallography beamline  

PubMed Central

Measurement of the UV–visible absorption spectrum is a convenient technique for detecting chemical changes of proteins, and it is therefore useful to combine spectroscopy and diffraction studies. An online microspectrophotometer for the UV–visible region was developed and installed on the macromolecular crystallography beamline, BL38B1, at SPring-8. This spectrophotometer is equipped with a difference dispersive double monochromator, a mercury–xenon lamp as the light source, and a photomultiplier as the detector. The optical path is mostly constructed using mirrors, in order to obtain high brightness in the UV region, and the confocal optics are assembled using a cross-slit diaphragm like an iris to eliminate stray light. This system can measure optical densities up to a maximum of 4.0. To study the effect of radiation damage, preliminary measurements of glucose isomerase and thaumatin crystals were conducted in the UV region. Spectral changes dependent on X-ray dose were observed at around 280?nm, suggesting that structural changes involving Trp or Tyr residues occurred in the protein crystal. In the case of the thaumatin crystal, a broad peak around 400?nm was also generated after X-ray irradiation, suggesting the cleavage of a disulfide bond. Dose-dependent spectral changes were also observed in cryo-solutions alone, and these changes differed with the composition of the cryo-solution. These responses in the UV region are informative regarding the state of the sample; consequently, this device might be useful for X-ray crystallography.

Shimizu, Nobutaka; Shimizu, Tetsuya; Baba, Seiki; Hasegawa, Kazuya; Yamamoto, Masaki; Kumasaka, Takashi

2013-01-01

305

Development of an online UV-visible microspectrophotometer for a macromolecular crystallography beamline.  

PubMed

Measurement of the UV-visible absorption spectrum is a convenient technique for detecting chemical changes of proteins, and it is therefore useful to combine spectroscopy and diffraction studies. An online microspectrophotometer for the UV-visible region was developed and installed on the macromolecular crystallography beamline, BL38B1, at SPring-8. This spectrophotometer is equipped with a difference dispersive double monochromator, a mercury-xenon lamp as the light source, and a photomultiplier as the detector. The optical path is mostly constructed using mirrors, in order to obtain high brightness in the UV region, and the confocal optics are assembled using a cross-slit diaphragm like an iris to eliminate stray light. This system can measure optical densities up to a maximum of 4.0. To study the effect of radiation damage, preliminary measurements of glucose isomerase and thaumatin crystals were conducted in the UV region. Spectral changes dependent on X-ray dose were observed at around 280 nm, suggesting that structural changes involving Trp or Tyr residues occurred in the protein crystal. In the case of the thaumatin crystal, a broad peak around 400 nm was also generated after X-ray irradiation, suggesting the cleavage of a disulfide bond. Dose-dependent spectral changes were also observed in cryo-solutions alone, and these changes differed with the composition of the cryo-solution. These responses in the UV region are informative regarding the state of the sample; consequently, this device might be useful for X-ray crystallography. PMID:24121346

Shimizu, Nobutaka; Shimizu, Tetsuya; Baba, Seiki; Hasegawa, Kazuya; Yamamoto, Masaki; Kumasaka, Takashi

2013-11-01

306

Space warping order parameters and symmetry: application to multiscale simulation of macromolecular assemblies.  

PubMed

Coarse-grained features of macromolecular assemblies are understood via a set of order parameters (OPs) constructed in terms of their all-atom configuration. OPs are shown to be slowly changing in time and capture the large-scale spatial features of macromolecular assemblies. The relationship of these variables to the classic notion of OPs based on symmetry breaking phase transitions is discussed. OPs based on space warping transformations are analyzed in detail as they naturally provide a connection between overall structure of an assembly and all-atom configuration. These OPs serve as the basis of a multiscale analysis that yields Langevin equations for OP dynamics. In this context, the characteristics of OPs and PCA modes are compared. The OPs enable efficient all-atom multiscale simulations of the dynamics of macromolecular assemblies in response to changes in microenvironmental conditions, as demonstrated on the structural transitions of cowpea chlorotic mottle virus capsid (CCMV) and RNA of the satellite tobacco mosaic virus (STMV). PMID:22356532

Singharoy, Abhishek; Joshi, Harshad; Miao, Yinglong; Ortoleva, Peter J

2012-07-26

307

Water structure, dynamics, and vibrational spectroscopy in sodium bromide solutions  

NASA Astrophysics Data System (ADS)

We study theoretically the steady-state and ultrafast vibrational spectroscopy, in the OD-stretch region, of dilute HOD in aqueous solutions of sodium bromide. Based on electronic-structure calculations on clusters containing salt ions and water, we develop new spectroscopic maps that enable us to undertake this study. We calculate OD-stretch absorption line shapes as a function of salt concentration, finding good agreement with experiment. We provide molecular-level understandings of the monotonic (as a function of concentration) blueshift, and nonmonotonic line width. We also calculate the frequency time-correlation function, as measured by spectral diffusion experiments. Here again we obtain good agreement with experiment, finding that at the highest salt concentration spectral diffusion slows down by a factor of 3 or 4 (compared to pure water). For longer times than can be accessed experimentally, we find that spectral diffusion is very complicated, with processes occurring on multiple time scales. We argue that from 6 to 40 ps, relaxation involves anionic solvation shell rearrangements. Finally, we consider our findings within the general context of the Hofmeister series, concluding that this series must reflect only local ordering of water molecules.

Lin, Y.-S.; Auer, B. M.; Skinner, J. L.

2009-10-01

308

Flow structure of aqueous solutions of polyethylene oxide in the inlet region of short capillaries  

Microsoft Academic Search

The article presents data on the visualization of the flow of aqueous solution of polyethylene oxide (PEO) in the inlet ection of a capillary. The times of structural relaxation in solutions of PEO are evaluated.

Yu. F. Ivanyuta; N. V. Naumchuk; V. G. Pogrebnyak; S. V. Tverdokhleb

1985-01-01

309

Three Biomedical Beamlines at NSLS-II for Macromolecular Crystallography and Small-Angle Scattering  

NASA Astrophysics Data System (ADS)

We report on the status of the development of three beamlines for the National Synchrotron Light Source-II (NSLS-II), two for macromolecular crystallography (MX), and one for wide- and small-angle x-ray scattering (SAXS). Funded by the National Institutes of Health, this suite of Advanced Beamlines for Biological Investigations with X-rays (ABBIX) is scheduled to begin operation by 2015. The two MX beamlines share a sector with identical canted in-vacuum undulators (IVU21). The microfocusing FMX beamline on the inboard branch employs a two-stage horizontal source demagnification scheme, will cover an energy range of 5 - 23 keV, and at 12.7 keV will focus a flux of up to 1013 ph/s into a spot of 1 ?m width. The companion AMX beamline on the short outboard branch of the sector is tunable in the range of 5 - 18 keV and has a native focus of 4 ?m (h) × 2 ?m (v). This robust beamline will be highly automated, have high throughput capabilities, and with larger beams and low divergence will be well suited for structure determinations on large complexes. The high brightness SAXS beamline, LIX, will provide multiple dynamic and static experimental systems to support scientific programs in solution scattering, membrane structure determination, and tissue imaging. It will occupy a different sector, equipped with a single in-vacuum undulator (IVU23). It can produce beams as small as 1 ?m across, and with a broad energy range of 2.1 - 18 keV it will support anomalous SAXS.

Schneider, D. K.; Berman, L. E.; Chubar, O.; Hendrickson, W. A.; Hulbert, S. L.; Lucas, M.; Sweet, R. M.; Yang, L.

2013-03-01

310

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

311

Study of the Structure of Aqueous Solutions of Ionic Macromolecules by Low-Frequency Raman Spectroscopy  

Microsoft Academic Search

Using low-frequency Raman spectroscopy, the structure of aqueous solutions of polyacrylic acid as a function of polyelectrolyte concentration and chain length was studied. The fractal dimension of structures in aqueous solutions of polyacrylic acid with different acid concentrations and polyion chain lengths was determined. The size of fractal regions in systems with different structures was estimated.

A. Z. Bol'Shagina; A. M. Saletskii; A. V. Chervyakov

2001-01-01

312

Macromolecular Diffusion in Self-Assembling Biodegradable Thermosensitive Hydrogels.  

PubMed

Hydrogel formation triggered by a change in temperature is an attractive mechanism for in situ gelling biomaterials for pharmaceutical applications such as the delivery of therapeutic proteins. In this study, hydrogels were prepared from ABA triblock polymers having thermosensitive poly(N-(2-hydroxypropyl) methacrylamide lactate) flanking A-blocks and hydrophilic poly(ethylene glycol) B-blocks. Polymers with fixed length A blocks (~22 kDA) but differing PEG-midblock lengths (2, 4 and 10 kDa) were synthesized and dissolved in water with dilute fluorescein isothiocyanate (FITC)-labeled dextrans (70 and 500 kDA). Hydrogels encapsulating the dextrans were formed by raising the temperature. Fluorescence recovery after photobleaching (FRAP) studies showed that diffusion coefficients and mobile fractions of the dextran dyes decreased upon elevating temperatures above 25 °C. Confocal laser scanning microscopy and cryo-SEM demonstrated that hydrogel structure depended on PEG block length. Phase separation into polymer-rich and water-rich domains occurred to a larger extent for polymers with small PEG blocks compared to polymers with a larger PEG block. By changing the PEG block length and thereby the hydrogel structure, mobility of FITC-dextran could be tailored. At physiological pH the hydrogels degraded over time by ester hydrolysis, resulting in increased mobility of the encapsulated dye. Since diffusion can be controlled according to polymer design and concentration, plus temperature, these biocompatible hydrogels are attractive as potential in situ gelling biodegradable materials for macromolecular drug delivery. PMID:20885989

Vermonden, Tina; Jena, Sidhartha S; Barriet, David; Censi, Roberta; van der Gucht, Jasper; Hennink, Wim E; Siegel, Ronald A

2010-01-26

313

Enhancement of microwave-assisted covalent immobilization of penicillin acylase using macromolecular crowding and glycine quenching.  

