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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

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

SciTech Connect

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

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

2009-01-01

3

Theory of Dilute Macromolecular Solutions  

Microsoft Academic Search

The object of this paper is to lay the foundations of the Theory of Dilute Macromolecular Solutions in a unified, simplified, and yet rigorous manner. It also aims to acquaint chemists and physicists with a field of rapidly\\u000a increasing significance, in view of possible applications to biophysics (and biochemistry). The Introduction gives a brief\\u000a outline of the historical development of

A. Isihara; E. Guth

4

Improved Fitting of Solution X-ray Scattering Data to Macromolecular Structures and Structural Ensembles by Explicit Water Modeling  

PubMed Central

A new procedure, AXES, is introduced for fitting small-angle X-ray scattering (SAXS) data to macromolecular structures and ensembles of structures. By using explicit water models to account for the effect of solvent, and by restricting the adjustable fitting parameters to those that dominate experimental uncertainties, including sample/buffer rescaling, detector dark current, and, within a narrow range, hydration layer density, superior fits between experimental high resolution structures and SAXS data are obtained. AXES results are found to be more discriminating than standard Crysol fitting of SAXS data when evaluating poorly or incorrectly modeled protein structures. AXES results for ensembles of structures previously generated for ubiquitin show improved fits over fitting of the individual members of these ensembles, indicating these ensembles capture the dynamic behavior of proteins in solution.

2010-01-01

5

Improved Fitting of Solution X-ray Scattering Data to Macromolecular Structures and Structural Ensembles by Explicit Water Modeling  

SciTech Connect

A new procedure, AXES, is introduced for fitting small-angle X-ray scattering (SAXS) data to macromolecular structures and ensembles of structures. By using explicit water models to account for the effect of solvent, and by restricting the adjustable fitting parameters to those that dominate experimental uncertainties, including sample/buffer rescaling, detector dark current, and, within a narrow range, hydration layer density, superior fits between experimental high resolution structures and SAXS data are obtained. AXES results are found to be more discriminating than standard Crysol fitting of SAXS data when evaluating poorly or incorrectly modeled protein structures. AXES results for ensembles of structures previously generated for ubiquitin show improved fits over fitting of the individual members of these ensembles, indicating these ensembles capture the dynamic behavior of proteins in solution.

Grishaev, Alexander; Guo, Liang; Irving, Thomas; Bax, Ad (IIT); (NIH)

2010-12-07

6

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

NASA Astrophysics Data System (ADS)

We report on measurements performed by Raman scattering and NMR technique on Poly(Ethylene Oxide) solutions both in H2O and D2O, at different concentration and temperature values. The Raman analysis of the D-LAM spectral contribution of PEO/H2O solutions reveals a frequency increase towards values corresponding to the crystal ones and a sharpening of the D-LAM band. Such evidences indicate that the addition of water destroys the intermolecular interactions and stiffens the coil structure, giving rise to a more ordered conformation with respect to that of the melt phase. Concerning the case of PEO/D2O solutions, notwithstanding the similar behaviour, one observes that the centre frequency and the width of the D-LAM contribution never approach the value obtained in the case of PEO/H2O, confirming the presence of a remarkable higher degree of disorder. Finally, the temperature analysis of the Raman D-LAM band in PEO/H2O and PEO/D2O mixtures, and of the hydrodynamic radius evaluated by NMR in PEO/D2O solutions reveals that the solvent power of water increases up to T=318 K decreasing at higher temperature in H2O, whereas in D2O shows a maximum at T=298 K. The present study shows that Raman scattering and NMR technique represent good tools for characterizing the structural properties of polymers in solution. The experimentally well-ascertained phenomenon reported here provides evidences of different temperature behaviours for PEO in H2O and D2O. What conclusively emerges is that isotopic substitution (notably hydrogen/deuterium) widely employed in many fields for manipulating the contrast while perturbing conformational and thermodynamical properties minimally, is, in some cases, open to criticism.

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

1999-10-01

7

Macromolecular complexes in crystals and solutions  

PubMed Central

This paper presents a discussion of existing methods for the analysis of macromolecular interactions and complexes in crystal packing. Typical situations and conditions where wrong answers may be obtained in the course of ordinary procedures are presented and discussed. The more general question of what the relationship is between natural (in-solvent) and crystallized assemblies is discussed and researched. A computational analysis suggests that weak interactions with K d ? 100?µM have a considerable chance of being lost during the course of crystallization. In such instances, crystal packing misrepresents macromolecular complexes and interactions. For as many as 20% of protein dimers in the PDB the likelihood of misrepresentation is estimated to be higher than 50%. Given that weak macromolecular interactions play an important role in many biochemical processes, these results suggest that a complementary noncrystallographic study should be always conducted when inferring structural aspects of weakly bound complexes.

Krissinel, Evgeny

2011-01-01

8

A General Method for Modeling Macromolecular Shape in Solution  

PubMed Central

A general method for modeling macromolecular shape in solution is described involving measurements of viscosity, radius of gyration, and the second thermodynamic virial coefficient. The method, which should be relatively straightforward to apply, does not suffer from uniqueness problems, involves shape functions that are independent of hydration, and models the gross conformation of the macromolecule in solution as a general triaxial ellipsoid. The method is illustrated by application to myosin, and the relevance and applicability of ellipsoid modeling to biological structures is discussed.

Harding, Stephen E.

1987-01-01

9

Grammatical representations of macromolecular structure.  

PubMed

Since the first application of context-free grammars to RNA secondary structures in 1988, many researchers have used both ad hoc and formal methods from computational linguistics to model RNA and protein structure. We show how nearly all of these methods are based on the same core principles and can be converted into equivalent approaches in the framework of tree-adjoining grammars and related formalisms. We also propose some new approaches that extend these core principles in novel ways. PMID:16796552

Chiang, David; Joshi, Aravind K; Searls, David B

2006-06-01

10

The Phenix Software for Automated Determination of Macromolecular Structures  

PubMed Central

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

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

2011-01-01

11

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

12

A new principle for macromolecular structure determination  

NASA Astrophysics Data System (ADS)

Protein NMR spectroscopy is a modern experimental technique for elucidating the three-dimensional structure of biological macromolecules in solution. From the data-analytical point of view, structure determination has always been considered an optimisation problem: much effort has been spent on the development of minimisation strategies; the underlying rationale, however, has not been revised. Conceptual difficulties with this approach arise since experiments only provide incomplete structural information: structure determination is an inference problem and demands for a probabilistic treatment. In order to generate realistic conformations, strong prior assumptions about physical interactions are indispensable. These interactions impose a complex structure on the posterior distribution making simulation of such models particularly difficult. We demonstrate, that posterior sampling is feasible using a combination of multiple Markov Chain Monte Carlo techniques. We apply the methodology to a sparse data set obtained from a perdeuterated sample of the Fyn SH3 domain.

Habeck, Michael; Rieping, Wolfgang; Nilges, Michael

2004-04-01

13

Validation of macromolecular flexibility in solution by small-angle X-ray scattering (SAXS).  

PubMed

The dynamics of macromolecular conformations are critical to the action of cellular networks. Solution X-ray scattering studies, in combination with macromolecular X-ray crystallography (MX) and nuclear magnetic resonance (NMR), strive to determine complete and accurate states of macromolecules, providing novel insights describing allosteric mechanisms, supramolecular complexes, and dynamic molecular machines. This review addresses theoretical and practical concepts, concerns, and considerations for using these techniques in conjunction with computational methods to productively combine solution-scattering data with high-resolution structures. I discuss the principal means of direct identification of macromolecular flexibility from SAXS data followed by critical concerns about the methods used to calculate theoretical SAXS profiles from high-resolution structures. The SAXS profile is a direct interrogation of the thermodynamic ensemble and techniques such as, for example, minimal ensemble search (MES), enhance interpretation of SAXS experiments by describing the SAXS profiles as population-weighted thermodynamic ensembles. I discuss recent developments in computational techniques used for conformational sampling, and how these techniques provide a basis for assessing the level of the flexibility within a sample. Although these approaches sacrifice atomic detail, the knowledge gained from ensemble analysis is often appropriate for developing hypotheses and guiding biochemical experiments. Examples of the use of SAXS and combined approaches with X-ray crystallography, NMR, and computational methods to characterize dynamic assemblies are presented. PMID:22639100

Hammel, Michal

2012-05-26

14

Cryo-Electron Tomography for Structural Characterization of Macromolecular Complexes  

PubMed Central

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

Cope, Julia; Heumann, John; Hoenger, Andreas

2011-01-01

15

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

16

Macromolecular Structure Database. Final Progress Report  

SciTech Connect

The central activity of the PDB continues to be the collection, archiving and distribution of high quality structural data to the scientific community on a timely basis. In support of these activities NIST has continued its roles in developing the physical archive, in developing data uniformity, in dealing with NMR issues and in the distribution of PDB data through CD-ROMs. The physical archive holdings have been organized, inventoried, and a database has been created to facilitate their use. Data from individual PDB entries have been annotated to produce uniform values improving tremendously the accuracy of results of queries. Working with the NMR community we have established data items specific for NMR that will be included in new entries and facilitate data deposition. The PDB CD-ROM production has continued on a quarterly basis, and new products are being distributed.

Gilliland, Gary L.

2003-09-23

17

Weighting of experimental evidence in macromolecular structure determination  

PubMed Central

The determination of macromolecular structures requires weighting of experimental evidence relative to prior physical information. Although it can critically affect the quality of the calculated structures, experimental data are routinely weighted on an empirical basis. At present, cross-validation is the most rigorous method to determine the best weight. We describe a general method to adaptively weight experimental data in the course of structure calculation. It is further shown that the necessity to define weights for the data can be completely alleviated. We demonstrate the method on a structure calculation from NMR data and find that the resulting structures are optimal in terms of accuracy and structural quality. Our method is devoid of the bias imposed by an empirical choice of the weight and has some advantages over estimating the weight by cross-validation.