PubMed

In order to create macromolecular crowding resembling cells in mesopores and improve the covalent immobilization of penicillin acylase (PA), macromolecular reagents were covalently assembled on the walls of mesocellular silica foams (MCFs) and paralleled enzyme molecules under microwave irradiation at low temperatures. The effects of kind and content of macromolecules on immobilization and the characteristics of the immobilized enzyme were investigated carefully. The maximum specific activities of PA assembled with Dex 10 (Dextran, Mw 10000) (85.3 U/mg) and BSA (Bovine Serum Albumin) (112.7 U/mg) in MCFs under microwave irradiation were 1.73 and 1.31 times, respectively, that of PA solely immobilized by the conventional method. The optimum reaction temperature rose from 45-55 degrees C. Moreover, amino acids were used to quench excess activated groups in order to improve the thermostability of the immobilized enzyme. PA coassembled with Dex 10 in mesopores retained 88% of its initial catalytic activity after heating at 50 degrees C for 6 h, as a result of glycine quenching the excess activated groups. This biomolecule enhanced the thermostability of the enzyme preparation by 2-fold. A crowding environment resembling cells made from macromolecular reagents would be suitable for stabilizing the structure of PA and improving its catalytic activity. Glycine, a small biocompatible molecule, quenched the excess activated groups and modified the surface chemical properties of the mesoporous support, which would further favor the stability of PA at higher temperatures. Combining macromolecular crowding with glycine quenching was one of the efficient strategies adopted to improve microwave-assisted covalent PA immobilization. PMID:19269581

Wang, Anming; Zhou, Cheng; Du, Zhiqiang; Liu, Mingqing; Zhu, Shemin; Shen, Shubao; Ouyang, Pingkai

2009-03-01

314

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.

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

2012-01-01

315

Macromolecular Imaging Agents Containing Lanthanides: Can Conceptual Promise Lead to Clinical Potential?  

PubMed Central

Macromolecular magnetic resonance imaging (MRI) contrast agents are increasingly being used to improve the resolution of this noninvasive diagnostic technique. All clinically-approved T1 contrast agents are small molecule chelates of gadolinium [Gd(III)] that affect bound water proton relaxivity. Both the small size and monomeric nature of these agents ultimately limits the image resolution enhancement that can be achieved for both contrast enhancement and pharmacokinetic/biodistribution reasons. The multimeric nature of macromolecules, such as polymers, dendrimers, and noncovalent complexes of small molecule agents with proteins, have been shown to significantly increase the image contrast and resolution due to their large size and ability to incorporate multiple Gd(III) chlelation sites. Also, macromolecular agents are advantageous as they have the ability to be designed to be nontoxic, hydrophilic, easily purified, aggregation-resistant, and have controllable three-dimensional macromolecular structure housing the multiple lanthanide chelation sites. For these reasons, large molecule diagnostics have the ability to significantly increase the relaxivity of water protons within the targeted tissues and thus the image resolution for many diagnostic applications. The FDA approval of a contrast agent that consists of a reversible, non-covalent coupling of a small Gd(III) chelate with serum albumin for blood pool imaging (marketed under the trade names of Vasovist and Ablivar) proved to be one of the first diagnostic agent to capitalize on these benefits from macromolecular association in humans. However, much research and development is necessary to optimize the safety of these unique agents for in vivo use and potential clinical development. To this end, recent work in the field of polymer, dendrimer, and noncovalent complex-based imaging agents are reviewed herein and the future outlook of this field is discussed.

Bryson, Joshua; Reineke, Jeffrey W.; Reineke, Theresa M.

2012-01-01

316

Nuclear magnetic relaxation and structure of aqueous solutions  

Microsoft Academic Search

By the interpretation of the intermolecular nuclear magnetic relaxation rate of19F the orientation of the water molecules in the hydration sphere of F- can be determined. Similarly, the orientation of the water molecules around the methyl group of propionic acid in aqueous solution has been studied. Experiments are described which give information about the nature of association of solute in

H. G. Hertz

1973-01-01

317

Structure of supersaturated solution and crystal nucleation induced by diffusion  

NASA Astrophysics Data System (ADS)

The effect of a seed crystal on nucleation of L-alanine from a quiescent supersaturated solution was investigated. When a seed crystal was not used, nucleation did not occur at least for 5 h. When a seed crystal was introduced into the supersaturated solution with careful attention to avoid convection of the solution, fine crystals appeared at the place far from the seed crystal. At that time, there was no convection at the place that fine crystals appeared. Namely, there was no possibility that those fine crystals came from the surface of seed crystal. We supposed that nucleation was induced by directional diffusion of solute molecules caused by growth of the seed crystal. In order to prove this hypothesis, we designed an experiment using an apparatus composed of two compartments divided by a dialysis membrane that L-alanine molecules could freely permeate. Two supersaturated solutions having a supersaturation ratio of 1.2 and a smaller ratio were placed in the two compartments in the absence of seed crystals. This apparatus allowed the directional diffusion of solute molecules between two solutions. Nucleation occurred within 30 min. The frequency of nucleation among 7-times repeated experiments was in proportion to the difference of supersaturation ratio between the two solutions. This result poses a new mechanism of the secondary nucleation that the directional diffusion caused by growth of existing crystals induces nucleation.

Ooshima, Hiroshi; Igarashi, Koichi; Iwasa, Hideo; Yamamoto, Ren

2013-06-01

318

Aromatic moieties in meteoritic macromolecular materials: analyses by hydrous pyrolysis and ? 13C of individual compounds  

NASA Astrophysics Data System (ADS)

Hydrous pyrolysis, supercritical fluid extraction (SFE), gas chromatography-mass-spectrometry (GC-MS) and isotope ratio monitoring-gas chromatography-mass spectrometry (irm-GC-MS) were used to investigate the constitution of macromolecular materials in meteorites. Results from the carbonaceous chondrites Orgueil (CI1) and Cold Bokkeveld (CM2) were compared with those obtained previously from Murchison (CM2). Fragments of meteoritic macromolecular materials were produced by hydrous pyrolysis, extracted by SFE, and identified by GC-MS. The CI1 and CM2 hydrous pyrolysates all contain volatile aromatic compounds, some of which have aliphatic side chains, hydroxyl groups, and thiophene rings attached. The results indicate that the macromolecular materials in these meteorites are qualitatively similar. However, the pyrolysates show significant quantitative differences, with the products of ether linkages and condensed aromatic networks being less abundant in the more aqueously altered meteorites. In addition, the methylnaphthalene maturity parameter negatively correlates with aqueous alteration. These features are interpreted as the result of chemical reactions favored under hydrous conditions. Hence, the extent of aqueous alteration on the meteorite parent body appears to be the most important evolutionary stage in determining the final structure of macromolecular materials in the CI1 and CM2 meteorites. The carbon isotopic compositions of the fragments of macromolecular materials were determined by irm-GC-MS. ? 13C values for the hydrous pyrolysis products range from -25.5 to -10.2‰ for Orgueil and -22.9 to +4.0‰ for Cold Bokkeveld. These values can be compared to the -24.6 to -5.6‰ range obtained previously for Murchison. The low molecular weight components in each hydrous pyrolysate display shifts to increased 13C contents with carbon number. This indicates the production of simple organic entities by the preferential cracking of 12C- 12C bonds in more complex starting materials. The shifts extend from C 7 to C 8 for Orgueil and Cold Bokkeveld but from C 7 to C 10 for Murchison. Higher molecular weight components for all of the hydrous pyrolysates show a general trend of decreasing 13C content with carbon number. The higher molecular weight features can be explained by the preferential addition of 12C during the primary synthesis of the macromolecular materials. In addition, ? 13C values for the methylnaphthalenes are consistent with the addition of 12C to the most reactive site on the naphthalene parent molecule providing supporting evidence for synthesis. Hence, the macromolecular materials are composed of organic units created by both synthesis and cracking. Therefore, secondary processing by liquid water on the meteorite parent body exerts a strong control on the final molecular architecture of meteoritic macromolecular materials. Yet, the carbon isotopic compositions of some individual moieties may retain a record of primary synthesis.

Sephton, M. A.; Pillinger, C. T.; Gilmour, I.

2000-01-01

319

On the coupling of solvent characteristics to the electronic structure of solute molecules.  

PubMed

We present the results of a theoretical investigation focusing on the solvent structure surrounding the -1, 0 and +1 charged species of F, Cl, Br and I halogen atoms and F2, Cl2, Br2 and I2 di-halogen molecules in a methanol solvent and its influence on the electronic structure of the solute molecules. Our results show a large stabilizing effect arising from the solute-solvent interactions. Well-formed first solvation shells are observed for all species, the structure of which is strongly influenced by the charge of the solute species. Detailed analysis reveals that coordination number, CN, solvent orientation, ?, and solute-solvent distance, d, are important structural characteristics which are coupled to changes in the electronic structure of the solute. We propose that the fundamental chemistry of any solute species is generally regulated by these solvent degrees of freedom. PMID:24435016

Bogatko, Stuart; Cauët, Emilie; Geerlings, Paul; De Proft, Frank

2014-02-28

320

Protein structural dynamics of photoactive yellow protein in solution revealed by pump-probe X-ray solution scattering.  

PubMed

Photoreceptor proteins play crucial roles in receiving light stimuli that give rise to the responses required for biological function. However, structural characterization of conformational transition of the photoreceptors has been elusive in their native aqueous environment, even for a prototype photoreceptor, photoactive yellow protein (PYP). We employ pump-probe X-ray solution scattering to probe the structural changes that occur during the photocycle of PYP in a wide time range from 3.16 ?s to 300 ms. By the analysis of both kinetics and structures of the intermediates, the structural progression of the protein in the solution phase is vividly visualized. We identify four structurally distinct intermediates and their associated five time constants and reconstructed the molecular shapes of the four intermediates from time-independent, species-associated difference scattering curves. The reconstructed structures of the intermediates show the large conformational changes such as the protrusion of N-terminus, which is restricted in the crystalline phase due to the crystal contact and thus could not be clearly observed by X-ray crystallography. The protrusion of the N-terminus and the protein volume gradually increase with the progress of the photocycle and becomes maximal in the final intermediate, which is proposed to be the signaling state. The data not only reveal that a common kinetic mechanism is applicable to both the crystalline and the solution phases, but also provide direct evidence for how the sample environment influences structural dynamics and the reaction rates of the PYP photocycle. PMID:22304441

Kim, Tae Wu; Lee, Jae Hyuk; Choi, Jungkweon; Kim, Kyung Hwan; van Wilderen, Luuk J; Guerin, Laurent; Kim, Youngmin; Jung, Yang Ouk; Yang, Cheolhee; Kim, Jeongho; Wulff, Michael; van Thor, Jasper J; Ihee, Hyotcherl

2012-02-15

321

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

322

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

Microsoft Academic Search

Summary. 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

JON M. SORENSONb; ROBERT M. GLAESER; TERESA HEAD-GORDON

1999-01-01

323

Atomic force microscopy imaging of macromolecular complexes.  