Habeck, Michael; Rieping, Wolfgang; Nilges, Michael

2006-01-01

18

Macromolecular structure analysis and effective liquefaction pretreatment. Final report  

SciTech Connect

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

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

1994-07-01

19

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

20

Macromolecular structure of low rank coals and lignites  

SciTech Connect

The goal of this work was to learn more about the macromolecular structure of low rank coals and lignites. Our goal was to explore both covalent and non-covalent interactions in these coals. The work accomplished can be divided into four parts: (1) solvent swelling studies; (2) FTIR studies of hydrogen bonding; (3) the reactivity of free radicals in coals; and (4) IR studies of the glass-to-rubber transition of coals. Essentially all of our work in the first of these areas, solvent swelling studies, has been published and that paper is Appendix A. Only a portion of our studies in the other areas has been published. The papers are contained in this report as Appendices. The unpublished work is contained in three sections.

Larsen, J.W.; Flowers, R.A. II; Shawver, S.

1989-11-30

21

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

NASA Astrophysics Data System (ADS)

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 new 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.

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

2010-10-01

22

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

23

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

24

Protonate3D: Assignment of ionization states and hydrogen coordinates to macromolecular structures  

PubMed Central

A new method, called Protonate3D, is presented for the automated prediction of hydrogen coordinates given the 3D coordinates of the heavy atoms of a macromolecular structure. Protonate3D considers side-chain “flip,” rotamer, tautomer, and ionization states of all chemical groups, ligands, and solvent, provided suitable templates are available in a parameter file. The energy model includes van der Waals, Coulomb, solvation, rotamer, tautomer, and titration effects. The results of computational validation experiments suggest that Protonate3D can accurately predict the location of hydrogen atoms in macromolecular structures. Proteins 2009. © 2008 Wiley-Liss, Inc.

Labute, Paul

2009-01-01

25

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

26

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

PubMed

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(N(3)) 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. PMID:24089734

Ando, Tadashi; Chow, Edmond; Skolnick, Jeffrey

2013-09-28

27

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

28

Macromolecular structure of low rank coals and lignites. Final report, August 1, 1984-April 1, 1989.  

National Technical Information Service (NTIS)

The goal of this work was to learn more about the macromolecular structure of low rank coals and lignites. Our goal was to explore both covalent and non-covalent interactions in these coals. The work accomplished can be divided into four parts: (1) solven...

J. W. Larsen R. A. Flowers S. Shawver

1989-01-01

29

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

30

Quantification of Complex Topologies in Macromolecular and Nanoscale Structures using Small-Angle Scattering  

NASA Astrophysics Data System (ADS)

Polymers are characterized by molecular weight distribution, tacticity, block copolymer content and branch content and chain topology. The branch structure and particularly the topology of branched chains has remained a difficult characterization problem. Recently we have developed a scaling model that can be coupled with small-angle scattering to measure the average branch length, number of branches and branch-on-branch structure in macromolecules of complex topology. This method has been extended to understand the structure of two dimensional structures and crumpling in these macromolecular systems. We have explored a wide range of materials in this regard. This poster will give an overview of the current uses for the scaling model for macromolecular topology. References pertaining to this poster can be found at http://www.eng.uc.edu/˜gbeaucag/BranchingPapers.html.

Pradhan, Siddharth; Ramachandran, Ramanth; Rai, Durgesh; Beaucage, Gregory

2012-02-01

31

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

32

Architecture of macromolecular network of soft functional materials: from structure to function.  

PubMed

An enhanced macromolecular nanofiber network and its implications have been developed by employing the understanding of its formation with an emphasis on its topological aspect. Using agarose aqueous solution as a typical example, the macromolecular nanofiber network of soft functional materials has been clearly visualized for the first time using the developed technique of field emission scanning electronic microscopy coupled with flash-freeze-drying. Both the systematic kinetic study and the image evidence indicates that the nanofiber network in soft functional materials such as agarose turns out to form through a self-expitaxial nucleation-controlled process. This new understanding enables us to engineer ultra functions of soft materials via nanofiber network architecture, which in turn opens up a new direction in nano fabrication. PMID:17472367

Xiong, Jun-Ying; Liu, Xiang-Yang; Li, Jing-Liang; Vallon, Martin Wilhelm

2007-05-02

33

MACROMOLECULAR NETWORK STRUCTURE OF COALS: INTERPRETATION OF EQUILIBRIUM AND DYNAMIC SWELLING EXPERIMENTS  

Microsoft Academic Search

The macromolecular structures of twenty-one coals were investigated via equilibrium and dynamic solvent swelling experiments. The variables were the carbon content of the coal sample, ranging from 69 to 94%C (dmmf); the solvent used, including pyridine, methanol, ethanol, n-propanol, 2-butanone, acetone, and cyclohexane; the size of the coal particles, which were 1-2 cm('3) sections, 20-30 mesh, 50-60 mesh and 80-100

LUCY MARIE HAIR LUCHT; L. M. H

1983-01-01

34

The chemical structure of macromolecular fractions of a sulfur-rich oil  

SciTech Connect

A selective stepwise chemical degradation has been developed for structural studies of high-molecular-weight (HMW) fractions of sulfur-rich oils. The degradation steps are: (i) desulfurization; (ii) cleavage of oxygen-carbon bonds; and (iii) oxidation of aromatic structural units. After each step, the remaining macromolecular matter was subjected to the subsequent reaction. This degradation scheme was applied to the asphaltene, the resin, and a macromolecular fraction of low polarity (LPMF) of Rozel Point oil. Total amounts of degraded low-molecular-weight compounds increased progressively in the order asphaltene < resin < LPMF. Desulfurization yielded mainly phytane, steranes, and triterpanes. Oxygen-carbon bond cleavage resulted in hydrocarbon fractions predominated by n-alkanes and acyclic isoprenoids. The oxidation step afforded high amounts of linear carboxylic acids in the range of C[sub 11] to C[sub 33]. The released compounds provide a more complete picture of the molecular structure of the oil fractions than previously available. Labelling experiments with deuterium atoms allowed characterization of the site of bonding and the type of linkage for compounds. Evidence is presented that subunits of the macromolecular network are attached simultaneously by oxygen and sulfur (n-alkanes, hopanes) or by sulfur and aromatic units (n-alkanes, steranes).

Richnow, H.H.; Jenisch, A.; Michaelis, W. (Universitaet Hamburg (Germany))

1993-06-01

35

Integrative Structure Modeling of Macromolecular Assemblies from Proteomics Data*  

PubMed Central

Proteomics techniques have been used to generate comprehensive lists of protein interactions in a number of species. However, relatively little is known about how these interactions result in functional multiprotein complexes. This gap can be bridged by combining data from proteomics experiments with data from established structure determination techniques. Correspondingly, integrative computational methods are being developed to provide descriptions of protein complexes at varying levels of accuracy and resolution, ranging from complex compositions to detailed atomic structures.

Lasker, Keren; Phillips, Jeremy L.; Russel, Daniel; Velazquez-Muriel, Javier; Schneidman-Duhovny, Dina; Tjioe, Elina; Webb, Ben; Schlessinger, Avner; Sali, Andrej

2010-01-01

36

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

37

Macromolecular structure determination in the post-genome era  

NASA Astrophysics Data System (ADS)

Recent advances in genetics, molecular biology and crystallographic instrumentation and methodology have led to a revolution in the field of Structural Molecular Biology (SMB). These combined advances have paved the way to a more complete and detailed understanding of the biological macromolecules that make up an organism, both in terms of their individual functions and also the interactions between them. In this paper we describe a large-scale, genomic approach to the three-dimensional structure determination of macromolecules and their complexes, using high-throughput methodology to streamline all aspects of the process. This task requires the development of automated high-intensity synchrotron beam lines for X-ray diffraction data collection from single crystal samples. Furthermore, these beam lines must be operated within a sophisticated software and hardware environment, which is capable of delivering a completely automated structure determination pipeline. The SMB resource at SSRL is developing a system for the structure determination steps of this process, starting with the initial characterization of the frozen sample, followed by data collection, data reduction, phase determination, and model building. This paper focuses on the data collection elements of this high-throughput system.

Kuhn, P.; Soltis, S. M.

2001-07-01

38

Determining macromolecular assembly structures by molecular docking and fitting into an electron density map  

PubMed Central

Structural models of macromolecular assemblies are instrumental for gaining a mechanistic understanding of cellular processes. Determining these structures is a major challenge for experimental techniques, such as X-ray crystallography, NMR spectroscopy and electron microscopy. Thus, computational modeling techniques, including molecular docking, are required. The development of most molecular docking methods has so far been focused on modeling of binary complexes. We have recently introduced the MultiFit method for modeling the structure of a multi-subunit complex by simultaneously optimizing the fit of the model into an electron microscopy density map of the entire complex and the shape complementarity between interacting subunits. Here, we report algorithmic advances of the MultiFit method that result in an efficient and accurate assembly of the input subunits into their density map. The successful predictions and the increasing number of complexes being characterized by electron microscopy suggests that the CAPRI challenge could be extended to include docking-based modeling of macromolecular assemblies guided by electron microscopy.

Lasker, Keren; Sali, Andrej; Wolfson, Haim J.

2010-01-01

39

Automated Structure Solution with the PHENIX Suite  

SciTech Connect

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

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

2008-06-09

40

Automation of macromolecular crystallography beamlines.  