PubMed

This chapter reviews amplitude modulation (AM) AFM in air and its applications to high-resolution imaging and interpretation of macromolecular complexes. We discuss single DNA molecular imaging and DNA-protein interactions, such as those with topoisomerases and RNA polymerase. We show how relative humidity can have a major influence on resolution and contrast and how it can also affect conformational switching of supercoiled DNA. Four regimes of AFM tip-sample interaction in air are defined and described, and relate to water perturbation and/or intermittent mechanical contact of the tip with either the molecular sample or the surface. Precise control and understanding of the AFM operational parameters is shown to allow the user to switch between these different regimes: an interpretation of the origins of topographical contrast is given for each regime. Perpetual water contact is shown to lead to a high-resolution mode of operation, which we term SASS (small amplitude small set-point) imaging, and which maximizes resolution while greatly decreasing tip and sample wear and any noise due to perturbation of the surface water. Thus, this chapter provides sufficient information to reliably control the AFM in the AM AFM mode of operation in order to image both heterogeneous samples and single macromolecules including complexes, with high resolution and with reproducibility. A brief introduction to AFM, its versatility and applications to biology is also given while providing references to key work and general reviews in the field. PMID:23086883

Santos, Sergio; Billingsley, Daniel; Thomson, Neil

2013-01-01

324

Analytical Solution to Diffraction Problems Involving Periodically Structured Objects.  

National Technical Information Service (NTIS)

A rigorous analysis of diffraction by rectangularly profiled, dielectric gratings is presented. An analytical solution is obtained for the total electromagnetic field. The approach presented can readily be extended to computations for metallic gratings an...

M. Akbari T. Magath

2000-01-01

325

Rectal and vaginal immunization with a macromolecular multicomponent peptide vaccine candidate for HIV1 infection induces HIVspecific protective immune responses  

Microsoft Academic Search

An effective vaccine for human immunodeficiency virus (HIV) is needed to stimulate the immune response of the genital mucus to prevent mucosal transmission of the virus. We have developed a macromolecular multicomponent peptide vaccine candidate, VC1. Both rectal and vaginal immunization of VC1 mixed with cholera toxin (CT) induced HIV-1-specific IgA antibody in mouse fecal extract solution and vaginal wash.

Hidenori Kato; Hiroki Bukawa; Eri Hagiwara; Ke-Qin Xin; Kenji Hamajima; Susumu Kawamoto; Mitsugu Sugiyama; Mitsuru Sugiyama; Etsunosuke Noda; Masanosuke Nishizaki; Kenji Okuda

2000-01-01

326

A structure based configuration tool: drive solution designer - DSD  

Microsoft Academic Search

In this paper, we describe the configuration tool Drive Solution Designer (DSD). The DSD is used by sales engineers of the company Lenze AG (www.lenze.com) for the configuration of complex drive systems in order to make on-site offers together with the customer. The aim of this process is to generate a consistent solution which fulfills the functional requirements of the

Christoph Ranze; Thorsten Scholz; Thomas Wagner; Andreas Günter; Otthein Herzog; Oliver Hollmann; Christoph Schlieder; Volker Arlt

327

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

Microsoft Academic Search

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

Y. C.. Chen; J. C. Feng; H. J. Liu

2007-01-01

328

Abundant exact solution structures of the Nizhnik-Novikov-Veselov equation  

NASA Astrophysics Data System (ADS)

Using the extended homogeneous balance method, we have obtained abundant exact solution structures of a (2+1)-dimensional integrable model, the Nizhnik-Novikov-Veselov equation. By means of leading order terms analysis, the nonlinear transformations of the Nizhnik-Novikov-Veselov equation are given first and then some special types of single solitary wave solution and multisoliton-like solutions are constructed.

Zhang, Jie-fang

2001-10-01

329

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

330

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

PubMed Central

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 flexible helical hairpin formed by a 32-residue insertion, which could determine substrate specificity. By using the Josephin structure and the availability of NMR chemical shift assignments, we have mapped the enzyme active site by using the typical cysteine protease inhibitors, transepoxysuccinyl-l-eucylamido-4-guanidino-butane (E-64) and [l-3-trans-(propylcarbamyl)oxirane-2-carbonyl]-l-isoleucyl-l-proline (CA-074). We also demonstrate that the specific interaction of Josephin with the ubiquitin-like domain of the ubiquitin- and proteasome-binding factor HHR23B involves complementary exposed hydrophobic surfaces. The structural similarity with other deubiquitinating enzymes suggests a model for the proteolytic enzymatic activity of ataxin-3.

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

2005-01-01

331

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

332

The structure of water in solutions containing di- and trivalent cations by empirical potential structure refinement.  

PubMed

Empirical potential structure refinement (EPSR) has been used to build experimentally consistent models of a range of electrolyte solutions containing di- and trivalent cations: Cu(ClO4)2 at concentrations of 0.5 and 2.0 m, and Cr(NO3)3, YCl3 and LaCl3 at a concentration of 1.0 m. The resulting models are used to investigate the perturbation of these electrolytes on the pair distribution and triplet angle correlations between solvent water molecules, compared with those found in the pure solvent. The results elucidate the differences that derive from the reflected range of highly structured local cation environments and provide a complementary viewpoint on the hydration shell geometries. PMID:24141281

Bowron, Daniel T; Moreno, Sofia Díaz

2013-11-13

333

TROSY in NMR studies of the structure and function of large biological macromolecules  

Microsoft Academic Search

Transverse relaxation-optimized spectroscopy (TROSY), in combination with various isotope-labeling techniques, has opened avenues to study biomolecules with molecular masses of up to 1000000Da by solution NMR. Important recent applications of TROSY include the structure determination of membrane proteins in detergent micelles, structural and functional studies of large proteins in both monomeric form and macromolecular complexes, and investigations of intermolecular interactions

César Fernández; Gerhard Wider

2003-01-01

334

STRUCTURE, VIBRATIONAL, AND CALORICAL PROPERTIES OF FULLERENE C60IN TOLUENE SOLUTION  

Microsoft Academic Search

The structure, vibrational and calorical properties of fullerene C60 in toluene solution were investigated both experimentally and theoretically in detail. The aggregation kinetics results indicated that the structure of C60 aggregates in toluene could be described as a fractal system. The electronic absorption spectra of C60 toluene solution with different concentration testify to the molecular character of absorption. The vibrational

Yu I. Prylutskyy; S. S. Durov; L. A. Bulavin; I. I. Adamenko; K. O. Moroz; A. Graja; A. Bogucki; P. Scharf

2001-01-01

335

Developing Force Fields from the Microscopic Structure of Solutions  

PubMed Central

We have been developing force fields designed for the eventual simulation of peptides and proteins using the Kirkwood-Buff (KB) theory of solutions as a guide. KB theory provides exact information on the relative distributions for each species present in solution. This information can also be obtained from computer simulations. Hence, one can use KB theory to help test and modify the parameters commonly used in biomolecular studies. A series of small molecule force fields representative of the fragments found in peptides and proteins have been developed. Since this approach is guided by the KB theory, our results provide a reasonable balance in the interactions between self-association of solutes and solute solvation. Here, we present our progress to date. In addition, our investigations have provided a wealth of data concerning the properties of solution mixtures, which is also summarized. Specific examples of the properties of aromatic (benzene, phenol, p-cresol) and sulfur compounds (methanethiol, dimethylsulfide, dimethyldisulfide) and their mixtures with methanol or toluene are provided as an illustration of this kind of approach.

Ploetz, Elizabeth A.; Bentenitis, Nikolaos; Smith, Paul E.

2009-01-01

336

Impact of Phenolic Antioxidants on Structural Properties of Micellar Solutions  

Microsoft Academic Search

Antioxidants solubilized in micellar solutions can change micellar properties like the size and shape of micelles, critical micellar concentration (cmc) and viscosity. Interactions arising between antioxidants and the surfactant determine the locations of antioxidants and vice versa. The location and interaction are dependent on the type of both the antioxidant and surfactant. Influences of various antioxidants on the physical and

Anja Heins; Vasil M. Garamus; Bernd Steffen; Heiko Stöckmann; Karin Schwarz

2006-01-01

337

Macromolecular Topography Leaps into the Digital Age  

NASA Technical Reports Server (NTRS)

A low-cost, real-time digital topography system is under development which will replace x-ray film and nuclear emulsion plates. The imaging system is based on an inexpensive surveillance camera that offers a 1000x1000 array of 8 im square pixels, anti-blooming circuitry, and very quick read out. Currently, the system directly converts x-rays to an image with no phosphor. The system is small and light and can be easily adapted to work with other crystallographic equipment. Preliminary images have been acquired of cubic insulin at the NSLS x26c beam line. NSLS x26c was configured for unfocused monochromatic radiation. Six reflections were collected with stills spaced from 0.002 to 0.001 degrees apart across the entire oscillation range that the reflections were in diffracting condition. All of the reflections were rotated to the vertical to reduce Lorentz and beam related effects. This particular CCD is designed for short exposure applications (much less than 1 sec) and so has a relatively high dark current leading to noisy raw images. The images are processed to remove background and other system noise with a multi-step approach including the use of wavelets, histogram, and mean window filtering. After processing, animations were constructed with the corresponding reflection profile to show the diffraction of the crystal volume vs. the oscillation angle as well as composite images showing the parts of the crystal with the strongest diffraction for each reflection. The final goal is to correlate features seen in reflection profiles captured with fine phi slicing to those seen in the topography images. With this development macromolecular topography finally comes into the digital age.

Lovelace, J.; Bellamy, H.; Snell, E. H.; Borgstahl, G.