PubMed

The production of three-dimensional crystallographic structural information of macromolecules can now be thought of as a pipeline which is being streamlined at every stage from protein cloning, expression and purification, through crystallisation to data collection and structure solution. Synchrotron X-ray beamlines are a key section of this pipeline as it is at these that the X-ray diffraction data that ultimately leads to the elucidation of macromolecular structures are collected. The burgeoning number of macromolecular crystallography (MX) beamlines available worldwide may be enhanced significantly with the automation of both their operation and of the experiments carried out on them. This paper reviews the current situation and provides a glimpse of how a MX beamline may look in the not too distant future. PMID:15910915

Arzt, Steffi; Beteva, Antonia; Cipriani, Florent; Delageniere, Solange; Felisaz, Franck; Förstner, Gabriele; Gordon, Elspeth; Launer, Ludovic; Lavault, Bernard; Leonard, Gordon; Mairs, Trevor; McCarthy, Andrew; McCarthy, Joanne; McSweeney, Sean; Meyer, Jens; Mitchell, Edward; Monaco, Stephanie; Nurizzo, Didier; Ravelli, Raimond; Rey, Vicente; Shepard, William; Spruce, Darren; Svensson, Olof; Theveneau, Pascal

2005-10-01

41

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

42

Filter diagonalization method-based mass spectrometry for molecular and macromolecular structure analysis.  

PubMed

Molecular and macromolecular structure analysis by high resolution and accurate mass spectrometry (MS) is indispensable for a number of fundamental and applied research areas, including health and energy domains. Comprehensive structure analysis of molecules and macromolecules present in the extremely complex samples and performed under time-constrained experimental conditions demands a substantial increase in the acquisition speed of high resolution MS data. We demonstrate here that signal processing based on the filter diagonalization method (FDM) provides the required resolution for shorter experimental transient signals in ion cyclotron resonance (ICR) MS compared to the Fourier transform (FT) processing. We thus present the development of a FDM-based MS (FDM MS) and demonstrate its implementation in ICR MS. The considered FDM MS applications are in bottom-up and top-down proteomics, metabolomics, and petroleomics. PMID:22376180

Kozhinov, Anton N; Tsybin, Yury O

2012-03-08

43

Bonding of Macromolecular Hydrogels Using Perturbants  

PubMed Central

This work describes a method to bond patterned macromolecular gels into monolithic structures using perturbants. Bonding strengths for a variety of solutes follow a Hofmeister ordering; this result and optical measurements indicate that bonding occurs by reversible perturbation of contacting gels. The resulting microfluidic gels are mechanically robust and can serve as scaffolds for cell culture.

Price, Gavrielle M.; Chu, Kengyeh K.; Truslow, James G.; Tang-Schomer, Min D.; Golden, Andrew P.; Mertz, Jerome; Tien, Joe

2008-01-01

44

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

45

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

2013-09-20

46

Mechanism of helix induction in poly(4-carboxyphenyl isocyanide) with chiral amines and memory of the macromolecular helicity and its helical structures.  

PubMed

An optically inactive poly(4-carboxyphenyl isocyanide) (poly-1-H) changed its structure into the prevailing, one-handed helical structure upon complexation with optically active amines in dimethylsulfoxide (DMSO) and water, and the complexes show a characteristic induced circular dichroism in the polymer backbone region. Moreover, the macromolecular helicity induced in water and aqueous organic solutions containing more than 50 vol % water could be "memorized" even after complete removal of the chiral amines (h-poly-1b-H), while that induced in DMSO and DMSO-water mixtures containing less than 30 vol % water could not maintain the optical activity after removal of the chiral amines (poly-1a-H). We now report fully detailed studies of the helix induction mechanism with chiral amines and the memory of the macromolecular helicity in water and a DMSO-water mixture by various spectroscopic measurements, theoretical calculations, and persistence length measurements together with X-ray diffraction (XRD) measurements. From the spectroscopic results, such as circular dichroism (CD), absorption, IR, vibrational CD, and NMR of poly-1a-H, h-poly-1b-H, and original poly-1-H, we concluded that the specific configurational isomerization around the C horizontal lineN double bonds occurs during the helicity induction process in each solvent. In order to obtain the structural information, XRD measurements were done on the uniaxially oriented films of the corresponding methyl esters (poly-1-Me, poly-1a-Me, and h-poly-1b-Me) prepared from their liquid crystalline polymer solutions. On the basis of the XRD analyses, the most plausible helical structure of poly-1a-Me was proposed to be a 9-unit/5-turn helix with two monomer units as a repeating unit, and that of h-poly-1b-Me was proposed to be a 10-unit/3-turn helix consisting of one repeating monomer unit. The density functional theory calculations of poly(phenyl isocyanide), a model polymer of h-poly-1b-Me, afforded a 7-unit/2-turn helix as the most possible helical structure, which is in good agreement with the XRD results. Furthermore, the persistence length measurements revealed that these structural changes accompany a significant change in the main-chain stiffness. The mechanism of helix induction in poly-1-H and the memory of the macromolecular helicity are discussed on the basis of these results. PMID:19580322

Hase, Yoko; Nagai, Kanji; Iida, Hiroki; Maeda, Katsuhiro; Ochi, Noriaki; Sawabe, Kyoichi; Sakajiri, Koichi; Okoshi, Kento; Yashima, Eiji

2009-08-01

47

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

48

Macromolecular Modeling with Rosetta  

Microsoft Academic Search

Advances over the past few years have begun to enable prediction and design of macromolecular structures at near-atomic accuracy. Progress has stemmed from the development of reasonably accurate and efficiently computed all-atom potential functions as well as effec- tive conformational sampling strategies appropriate for searching a highly rugged energy landscape, both driven by feedback from struc- ture prediction and design

Rhiju Das; David Baker

2008-01-01

49

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

50

Self-consistent colloidal energy and diffusivity landscapes in macromolecular solutions.  

PubMed

We report a dynamic analysis to simultaneously measure colloidal forces and hydrodynamic interactions in the presence of both adsorbed and unadsorbed macromolecules. A Bayesian inference method is used to self-consistently obtain the position-dependent potential energy (i.e., energy landscape) and diffusivity (i.e., diffusivity landscape) from measured colloidal trajectories normal to a wall. Measurements are performed for particles and surfaces with adsorbed polyethylene oxide (PEO) copolymer as a function of unadsorbed PEO homopolymer concentration. Energy landscapes are well described by a steric repulsion between adsorbed brushes and depletion attraction due to unadsorbed macromolecules. Diffusivity landscapes show agreement with predicted short-range permeable brush models and long-range mobilities determined by the bulk solution viscosity. Lower than expected mobilities in the vicinity of overlapping depletion layers are attributed to interactions of adsorbed and unadsorbed macromolecules altering nonconservative lubrication forces. PMID:24067114

Beltran-Villegas, Daniel J; Edwards, Tara D; Bevan, Michael A

2013-09-27

51

Tubular microporous alumina structure for demulsifying vegetable oil\\/water emulsions and concentrating macromolecular suspensions  

Microsoft Academic Search

A microstructure composed of alumina–silica (mullite, 3Al2O3·2SiO2) was molded into tubes to be used in a microfiltration process for separating water\\/vegetable oil emulsions and to concentrate macromolecular suspensions. The microporous tubes were produced by the precipitation method using raw material supplied by Rhodia do Brasil Ltda, and sintered at a final temperature of 1450°C. The microporous medium was characterized by

Sérgio R. Fontes; Viviane M. Silva Queiroz; Elson Longo; Marcus V. Antunes

2005-01-01

52

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

PubMed

Because understanding the structure of biological macromolecules is critical to understanding their function, students of biochemistry should become familiar not only with viewing, but also with generating and manipulating structural representations. We report a strategy from a one-semester undergraduate biochemistry course to integrate use of structural representation tools into both laboratory and homework activities. First, early in the course we introduce the use of readily available open-source software for visualizing protein structure, coincident with modules on amino acid and peptide bond properties. Second, we use these same software tools in lectures and incorporate images and other structure representations in homework tasks. Third, we require a capstone project in which teams of students examine a protein-nucleic acid complex and then use the software tools to illustrate for their classmates the salient features of the structure, relating how the structure helps explain biological function. To ensure engagement with a range of software and database features, we generated a detailed template file that can be used to explore any structure, and that guides students through specific applications of many of the software tools. In presentations, students demonstrate that they are successfully interpreting structural information, and using representations to illustrate particular points relevant to function. Thus, over the semester students integrate information about structural features of biological macromolecules into the larger discussion of the chemical basis of function. Together these assignments provide an accessible introduction to structural representation tools, allowing students to add these methods to their biochemical toolboxes early in their scientific development. © 2013 by The International Union of Biochemistry and Molecular Biology, 41(5):351-359, 2013. PMID:24019219

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

2013-09-10

53

The First Crystal Structure of a Macromolecular Assembly under High Pressure: CpMV at 330 MPa  

PubMed Central

The structure of cubic Cowpea mosaic virus crystals, compressed at 330 MPa in a diamond anvil cell, was refined at 2.8 Å from data collected using ultrashort-wavelength (0.331 Å) synchrotron radiation. With respect to the structure at atmospheric pressure, order is increased with lower Debye Waller factors and a larger number of ordered water molecules. Hydrogen-bond lengths are on average shorter and the cavity volume is strongly reduced. A tentative mechanistic explanation is given for the coexistence of disordered and ordered cubic crystals in crystallization drops and for the disorder-order transition observed in disordered crystals submitted to high pressure. Based on such explanation, it can be concluded that pressure would in general improve, albeit to a variable extent, the order in macromolecular crystals.