2003-01-01

338

Davisson-Germer Prize in Atomic or Surface Physics Lecture: Line 'Em All Up: Macromolecular Assembly at Liquid Interfaces  

NASA Astrophysics Data System (ADS)

Advances in our molecular level understanding of the ubiquitous fluid interface comprised of a hydrophobic fluid medium, and an aqueous solution of soluble ions and solutes has been slow until recently. This more recent upsurge in interest and progress comes from advances in both experimental and computational techniques as well as the increasingly important role that this interface is playing in such areas as green chemistry, nanoparticle synthesis, improved oil and mineral recovery and water purification. The presentation will focus on our most recent efforts in understanding (1) the molecular structure of the interface between two immiscible liquids, (2) the penetration of aqueous phase ions into the interfacial region and their effect on its properties, and (3) the structure and dynamics of the adsorption of surfactants, polymers and nanoparticles at this interface. To gain insights into these processes we use a combination of vibrational sum frequency spectroscopy, surface tension measurements using the pendant drop method, and molecular dynamics simulations. The results demonstrate that weak interactions between interfacial oil and water molecules create an interface that exhibits a high degree of molecular structuring and ordering, and with properties quite different than what is observed at the air-water interface. As a consequence of these interfacial oil-water interactions, the interface provides a unique environment for the adsorption and assembly of ions, polymers and nanoparticles that are drawn to its inner-most regions. Examples of our studies that provide new insights into the unique nature of adsorption, adsorption dynamics and macromolecular assembly at this interface will be provided.

Richmond, Geraldine

2013-03-01

339

Neutron Diffraction, Isotopic Substitution and the Structure of Aqueous Solutions  

Microsoft Academic Search

The structural properties of liquids that contain more than one atomic species are difficult to unravel. The essential reason for this is that conventional diffraction experiments measure a rather coarse average of all the 1\\/2nu(nu + 1) partial structure factors that characterize a liquid containing nu species. This paper describes the way that neutron diffraction experiments carried out on samples

J. E. Enderby

1980-01-01

340

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

341

A universal thermodynamic model of calculating mass action concentrations for structural units or ion couples in aqueous solutions and its applications in binary and ternary aqueous solutions  

Microsoft Academic Search

A universal thermodynamic model of calculating mass action concentrations for structural units or ion couples in ternary and binary strong electrolyte aqueous solution was developed based on the ion and molecule coexistence theory and verified in four kinds of binary aqueous solutions and two kinds of ternary aqueous solutions. The calculated mass action concentrations of structural units or ion couples

Xue-min YANG; Wei-jie ZHAO; Guo-ming CHAI; Han-jie GUO; Qiang ZHANG

2011-01-01

342

Study of the structure of aqueous solutions of ionic macromolecules by low-frequency Raman spectroscopy  

Microsoft Academic Search

Using low-frequency Raman spectroscopy, the structure of aqueous solutions of polyacrylic acid as a function of polyelectrolyte\\u000a concentration and chain length was studied. The fractal dimension of structures in aqueous solutions of polyacrylic acid with\\u000a different acid concentrations and polyion chain lengths was determined. The size of fractal regions in systems with different\\u000a structures was estimated.

A. Z. Bol’shagina; A. M. Saletskii; A. V. Chervyakov

2001-01-01

343

Structure in aqueous solutions of nonpolar solutes from the standpoint of scaled-particle theory  

Microsoft Academic Search

Underlying assumptions have been examined in scaled-particle theory for the case of a rigid-sphere solute in liquid water. As a result, it has been possible to improve upon Pierotti's corresponding analysis in a way that explicitly incorporates measured surface tensions and radial-distribution functions for pure water. It is pointed out along the way that potential energy nonadditivity should create an

Frank H. Stillinger

1973-01-01

344

NMR solution structure of the neurotrypsin Kringle domain.  

PubMed

Neurotrypsin is a multidomain protein that serves as a brain-specific serine protease. Here we report the NMR structure of its kringle domain, NT/K. The data analysis was performed with the BACUS (Bayesian analysis of coupled unassigned spins) algorithm. This study presents the first application of BACUS to the structure determination of a 13C unenriched protein for which no prior experimental 3D structure was available. NT/K adopts the kringle fold, consisting of an antiparallel beta-sheet bridged by an overlapping pair of disulfides. The structure reveals the presence of a surface-exposed left-handed polyproline II helix that is closely packed to the core beta-structure. This feature distinguishes NT/K from other members of the kringle fold and points toward a novel functional role for a kringle domain. Functional divergence among kringle domains is discussed on the basis of their surface and electrostatic characteristics. PMID:18956887

Ozhogina, Olga A; Grishaev, Alexander; Bominaar, Emile L; Patthy, László; Trexler, Maria; Llinás, Miguel

2008-11-25

345

Unusual structural features revealed by the solution NMR structure of the NLRC5 caspase recruitment domain.  

PubMed

The cytosolic nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs) are key sensors for bacterial and viral invaders and endogenous stress signals. NLRs contain a varying N-terminal effector domain that regulates the downstream signaling events upon its activation and determines the subclass to which a NLR member belongs. NLRC5 contains an unclassified N-terminal effector domain that has been reported to interact downstream with the tandem caspase recruitment domain (CARD) of retinoic acid-inducible gene I (RIG-I). Here we report the solution structure of the N-terminal effector domain of NLRC5 and in vitro interaction experiments with the tandem CARD of RIG-I. The N-terminal effector domain of NLRC5 adopts a six ?-helix bundle with a general death fold, though it displays specific structural features that are strikingly different from the CARD. Notably, ?-helix 3 is replaced by an ordered loop, and ?-helix 1 is devoid of the characteristic interruption. Detailed structural alignments between the N-terminal effector domains of NLRC5 with a representative of each death-fold subfamily showed that NLRC5 fits best to the CARD subfamily and can be called an atypical CARD. Due to the specific structural features, the atypical CARD also displays a different electrostatic surface. Because the shape and charge of the surface is crucial for the establishment of a homotypic CARD-CARD interaction, these specific structural features seem to have a significant effect on the interaction between the atypical CARD of NLRC5 and the tandem RIG-I CARD. PMID:24815518

Gutte, Petrus G M; Jurt, Simon; Grütter, Markus G; Zerbe, Oliver

2014-05-20

346

Aggregation Behavior of Copolymer Containing Sulfobetaine Structure in Aqueous Solution  

Microsoft Academic Search

Copolymers containing sulfobetaine (P(AM\\/DMAPS)) were synthesized by aqueous copolymerization of acrylamide with 3-[N-(2-methacroyloylethyl)-N,N- dimethylammonio]-propane sulfonate. Aggregation and disaggregation of P(AM\\/ DMAPS) copolymer in aqueous solution as a function of copolymer concentration, added salts, and temperature were studied by dynamic laser light scattering. P(AM\\/DMAPS) copolymers exist as a mixture of individual chains and interchain aggregation in deionized water. At low copolymer

Yu-Ju Che; Yebang Tan; Jie Cao; Gui-Ying Xu

2010-01-01

347

A Structure Based Configuration Tool: Drive Solution Designer - DSD  

Microsoft Academic Search

In this paper, we describe the configuration tool Drive Solu- tion Designer (DSD). The DSD is used by sales engineers of the company Lenze AG (www.lenze.com) for the configu- ration of complex drive systems in order to make on-site of- fers together with the customer. The aim of this process is to generate a consistent solution which fulfills the func-

K. Christoph Ranze; Thorsten Scholz; Thomas Wagner; Andreas Günter; Otthein Herzog; Oliver Hollmann; Christoph Schlieder; Volker Arlt

2002-01-01

348

Chemical Solution Depositionof Layer-Structured Ferroelectric Thin Films  

Microsoft Academic Search

Ferroelectric rare-earth-doped Bi 4Ti 3O 12 thin films have been successfully prepared on Si-based substrates by using metallo-organic precursor solutions. The pyrolysis behavior of (Bi, R) 4Ti 3O 12 precursors depends upon the starting rare earth source, which strongly affects the surface morphology of the synthesized film. Among the (Bi, R) 4Ti 3O 12 films, BNT thin films reveal the

Shin-ichi Hirano; Takashi Hayashi; Wataru Sakamoto; Koichi Kikuta; Toshinobu Yogo

349

Integrated Force Method Solution to Indeterminate Structural Mechanics Problems  

NASA Technical Reports Server (NTRS)

Strength of materials problems have been classified into determinate and indeterminate problems. Determinate analysis primarily based on the equilibrium concept is well understood. Solutions of indeterminate problems required additional compatibility conditions, and its comprehension was not exclusive. A solution to indeterminate problem is generated by manipulating the equilibrium concept, either by rewriting in the displacement variables or through the cutting and closing gap technique of the redundant force method. Compatibility improvisation has made analysis cumbersome. The authors have researched and understood the compatibility theory. Solutions can be generated with equal emphasis on the equilibrium and compatibility concepts. This technique is called the Integrated Force Method (IFM). Forces are the primary unknowns of IFM. Displacements are back-calculated from forces. IFM equations are manipulated to obtain the Dual Integrated Force Method (IFMD). Displacement is the primary variable of IFMD and force is back-calculated. The subject is introduced through response variables: force, deformation, displacement; and underlying concepts: equilibrium equation, force deformation relation, deformation displacement relation, and compatibility condition. Mechanical load, temperature variation, and support settling are equally emphasized. The basic theory is discussed. A set of examples illustrate the new concepts. IFM and IFMD based finite element methods are introduced for simple problems.

Patnaik, Surya N.; Hopkins, Dale A.; Halford, Gary R.

2004-01-01

350

Structure of human insulin monomer in water\\/acetonitrile solution  

Microsoft Academic Search

Here we present evidence that in water\\/acetonitrile solvent detailed structural and dynamic information can be obtained for\\u000a important proteins that are naturally present as oligomers under native conditions. An NMR-derived human insulin monomer structure\\u000a in H2O\\/CD3CN, 65\\/35 vol%, pH 3.6 is presented and compared with the available X-ray structure of a monomer that forms part of a hexamer\\u000a (Acta Crystallogr.

Wojciech Bocian; Jerzy Sitkowski; El?bieta Bednarek; Anna Tarnowska; Robert Kaw?cki; Lech Kozerski

2008-01-01

351

Effect of Escherichia coli enterotoxins on macromolecular absorption.  

PubMed Central

Macromolecular absorption of gliadin, a wheat protein and alpha lactalbumin, a milk protein was evaluated in control and Escherichia coli enterotoxin (heat-stable, heat-labile, and both heat-stable and heat-labile enterotoxin) treated mice. The peak concentration of gliadin and lactalbumin was two hours and three hours after their ingestion, respectively. There was also a significant increase (p < 0.01) in the absorption of both the proteins in all the three toxin treated groups compared with the control group. These results suggest that intestinal permeability and macromolecular absorption changes after E coli infection.

Verma, M; Majumdar, S; Ganguly, N K; Walia, B N

1994-01-01

352

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.