Girard, Eric; Kahn, Richard; Mezouar, Mohamed; Dhaussy, Anne-Claire; Lin, Tianwei; Johnson, John E.; Fourme, Roger

2005-01-01

54

The Contribution of Macromolecular Structure to the Retention of LDL at Arterial Branch Points  

PubMed Central

Background Extracellular deposition of low-density lipoproteins (LDL) in the arterial wall is an essential early step in atherosclerosis. This process preferentially occurs at arterial branch points, reflecting a regional variation in lipoprotein-arterial wall interactions. In this study, we characterized the sub-micron microstructure of arterial wall collagen and elastin to evaluate its potential role in regional LDL deposition. Methods and Results Using two-photon microscopy, the intrinsic optical properties of collagen and elastin were utilized to determine the arterial wall macromolecular microstructure in fresh porcine and murine arteries. This optical approach generated unique non-destructive en face three-dimensional views of the wall. The collagen/elastin microstructure was found to vary with the topology of the arterial bed. A nearly confluent elastin surface layer was present throughout, but was missing at atherosclerosis-susceptible branch points, exposing dense collagen-proteoglycan complexes. In LDL binding studies, this luminal elastin layer limited LDL penetration while its absence at the branches resulted in extensive LDL binding. Furthermore, LDL co-localized with proteoglycans with a sigmoidal dose dependence (inflection point ~130 mg LDL/dL). Ionic strength and competing anions studies were consistent with the initial interaction of LDL with proteoglycans to be electrostatic in nature. Conclusions This optical sectioning approach provided a robust three-dimensional collagen/elastin microstructure of the arterial wall in fresh samples. At atherosclerosis-susceptible vascular branch points, the absence of a luminal elastin barrier and presence of a dense collagen/proteoglycan matrix contributes to increased retention of LDL.

Kwon, Gina P.; Schroeder, Jamie L.; Amar, Marcelo J.; Remaley, Alan T.; Balaban, Robert S.

2009-01-01

55

O the Phase Refinement and Extension of Macromolecular Structures Using both Real and Reciprocal Space Approaches  

NASA Astrophysics Data System (ADS)

Available from UMI in association with The British Library. By examining the solution to the phase problem of X-ray crystallography, it is established that the structure factor magnitudes and phases are linked through constraints on the electron density. There are real and reciprocal space approaches to the phase problem depending on the way the constraints on electron density are exploited. A constraint on the electron density--the correct density histogram--is added to the list of other constraints. A new density modification technique--histogram matching --was developed based on the matching of the density histogram to that of the correct one. Its application to 2Zn pig insulin successfully refined and extended the 1.9A MIR phases to 1.5A resolution. In order to obtain a molecular envelope with a detailed boundary, a molecular envelope refinement technique was designed which proved to be quite effective. A gradient technique of defining molecular boundary was also explored and was found to be better than the conventional convolution technique. The two dimensional histogram of density and gradient was examined. It was found that the matching of density histograms also matches that of the gradient histograms. The combination of Sayre's equation with solvent flattening and histogram matching led to a new phase refinement and extension technique--SQUASH. It proved to be a powerful technique by its successful refinement of 3.0A MIR phases of 2Zn pig insulin and subsequent extension to 2.0A resolution.

Zhang, Kam Yong Jian

56

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

57

Statistical mechanics of macromolecular complexation  

NASA Astrophysics Data System (ADS)

The self-assembly of macromolecules through molecular association has attracted long-standing attention in soft-condensed matter physics. The hierarchical formation from small-scale building blocks into larger-scale complex structures often leads to very rich phase behavior controlled by various ambient conditions. The understanding and control of the phase behavior of self-assembling systems require detailed knowledge about the entropy and enthalpy contributions to the free energy of the system. However, this knowledge is limited at the present time because a comprehensive theoretical description of molecular association is still lacking. In this thesis, four tales of achievements in developing theories of macromolecular complexation are presented. (1) We begin with an analytically solvable model of the self-assembly of rigid macromolecules with surface adsorption. A generic understanding of the driving force and the role of entropy is obtained from the exact solutions. (2) We move on to further development of the theory in order to study the complexation between polymers and ionic molecules. The extension of the first model to chain-like molecules is performed using a well-established method in polymer physics, the self-consistent field theory (SCFT) of polymers. We also discuss gelation in this system within the scope of mean-filed approximations. (3) Then, a ladder-like polymer-polymer complexation is studied. Unconventional phase diagrams are predicted from the modified SCFT, indicating a large effect of variations in entropy due to the complexation on bulk properties. (4) Finally, the kinetic aspect of macromolecular binding reactions is discussed.

Nakamura, Issei

58

Proteomic characterization of a triton-insoluble fraction from chloroplasts defines a novel group of proteins associated with macromolecular structures.  

PubMed

Proteomic analysis of a Triton X-100 insoluble, 30,000 x g pellet from purified pea chloroplasts resulted in the identification of 179 nonredundant proteins. This chloroplast fraction was mostly depleted of chloroplast membranes since only 23% and 9% of the identified proteins were also observed in envelope and thylakoid membranes, respectively. One of the most abundant proteins in this fraction was sulfite reductase, a dual function protein previously shown to act as a plastid DNA condensing protein. Approximately 35 other proteins known (or predicted) to be associated with high-density protein-nucleic acid particles (nucleoids) were also identified including a family of DNA gyrases, as well as proteins involved in plastid transcription and translation. Although nucleoids appeared to be the predominant component of 30k x g Triton-insoluble chloroplast preparations, multi-enzyme protein complexes were also present including each subunit to the pyruvate dehydrogenase and acetyl-CoA carboxylase multi-enzyme complexes, as well as a proposed assembly of the first three enzymes of the Calvin cycle. Approximately 18% of the proteins identified were annonated as unknown or hypothetical proteins and another 20% contained "putative" or "like" in the identifier tag. This is the first proteomic characterization of a membrane-depleted, high-density fraction from plastids and demonstrates the utility of this simple procedure to isolate intact macromolecular structures from purified organelles for analysis of protein-protein and protein-nucleic acid interactions. PMID:15822927