Heroux, 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

353

A macromolecular prodrug strategy for combinatorial drug delivery.  

PubMed

A novel macromolecular prodrug strategy was developed for the combinatorial delivery of two poorly water-soluble drugs, dexamethasone and doxorubicin. In this work, dexamethasone was firstly conjugated onto a water-soluble modified polysaccharide by an acid-labile hydrazone linkage. The resultant macromolecular prodrug had an amphiphilic character and could self-assemble into spherical polymeric micelles in aqueous system. With these micelles, doxorubicin was then encapsulated into their hydrophobic cores. For the conjugated dexamethasone and encapsulated doxorubicin, they could exhibit independent and acid-sensitive release characteristics. For the doxorubicin-loaded prodrug micelles, they were easily be internalized by living cells and showed obvious antitumor activity. PMID:24407691

Li, Nan-Nan; Lin, Jiantao; Gao, Di; Zhang, Li-Ming

2014-03-01

354

High resolution solution structure of apo calcyclin and structural variations in the S100 family of calcium-binding proteins  

Microsoft Academic Search

The three-dimensional solution structure of apo rabbit lung calcyclin has been refined to high resolution through the use of heteronuclear NMR spectroscopy and 13C,15N- enriched protein. Upon completing the assignment of virtually all of the 15N, 13C and 1H NMR resonances, the solution structure was determined from a combination of 2814 NOE- derived distance constraints, and 272 torsion angle constraints

Lena Mäler; Barbara C. M. Potts; Walter J. Chazin

1999-01-01

355

Steady flows in solar magnetic structures - a class of exact MHD solutions.  

NASA Astrophysics Data System (ADS)

A class of exact solutions to the steady, two-dimensional magnetohydrodynamic equations in a cylindrical geometry is presented. These may model both closed and open magnetic structures found in the solar atmosphere. For closed structures, it is found that increasing the flow speed causes the summit of the arcade of closed magnetic fieldlines to rise. Parameter ranges also exist where the solution has regions of open and closed field, and so the solutions may be relevant for modelling flows in solar magnetic structures such as coronal streamers, X-ray bright points, coronal plumes and coronal holes.

de Ville, A.; Priest, E. R.

1991-11-01

356

Analysis of the structure of acetonitrile aqueous solutions based on study of their volumetric elastic properties  

NASA Astrophysics Data System (ADS)

The evolution of the structure of acetonitrile aqueous solutions is investigated by analyzing the concentration and temperature dependences of density, ultrasound velocity, adiabatic compressibility, excess molar volume, and excess adiabatic compressibility. It is shown that, the region in which solutions exist can be divided into five intervals that differ by solution structure. The structural features are described for each of them. It is found that in the 0.1 ? x ? 0.9 range of acetonitrile mole fractions, excess adiabatic compressibility isotherms behave abnormally: its absolute value increases with temperature, testifying to the important role played by the CH3 group of the amide residue of acetonitrile in molecular interactions.

Abramovich, A. I.; Lanshina, L. V.

2014-05-01

357

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

358

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

NASA Astrophysics Data System (ADS)

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.

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

2013-01-01

359

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

360

Automatic protein structure solution from weak X-ray data  

NASA Astrophysics Data System (ADS)

Determining new protein structures from X-ray diffraction data at low resolution or with a weak anomalous signal is a difficult and often an impossible task. Here we propose a multivariate algorithm that simultaneously combines the structure determination steps. In tests on over 140 real data sets from the protein data bank, we show that this combined approach can automatically build models where current algorithms fail, including an anisotropically diffracting 3.88?Å RNA polymerase II data set. The method seamlessly automates the process, is ideal for non-specialists and provides a mathematical framework for successfully combining various sources of information in image processing.

Skubák, Pavol; Pannu, Navraj S.

2013-11-01

361

Sucrose-water mixture: From thermodynamics to solution structure  

NASA Astrophysics Data System (ADS)

What is the structure of sucrose-water mixture? I employ an exact statistical thermodynamic theory (Kirkwood-Buff theory) to calculate information regarding sucrose-water, water-water and sucrose-sucrose interactions solely from volumetric and osmometric data. We found that (i) Long-ranged hydration structure, beyond the first hydration shell, influences thermodynamics; (ii) The inferred minimum of the activity coefficient of water at the high sucrose concentration is due to the increases in the self association of water. These findings from a rigorous theory are consistent with previous simulation studies.

Shimizu, Seishi

2013-09-01

362

Solution Structure and Stability of Tryptophan-Containing Nucleopeptide Duplexes  

Microsoft Academic Search

Covalently linked peptide ± oligonucleotide hybrids were used as models for studying tryptophan ± DNA interactions. The structure and stability of several hybrids in which peptides and oligonucleo- tides are linked through a phosphodiester bond between the hydroxy group of a homoserine (Hse) side chain and the 3-end of the oligonucleotide, have been studied by both NMR and CD spectroscopy

Irene Gómez-Pinto; Vicente Marchán; Federico Gago; Anna Grandas; Carlos González

2003-01-01

363

The nanoheterogeneous structure of aqueous solutions of n-propanol  

Microsoft Academic Search

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

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

2009-01-01

364

Effect of snow structure on water flow and solute transport  

Microsoft Academic Search

Water flow through a melting snow pack modifies its structure and stability and affects the release of water and nutrients into soils and surface waters. Field and laboratory observations indicate a large spatial variability on various scales of the liquid water content and flow, a dominant system feature currently not included in numerical models. We investigated experimentally water and dye

Peter A. Waldner; Martin Schneebeli; Ute Schultze-Zimmermann; Hannes Flühler

2004-01-01

365

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

366

Composition and structure of iron oxidation surface layers produced in weak acidic solutions  

Microsoft Academic Search

Although oxidation\\/passivation of iron in basic solution has been extensively investigated, there is very little information on iron corrosion in weak acidic solutions. In this work, iron surface composition and structure, produced in aerobic aqueous solutions ranging from pH 2 to 5, were determined in detail by the use of infrared external reflection spectroscopy, X-ray photoelectron spectroscopy and scanning electron

Gonzalo Montes Atenas; Ela Mielczarski; Jerzy A. Mielczarski

2005-01-01

367

Characteristics, performance and stability of polyethersulfone ultrafiltration membranes prepared by phase separation method using different macromolecular additives  

Microsoft Academic Search

Polyethersulfone (PES) ultrafiltration (UF) membranes were prepared by non-solvent-induced phase separation (NIPS) method using different macromolecular additives, polyvinylpyrrolidone (PVP), poly(ethylene glycol) (PEG) and poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (Pluronic®, Plu). Their effects on membrane structure and their stability in the polymer membrane matrix as well as the resulting membrane performance were systematically compared in order to determine the additive that should

Heru Susanto; Mathias Ulbricht

2009-01-01

368

Macromolecular Assemblage of Aminoacyl-tRNA Synthetases: Quantitative Analysis of Protein-Protein Interactions and Mechanism of Complex Assembly  

Microsoft Academic Search

The structure of the mammalian multi-synthetase complex was investigated in vitro using qualitative and quantitative approaches. This macromolecular assemblage comprises the bifunctional glutamyl-prolyl-tRNA synthetase, the seven monospecific isoleucyl, leucyl, methionyl, glutaminyl, lysyl, arginyl and aspartyl-tRNA synthetases, and the three auxiliary p43, p38 and p18 proteins. The scaffold p38 protein was expressed in Escherichia coli and purified to homogeneity as a

Jean-Charles Robinson; Pierre Kerjan; Marc Mirande

2000-01-01

369

Effects of Sericite Modified by Macromolecular Dispersant on the Thermal, Mechanical and Electrical Properties of the NR\\/SBR Composites  

Microsoft Academic Search

A new hydrosoluble macromolecular dispersant and modifier, poly(ethylene glycol)-maleic anhydride-acrylic acid (PEG-MA-AA) terpolymer was synthesized via ring-opening reaction and free radical polymerization. The chemical structure of the PEG-MA-AA terpolymer was confirmed by Fourier transform infrared (FTIR) spectra and nuclear magnetic resonance spectroscopy (NMR), and its average molecular weight was determined by gel permeation chromatography (GPC). Modified sericite (MSE) was synthesized

Weizhao Hu; Ruxia; Yuchuan Zhang; Fangshan Li; Xu He

2011-01-01

370

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

371

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

372

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

373

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

374

Structure of the solution set for a class of semilinear elliptic equations with asymptotic linear nonlinearity  

Microsoft Academic Search

We consider a semilinear elliptic equation with asymptotic linear nonlinearity applying bifurcation theory and spectral analysis. We obtain the exact multiplicity of the positive solutions and a very precise structure of the solution set, which improves the previous knowledge of the problem.

Jia Duo; Junping Shi; Yuwen Wang

2008-01-01

375

Stabilization of the structure of aqueous solutions by nonelectrolyte molecules, and permittivity  

Microsoft Academic Search

We measured the permittivity s' (frequency 9400 MHz) to study the stabilization of the structure of water by methyl alcohol molecules. We found that additions of methyl alcohol act on ~' of water and aqueous solutions of electrolytes in the same way as a reduction in temperature. Methyl alcohol reduces the hydration (dehydration) of the ions in solutions, Two mechanisms

P. S. Yastremskii; O. Ya. Samoilov

1963-01-01

376

Solution spectroelectrochemical cell for in situ X-ray absorption fine structure.  

National Technical Information Service (NTIS)

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 ...

M. R. Antonio L. Soderholm I. Song

1995-01-01

377

Protein Folding, Protein Structure and the Origin of Life: Theoretical Methods and Solutions of Dynamical Problems.  

National Technical Information Service (NTIS)

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 calcu...

D. L. Weaver

1982-01-01

378

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)] [South African Nuclear Energy Corporation - Necsa, Building 1900, P.O. Box 582, 0001 Pretoria (South Africa)

2013-07-01

379

The Measurement of Heat Capacity Differences Due to the Change of Water Structure in Aqueous Solutions of Organic Compounds  

Microsoft Academic Search

In order to observe more directly the structural organization of water molecules around a non-polar molecule in an aqueous\\u000a solution, heat capacity differences between two kinds of solutions (solution I and II) of quaternary ammonium salts were measured.\\u000a In the solution I stable water structure was retained as much as possible and in the solution II water structure was destroyed

H. Nakayama; K. Aida

1999-01-01

380

Atomic detail brownian dynamics simulations of concentrated protein solutions with a mean field treatment of hydrodynamic interactions.  

SciTech Connect

High macromolecular concentrations are a distinguishing feature of living organisms. Understanding how the high concentration of solutes affects the dynamic properties of biological macromolecules is fundamental for the comprehension of biological processes in living systems. In this paper, we describe the implementation of mean field models of translational and rotational hydrodynamic interactions into an atomically detailed many-protein brownian dynamics simulation method. Concentrated solutions (30-40% volume fraction) of myoglobin, hemoglobin A, and sickle cell hemoglobin S were simulated, and static structure factors, oligomer formation, and translational and rotational self-diffusion coefficients were computed. Good agreement of computed properties with available experimental data was obtained. The results show the importance of both solvent mediated interactions and weak protein-protein interactions for accurately describing the dynamics and the association properties of concentrated protein solutions. Specifically, they show a qualitative difference in the translational and rotational dynamics of the systems studied. Although the translational diffusion coefficient is controlled by macromolecular shape and hydrodynamic interactions, the rotational diffusion coefficient is affected by macromolecular shape, direct intermolecular interactions, and both translational and rotational hydrodynamic interactions.

Mereghetti, Paolo; Wade, Rebecca C.

2012-07-26

381

The nanoheterogeneous structure of aqueous solutions of n -propanol  

Microsoft Academic Search

The results of positron spectroscopy and molecular light scattering studies, the data on radiationchemical yields and optical\\u000a absorption spectra of solvated electrons formed under the action of ionizing radiation, and the data on the concentration\\u000a dependences of viscosity, adiabatic compressibility, the velocity of sound, and partial molar volume were used to determine\\u000a the structure of water-n-propanol mixtures. The conclusion was

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

2009-01-01

382

Relationship between the freezing points and structure of aqueous solutions  

Microsoft Academic Search

UDC 532.77 The aqueous nonelectrolyte systems CsHlzN 4- HaG, DMFA - HzO, and C 6 HlzN 4 -n-C4 HgOH- HzO have been studied by the cryoscopic method over a wide range of concentrations. The diagrams obtained have been interpreted on the basis of the assumption that there is a direct relationship between the crystallization temperatures and the structural changes in

A. A. Énnan; V. A. Lapshin

1972-01-01

383

The promise of macromolecular crystallization in microfluidic chips  

Microsoft Academic Search

Microfluidics, or lab-on-a-chip technology, is proving to be a powerful, rapid, and efficient approach to a wide variety of bioanalytical and microscale biopreparative needs. The low materials consumption, combined with the potential for packing a large number of experiments in a few cubic centimeters, makes it an attractive technique for both initial screening and subsequent optimization of macromolecular crystallization conditions.

Mark van der Woerd; Darren Ferree; Marc Pusey

2003-01-01

384

Ray-tracing analysis of capillary concentrators for macromolecular crystallography.  

PubMed

The use of capillary concentrators as X-ray condensers specifically for macromolecular X-ray diffraction experiments using synchrotron radiation is evaluated. Monocapillary and polycapillary designs are assessed by ray-tracing analysis to evaluate how effectively these capillary concentrators can increase the X-ray intensity onto a 50 micro m crystal. PMID:15263664

Thiel, D J

1998-05-01

385

A Natural Documentation Retrieval System for Macromolecular Chemistry  

ERIC Educational Resources Information Center

An indexing system for chemistry and technology of macromolecular substances is sketched out, whose characteristics are convenience of use and low cost. The selection mechanism consists of a set of optical coincidence cards. The selection is a result of 15 years experience in the German Plastics Institute. (13 references) (Author)

Ulbrich, Raimund; Wierer, Jutta

1972-01-01

386

Hydrophobic effects in the water network structure of aqueous solutions of a semiclathrate molecule  

Microsoft Academic Search

In-phase collective small amplitude proton motions are observed in the OH stretching Raman spectrum of the semiclathrate crystalline hydrate of tetra-n-butyl ammonium hydroxide, its melt and aqueous solutions. These are quantified and used in dilute solutions as a probe of the network structure of water surrounding the molecule. Clear evidence of structural enhancement of the network is obtained in dilute

J. L. Green; M. G. Sceats; A. R. Lacey

1987-01-01

387

Structure discrimination for the C-terminal domain of Escherichia coli trigger factor in solution  

Microsoft Academic Search

NMR measurements can give important information on solution structure, without the necessity for a full-scale solution structure\\u000a determination. The C-terminal protein binding domain of the ribosome-associated chaperone protein trigger factor is composed\\u000a of non-contiguous parts of the polypeptide chain, with an interpolated prolyl isomerase domain. A construct of the C-terminal\\u000a domain of Escherichia coli trigger factor containing residues 113–149 and

Yong Yao; Gira Bhabha; Gerard Kroon; Mindy Landes; H. Jane Dyson

2008-01-01

388

Structures of bromoalkanes' photodissociation in solution by means of ultrafast extended x-ray absorption fine-structure spectroscopy  

PubMed Central

The structures of initial and final products of bromoalkanes' photodisociation reaction in cyclohexane solution have been measured with a bond length accuracy of 0.02 ? by means of ultrafast time-resolved extended x-ray absorption fine structure spectroscopy. The photoredaction mechanism is also discussed.

Oulianov, D. A.; Tomov, I. V.; Dvornikov, A. S.; Rentzepis, P. M.

2002-01-01

389

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

390

Borotungstate polyoxometalates: multinuclear NMR structural characterization and conversions in solutions.  

PubMed

The unique heteropolyanion [H(3)BW(13)O(46)](8-) (BW(13)), previously suggested on the basis of indirect evidence, and protonated lacunary heteropolyanion [HBW(11)O(39)](8-) (BW(11)) have been identified in aqueous solutions at pH 5-7.5 from NMR spectra. The pattern of tungsten-tungsten connectivities based on the analysis of the (2)J(W-O-W) coupling satellites in the (183)W NMR spectrum of BW(11), containing six peaks of relative intensities ?2:2:2:1:2:2, indicates that the latter is the ? isomer. The (17)O NMR spectrum confirms the protonated state of the polyanion with the proton delocalized on two out of four terminal O atoms surrounding the tungsten vacancy. The (183)W NMR spectrum of BW(13) contains seven peaks of relative intensities ?2:1:2:2:2:2:2 with additional large couplings due to the connectivity between BW(11) and [W(2)O(7)](2-) fragments. According to the (17)O NMR spectrum, two protons of [BW(13)O(46)H(3)](8-) are delocalized on the two terminal trans O atoms of the dimeric fragment while the third one is linked to its bridging O atom. The conversions of BW(11) and BW(13) in solution were followed by using (183)W NMR spectra at a "fingerprint" level. In the pH range from ?7.5 to 6, BW(11) transforms to BW(13), transforming further to [BW(12)O(40)](5-) (BW(12)) and [B(3)W(39)O(132)H(n)](n-21) (B(3)W(39)) in different ratios. Conversion of BW(13) to BW(12) proceeds through an intermediate complex of suggested composition [BW(11)O(39)·WO(2)](7-). At high acidity (pH ? 0), B(3)W(39) gradually decomposes into tungstic acid, BW(12) and H(3)BO(3). Polyanion BW(12) persists in the pH range ?0-7.5. PMID:21526755

Maksimovskaya, Raisa I; Maksimov, Gennadii M

2011-06-01

391

Macromolecular dynamics of conjugated polymer in donor-acceptor blends with charge transfer complex.  

PubMed

Donor-acceptor blends based on conjugated polymers are the heart of state-of-the-art polymer solar cells, and the control of the blend morphology is crucial for their efficiency. As the film morphology can inherit the polymer conformational state from solution, the approaches for probing and controlling the polymer conformational state in the blends are of high importance. In this study, we show that the macromolecular dynamics in solutions of the archetypical conjugated polymer, MEH-PPV, is essentially changed upon addition of an acceptor 2,4,7-trinitrofluorenone (TNF) by using dynamic light scattering (DLS). We have observed four new types of the macromolecular dynamics absent in the parent polymer determined by the polymer and acceptor content. The MEH-PPV?:?TNF ground-state charge-transfer complex (CTC) is suggested to result in these dynamics. In the dilute polymer solution, the CTC formation leads to slower dynamics as compared with the pristine polymer. This is evidence of aggregates formed by intercoil links that are the CTCs involving two conjugated segments of different coils with acceptor molecules being sandwiched between them. At low acceptor content, the aggregates are not stable but at high acceptor content, they are. In the semidilute solution at low acceptor content, the dynamics becomes faster as compared with the pristine polymer that is explained by confinement of the coupled motions of entangled polymer chains. At high acceptor content, the dynamics is far much slower with a characteristic long-range correlation at the scale 3-5 ?m that is explained by aggregation of polymer chains in clusters. One can expect that the DLS technique could become a useful tool to study the nano- and microstructure of donor-acceptor conjugated polymer blends to achieve controllable morphology in the corresponding blend films. PMID:21183986

Parashchuk, Olga D; Laptinskaya, Tatyana V; Paraschuk, Dmitry Yu

2011-03-01

392

Solution NMR structure of the 30S ribosomal protein S28E from Pyrococcus horikoshii  

Microsoft Academic Search

We report NMR assignments and solution structure of the 71-residue 30S ribosomal protein S28E from the archaean Pyrococcus horikoshii, target JR19 of the Northeast Structural Genomics Consortium. The struc- ture, determined rapidly with the aid of automated backbone resonance assignment (AutoAssign) and automated structure determination (AutoStructure) software, is characterized by a four-stranded -sheet with a classic Greek-key topology and an

James M. Aramini; Yuanpeng J. Huang; John R. Cort; Sharon Goldsmith-Fischman; Rong Xiao; Liang-Yu Shih; Chi K. Ho; Jinfeng Liu; Burkhard Rost; Barry Honig; Michael A. Kennedy; Thomas B. Acton; Gaetano T. Montelione

2003-01-01

393

In Vivo Measurement of Internal and Global Macromolecular Motions in Escherichia coli  

PubMed Central

We present direct quasielastic neutron scattering measurements, in vivo, of macromolecular dynamics in Escherichia coli. The experiments were performed on a wide range of timescales to cover the large panel of internal and self-diffusion motions. Three major internal processes were extracted at physiological temperature: a fast picosecond process that corresponded to restricted jump diffusion motions and two slower processes that resulted from reorientational motions occurring in ?40 ps and 90 ps, respectively. The analysis of the fast process revealed that the cellular environment leads to an appreciable increase in internal molecular flexibility and diffusive motion rates compared with those evaluated in fully hydrated powders. The result showed that the amount of cell water plays a decisive role in internal molecular dynamics. Macromolecular interactions and confinement, however, attenuate slightly the lubricating effect of water, as revealed by the decrease of the in vivo parameters compared with those measured in solution. The study demonstrated that standard sample preparations do not mimic accurately the physiological environment and suggested that intracellular complexity participates in functional dynamics necessary for biological activity. Furthermore, the method allowed the extraction of the self-diffusion of E. coli macromolecules, which presented similar parameters as those extracted for hemoglobin in red blood cells.

Jasnin, M.; Moulin, M.; Haertlein, M.; Zaccai, G.; Tehei, M.

2008-01-01

394

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

PubMed Central

Abstract Theoretical models predict that macromolecular crowding can increase protein folding stability, but depending on details of the models (e.g., how the denatured state is represented), the level of stabilization predicted can be very different. In this study, we represented the native and denatured states atomistically, with conformations sampled from explicit-solvent molecular dynamics simulations at room temperature and high temperature, respectively. We then designed an efficient algorithm to calculate the allowed fraction, f, when the protein molecule is placed inside a box of crowders. That a fraction of placements of the protein molecule is disallowed because of volume exclusion by the crowders leads to an increase in chemical potential, given by ?? = ?kBT lnf. The difference in ?? between the native and denatured states predicts the effect of crowding on the folding free energy. Even when the crowders occupied 35% of the solution volume, the stabilization reached only 1.5 kcal/mol for cytochrome b562. The modest stabilization predicted is consistent with experimental studies. Interestingly, a mixture of different sized crowders was found to exert a greater effect than the sum of the individual species of crowders. The stabilization of crowding on the binding stability of barnase and barstar, based on atomistic modeling of the proteins, was similarly modest. These findings have profound implications for macromolecular crowding inside cells.

Qin, Sanbo; Zhou, Huan-Xiang

2009-01-01

395

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.

Seeliger, Janine; Werkmuller, Alexander; Winter, Roland

2013-01-01

396

Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.  

PubMed

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; Lindner, Ariel B; Berry, Hugues

2013-04-01

397

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.

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

2013-01-01

398

Structural aggregates of rod-coil copolymer solutions  

NASA Astrophysics Data System (ADS)

The optoelectronic properties of rod-coil diblock copolymers with ?-conjugation are greatly affected by molecular packing, which is closely related to their micellar morphology. Self-assembly of rod-coil block copolymer ByAx in a selective solvent for its coil block is studied by using dissipative particle dynamics, where ByAx denotes the polymer comprising of y rodlike B beads and x coil-like A beads. The influences of polymer concentration, component compatibility, solvent quality for coil block, rod-block length, and ? - ? interaction on the resulting aggregate conformations are examined. It was found that distinctly different from coil-coil copolymers, the aggregates of rod-coil copolymers exhibit morphological and structural diversity induced by the intrinsically rigid nature of the rod blocks. In general, the aggregate adopts the overall shape of sphere, cylinder, perforated sheet, or network. The morphology of the rod-block domain within aggregate is even richer and the interesting structures such as porous sphere, spherical spiral, helical bundles, discrete chunks, and nematic cylinder are observed. The short-range order parameter indicates that as rod length is long enough, neighboring rods begin to orient parallel to one another and nematic domains appear. Moreover, in the presence of ? - ? interactions, the neighboring rods within the B domains become more coherently oriented and smectic domains can thus be formed.

Chou, Shih-Hao; Tsao, Heng-Kwong; Sheng, Yu-Jane

2011-01-01

399

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

400

Solution structure of proinsulin: connecting domain flexibility and prohormone processing.  

PubMed

The folding of proinsulin, the single-chain precursor of insulin, ensures native disulfide pairing in pancreatic beta-cells. Mutations that impair folding cause neonatal diabetes mellitus. Although the classical structure of insulin is well established, proinsulin is refractory to crystallization. Here, we employ heteronuclear NMR spectroscopy to characterize a monomeric analogue. Proinsulin contains a native-like insulin moiety (A- and B-domains); the tethered connecting (C) domain (as probed by {(1)H}-(15)N nuclear Overhauser enhancements) is progressively less ordered. Although the BC junction is flexible, residues near the CA junction exhibit alpha-helical-like features. Relative to canonical alpha-helices, however, segmental (13)C(alpha/beta) chemical shifts are attenuated, suggesting that this junction and contiguous A-chain residues are molten. We propose that flexibility at each C-domain junction facilitates prohormone processing. Studies of protease SPC3 (PC1/3) suggest that C-domain sequences contribute to cleavage site selection. The structure of proinsulin provides a foundation for studies of insulin biosynthesis and its impairment in monogenic forms of diabetes mellitus. PMID:20106974

Yang, Yanwu; Hua, Qing-Xin; Liu, Jin; Shimizu, Eri H; Choquette, Meredith H; Mackin, Robert B; Weiss, Michael A

2010-03-12

401

Shear-induced structure in polymer-clay nanocomposite solutions.  

PubMed

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, coupling between composition and stress leads to the formation of a macroscopic domain pattern, while the clay platelets orient with their surface normal parallel to the direction of vorticity. We discuss the shear-induced structure, steady-shear rheology, and oscillatory-shear response of these dynamic networks, and we offer a physical explanation for the mesoscale shear response. In contrast to flow-induced "banding" transitions, no stress plateau is observed in the region where macroscopic phase separation occurs. The observed platelet orientation is different from that reported for polymer-melt clay nanocomposites, which we attribute to effects associated with macroscopic phase separation under shear flow. PMID:15144824

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

2004-06-15

402

Structural aggregates of rod-coil copolymer solutions.  

PubMed

The optoelectronic properties of rod-coil diblock copolymers with ?-conjugation are greatly affected by molecular packing, which is closely related to their micellar morphology. Self-assembly of rod-coil block copolymer B(y)A(x) in a selective solvent for its coil block is studied by using dissipative particle dynamics, where B(y)A(x) denotes the polymer comprising of y rodlike B beads and x coil-like A beads. The influences of polymer concentration, component compatibility, solvent quality for coil block, rod-block length, and ?-? interaction on the resulting aggregate conformations are examined. It was found that distinctly different from coil-coil copolymers, the aggregates of rod-coil copolymers exhibit morphological and structural diversity induced by the intrinsically rigid nature of the rod blocks. In general, the aggregate adopts the overall shape of sphere, cylinder, perforated sheet, or network. The morphology of the rod-block domain within aggregate is even richer and the interesting structures such as porous sphere, spherical spiral, helical bundles, discrete chunks, and nematic cylinder are observed. The short-range order parameter indicates that as rod length is long enough, neighboring rods begin to orient parallel to one another and nematic domains appear. Moreover, in the presence of ?-? interactions, the neighboring rods within the B domains become more coherently oriented and smectic domains can thus be formed. PMID:21261388

Chou, Shih-Hao; Tsao, Heng-Kwong; Sheng, Yu-Jane

2011-01-21

403

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.

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

2008-01-01

404

Thermodynamic and structural aspects of sulfonamide crystals and solutions.  

PubMed

The crystal structures of three sulfonamides with the general structure 4-NH(2)-C(6)H(4)-SO(2)NH-C(6)H(4/3)-R (R = 4-Et; 4-OMe; 5-Cl-2-Me) have been determined by X-ray diffraction. On the basis of our previous data and the results obtained a comparative analysis of crystal properties was performed: molecular conformational states, packing architecture, and hydrogen bond networks using graph set notations. The thermodynamic aspects of the sulfonamide sublimation process have been studied by investigating the temperature dependence of vapor pressure using the transpiration method. A regression equation was derived describing the correlation between sublimation entropy terms and crystal density data calculated from X-ray diffraction results. Also correlations between sublimation Gibbs energies and melting points, on the one hand, and between sublimation enthalpies and fusion enthalpies at 298 K, on the other hand, were found. These dependencies give the opportunity to predict sublimation thermodynamic parameters by simple thermo-physical experiments (fusion characteristics). Solubility processes of the compounds in water, n-hexane, and n-octanol (as phases modeling various drug delivery pathways and different types of membranes) were investigated and corresponding thermodynamic functions were calculated as well. Thermodynamic characteristics of sulfonamide solvation were evaluated. For compounds with similar structures processes of transfer from one solvent to another one were studied by a diagram method combined with analysis of enthalpic and entropic terms. Distinguishing between enthalpy and entropy, as is possible through the present approach, leads to the insight that the contribution of these terms is different for different molecules (entropy- or enthalpy-determined). Thus, in contrast to interpretation of only the Gibbs energy of transfer, being extensively used for pharmaceuticals in the form of the partition coefficient (log P), the analysis of thermodynamic functions of the transfer process provides additional mechanistic information. This may be important for further evaluation of the physiological distribution of drug molecules and may provide a better understanding of biopharmaceutical properties of drugs. PMID:19408296

Perlovich, German L; Tkachev, Valery V; Strakhova, Nadezda N; Kazachenko, Vladimir P; Volkova, Tatyana V; Surov, Oleg V; Schaper, Klaus-Jürgen; Raevsky, Oleg A

2009-12-01

405

Support for Obtaining Satisfactory Design Solutions of Form and Structure by Applying the Emergent Form-Generation System  

Microsoft Academic Search

It is important to design in a short period of time efficiently as studies of concurrent engineering have been developed. Obtaining design solutions that satisfy an evaluation of form such as originality and structure such as strength (satisfactory design solutions of form and structure) are necessary. However, conventional structural optimization methods are difficult to obtain satisfactory design solutions of form

Masato INOUE; Yoshiyuki MATSUOKA

406

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

407

Solution structure of physiological Cu(His)2: novel considerations into imidazole coordination.  

PubMed

A disagreement on the mode of histidine binding to copper and the structure of [Cu(2+)(His)(2)] in solution still exists. Spectroscopic data in solution support a six-coordinate species with N4O2 donor atoms, while X-ray crystallography reveals five-coordinate N(3)O(2) donor atoms. We modified [Cu(2+)(His)(2)] in solution using diethyl pyrocarbonate (DEPC) and monitored the products spectrophotometrically and by mass spectrometry. Our spectrophotometric study indicates the presence of a free imidazole in the [Cu(2+)(His)(2)] complex in solution. Mass spectral characterization of a DEPC-modified [Cu(2+)(His)(2)] complex yielded a peak at 587.8 amu corresponding to three DEPC adducts. Taken together, our data indicate that the [Cu(2+)(His)(2)] complex in solution exists as a neutral five-coordinate structure with N3O2 donor atoms. PMID:19722687

Ginotra, Yamini P; Kulkarni, Prasad P

2009-08-01

408

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

409

Structure and solid solution properties of Cu–Ag nanoalloys  

NASA Astrophysics Data System (ADS)

The nanoparticle phase diagram of an immiscible system is studied at the atomic level. Cu–Ag clusters with sizes 1000 and 2000 atoms, resulting from a global minimum search and belonging to icosahedral and crystalline structural motifs, are considered. We present the statistical analysis of the effect of temperature on the solubility of the two elements based on Metropolis Monte Carlo importance sampling. Our results suggest that the relevance of bulk phase diagrams to nanoparticles is limited to cases where the internal stress distribution does not deviate very much from uniform (e.g. sufficiently large crystalline clusters). In the general case, the principal interdependence between partial phase compositions and the overall cluster composition in nanoparticle phase diagrams need to be taken into account.

Atanasov, Ivailo; Ferrando, Riccardo; Johnston, Roy L.

2014-07-01

410

Structure and solid solution properties of Cu-Ag nanoalloys.  

PubMed

The nanoparticle phase diagram of an immiscible system is studied at the atomic level. Cu-Ag clusters with sizes 1000 and 2000 atoms, resulting from a global minimum search and belonging to icosahedral and crystalline structural motifs, are considered. We present the statistical analysis of the effect of temperature on the solubility of the two elements based on Metropolis Monte Carlo importance sampling. Our results suggest that the relevance of bulk phase diagrams to nanoparticles is limited to cases where the internal stress distribution does not deviate very much from uniform (e.g. sufficiently large crystalline clusters). In the general case, the principal interdependence between partial phase compositions and the overall cluster composition in nanoparticle phase diagrams need to be taken into account. PMID:24918748

Atanasov, Ivailo; Ferrando, Riccardo; Johnston, Roy L

2014-07-01

411

Solution structure of the cAMP-dependent protein kinase  

SciTech Connect

This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project as Los Alamos National Laboratory (LANL). Protein phosphorylation is well established as one of the most important mechanisms of signal transduction and cellular regulation. Two of the key enzymes that catalyze these phosphorylation reactions are the cAMP- (PKA) and cGMP- (PKG) dependent protein kinases. PKA has served as the prototypic model of this class of enzymes that now comprises in excess of 300 phylogenetically related proteins. A large number of these protein kinases are critical for the regulation of cell function and a full analysis of their similarities and differences is essential to understand their diverse physiological roles. The cAMP-dependent protein kinase has the subunit structure R2C2, in which C and R refer to the catalytic and regulatory subunits, respectively. The cGMP-dependent protein kinase (PKG) is highly homologous to PKA but is distinguished from it by having the regulatory and catalytic domains on a contiguous polypeptide. The studies described here use small-angle scattering and Fourier Transform InfraRed (FTIR) spectroscopy to study domain movements and conformational changes in these enzymes in different functional states in order to elucidate the molecular bases for the regulation of their activities.

Trewhella, J.; Olah, G.A. [Los Alamos National Lab., NM (United States); Walsh, D.A.; Mitchell, R.D. [Univ. of California, Davis, CA (United States)

1998-12-31

412

Aggregation Behavior of Surfactants with Different Molecular Structures in Aqueous Solution: DPD Simulation Study  

Microsoft Academic Search

The aggregation behavior of surfactants with different molecular structures in aqueous solution was investigated by Dissipative Particle Dynamics (DPD) coarse-grained model simulation. With a simple surfactant model, we investigated how variations in micelle size and structures of surfactants influence their aggregation behavior. The obvious effects on the aggregation properties of surfactants caused by the variation of the hydrophobic or hydrophilic

Yiming Li; Haixia Zhang; Mutai Bao; Qingguo Chen

2012-01-01

413

Solution structure of the DNA-binding domain of TraM.  

PubMed

The solution structure of the DNA-binding domain of the TraM protein, an essential component of the DNA transfer machinery of the conjugative resistance plasmid R1, is presented. The structure has been determined using homonuclear 2-dimensional NMR spectroscopy as well as 15N labeled heteronuclear 2- and 3-dimensional NMR spectroscopy. It turns out that the solution structure of the DNA binding domain of the TraM protein is globular and dominantly helical. The very first amino acids of the N-terminus are unstructured. PMID:11258958

Stockner, T; Plugariu, C; Koraimann, G; Högenauer, G; Bermel, W; Prytulla, S; Sterk, H

2001-03-20

414

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

415

Defect structure of cubic solid solutions of alkaline earth and rare earth fluorides  

NASA Astrophysics Data System (ADS)

In this paper we will consider the disorder in some cubic solid solutions consisting of one of the alkaline earth fluorides and one of the rare earth fluorides. This is an attractive group of model materials, because these materials have a rather simple overall cubic structure. We will discuss the most important features of the structure of these solid solutions, which have been obtained using various spectroscopic methods. From these experiments we will conclude that, depending on the radii of the ions in the host alkaline earth fluoride crystal and the trivalent impurities the defect structure varies significantly. In some solid solutions evidence for appreciable preferential clustering has been found. On the other hand there is substantial evidence that for some other materials there is little or no preference towards clustering for impurity concentrations upto even a few mol%; here, the defect structure is determined more or less by statistics.

Hartog, H. W. Den

416

An Analytical Solution for Transient Thermal Response of an Insulated Structure  

NASA Technical Reports Server (NTRS)

An analytical solution was derived for the transient response of an insulated aerospace vehicle structure subjected to a simplified heat pulse. This simplified problem approximates the thermal response of a thermal protection system of an atmospheric entry vehicle. The exact analytical solution is solely a function of two non-dimensional parameters. A simpler function of these two parameters was developed to approximate the maximum structural temperature over a wide range of parameter values. Techniques were developed to choose constant, effective properties to represent the relevant temperature and pressure-dependent properties for the insulator and structure. A technique was also developed to map a time-varying surface temperature history to an equivalent square heat pulse. Using these techniques, the maximum structural temperature rise was calculated using the analytical solutions and shown to typically agree with finite element simulations within 10 to 20 percent over the relevant range of parameters studied.

Blosser, Max L.

2012-01-01

417

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

418

Structure and Interactions in Concentrated Diblock Copolymer Solutions  

NASA Astrophysics Data System (ADS)

We report on investigations of polystyrene/polyisoprene (PS/PI) diblock copolymers suspended in decane using small angle scattering techniques. The primary objective of this research is the understanding of the bulk properties and structure in concentrated diblock copolymers in a solvent selective for one block. In this case, decane is a good solvent for polyisoprene. Suspending PS/PI diblocks in decane at low concentrations produces monodisperse, spherical micelles comprising a dense core of polystyrene and a diffuse corona of polyisoprene. These micelles are well idealized as spherical cores with a fixed number of polyisoprene chains tethered to the surface. Since the local curvature plays an important role in determining the coronal density profile, the core radius and aggregation number are experimentally calculated. This experimental characterization lends each polymeric micelle to a description of the micellar architecture and pair-interaction potential through use of self-consistent mean field equations for tethered-chain systems. We use these pair-potentials to describe the liquid-like interference and disorder-order transition observed experimentally. Gillan's method, subject to a Rogers-Young closure, provides a description of the liquid-state. Density functional theory, specifically the modified weighted density approximation of Denton and Ashcroft, is used to estimate the solid-state. We supplement these calculations with a semi-quantitative phase diagram demonstrating the diversity in phase behavior resulting from tuning the range of the repulsions by varying block asymmetry; the phase diagram includes regions of face-centered cubic (FCC) and body-centered cubic (BCC) crystals depending on the range of the coronal layer thickness relative to the core dimension. In addition to these studies, we conclude with a discussion of the phase behavior of diblock copolymers at concentrations intermediate to those witnessing cubic micellar crystals and the ordered melt morphology; a region where shape transitions are anticipated. We find a curious mechanism for these transitions that first includes the melting of the micellar crystal. We present a qualitative argument for this order-disorder transition upon increasing the polymer concentration that focuses on a loss of the osmotic pressure gradient.

McConnell, Glen A.

419

The structure and dynamics in solution of Cu(I) pseudoazurin from Paracoccus pantotrophus.  

PubMed Central

The solution structure and backbone dynamics of Cu(I) pseudoazurin, a 123 amino acid electron transfer protein from Paracoccus pantotrophus, have been determined using NMR methods. The structure was calculated to high precision, with a backbone RMS deviation for secondary structure elements of 0.35+/-0.06 A, using 1,498 distance and 55 torsion angle constraints. The protein has a double-wound Greek-key fold with two alpha-helices toward its C-terminus, similar to that of its oxidized counterpart determined by X-ray crystallography. Comparison of the Cu(I) solution structure with the X-ray structure of the Cu(II) protein shows only small differences in the positions of some of the secondary structure elements. Order parameters S2, measured for amide nitrogens, indicate that the backbone of the protein is rigid on the picosecond to nanosecond timescale.

Thompson, G. S.; Leung, Y. C.; Ferguson, S. J.; Radford, S. E.; Redfield, C.

2000-01-01

420

The structure and dynamics in solution of Cu(I) pseudoazurin from Paracoccus pantotrophus.  

PubMed

The solution structure and backbone dynamics of Cu(I) pseudoazurin, a 123 amino acid electron transfer protein from Paracoccus pantotrophus, have been determined using NMR methods. The structure was calculated to high precision, with a backbone RMS deviation for secondary structure elements of 0.35+/-0.06 A, using 1,498 distance and 55 torsion angle constraints. The protein has a double-wound Greek-key fold with two alpha-helices toward its C-terminus, similar to that of its oxidized counterpart determined by X-ray crystallography. Comparison of the Cu(I) solution structure with the X-ray structure of the Cu(II) protein shows only small differences in the positions of some of the secondary structure elements. Order parameters S2, measured for amide nitrogens, indicate that the backbone of the protein is rigid on the picosecond to nanosecond timescale. PMID:10850794

Thompson, G S; Leung, Y C; Ferguson, S J; Radford, S E; Redfield, C

2000-05-01

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