Phinney, Brett S; Thelen, Jay J

59

Structural Studies on Membrane Proteins and Biological Macromolecular Assemblies in Japan  

NASA Astrophysics Data System (ADS)

Structural studies on membrane proteins have been performed at atomic level by both three-dimensional X-ray crystallography and two-dimensional electron crystallography in Japan as in Europe and Unites States. More than 13 membrane protein structures were elucidate by X-ray method in our country, and seven membrane protein structures were determined by cryo-electron microscopic method developed by Fujiyoshi of Kyoto University. Extensive crystallographic studies on calcium pump and cytochrome c oxidase elucidated their functional mechanisms at atomic level. Structure and switching mechanism of a flagellum were studied by X-ray and electron microscopic methods. Vault structure exhibiting D39 symmetry was determined by X-ray method.

Tsukihara, Tomitake

60

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

61

GRASP2: visualization, surface properties, and electrostatics of macromolecular structures and sequences.  

PubMed

The widespread use of the original version of GRASP revealed the importance of the visualization of physicochemical and structural properties on the molecular surface. This chapter describes a new version of GRASP that contains many new capabilities. In terms of analysis tools, the most notable new features are sequence and structure analysis and alignment tools and the graphical integration of sequence and structural information. Not all the new GRASP2 could be described here and more capabilities are continually being added. An on-line manual, details on obtaining the software, and technical notes about the program and the Troll software library can be found at the Honig laboratory Web site (http://trantor.bioc.columbia.edu). PMID:14696386

Petrey, Donald; Honig, Barry

2003-01-01

62

Terminating a macromolecular helix. Structural model for the minor proteins of bacteriophage M13.  

PubMed

Analysis of the results of X-ray diffraction, electron microscopy and s sequence studies of filamentous bacteriophage M13 are used to construct structural models for the minor proteins gp7 and gp9 at the end of the virus assembled first, and a portion of gp6 at the end of the virus that binds host. Comparison of the sequence of the major coat protein, gp8, with those of gp7, gp9 and gp6 indicates that significant portions of these three proteins have sequences similar to that of gp8. Assuming that sequence similarity is indicative of structural similarity, gp7, gp9 and portions of gp6 are modeled based on what is known about the structure of gp8. These molecular models are analyzed to predict the packing of the minor proteins with the terminal gp8 proteins (the last gp8 proteins at either end of the helix). This analysis indicates that the gp8 proteins integrated into the virus first may have a structure distinct from those in the body of the virus particle. The gp8 proteins at the end assembled last appear to have a conformation very similar to that of the integral coat proteins. These models place specific constraints on models for the process of viral assembly. PMID:1469721

Makowski, L

1992-12-01

63

MolProbity: all-atom structure validation for macromolecular crystallography  

PubMed Central

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 be performed automatically in MolProbity and all of the diagnostics are presented in chart and graphical forms that help guide manual rebuilding. X-ray crystallography provides a wealth of biologically important molecular data in the form of atomic three-dimensional structures of proteins, nucleic acids and increasingly large complexes in multiple forms and states. Advances in automation, in everything from crystallization to data collection to phasing to model building to refinement, have made solving a structure using crystallo­graphy easier than ever. However, despite these improvements, local errors that can affect biological interpretation are widespread at low resolution and even high-resolution structures nearly all contain at least a few local errors such as Ramachandran outliers, flipped branched protein side chains and incorrect sugar puckers. It is critical both for the crystallographer and for the end user that there are easy and reliable methods to diagnose and correct these sorts of errors in structures. MolProbity is the authors’ contribution to helping solve this problem and this article reviews its general capabilities, reports on recent enhancements and usage, and presents evidence that the resulting improvements are now beneficially affecting the global database.

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

2010-01-01

64

MolProbity: all-atom structure validation for macromolecular crystallography.  

PubMed

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 be performed automatically in MolProbity and all of the diagnostics are presented in chart and graphical forms that help guide manual rebuilding. X-ray crystallography provides a wealth of biologically important molecular data in the form of atomic three-dimensional structures of proteins, nucleic acids and increasingly large complexes in multiple forms and states. Advances in automation, in everything from crystallization to data collection to phasing to model building to refinement, have made solving a structure using crystallography easier than ever. However, despite these improvements, local errors that can affect biological interpretation are widespread at low resolution and even high-resolution structures nearly all contain at least a few local errors such as Ramachandran outliers, flipped branched protein side chains and incorrect sugar puckers. It is critical both for the crystallographer and for the end user that there are easy and reliable methods to diagnose and correct these sorts of errors in structures. MolProbity is the authors' contribution to helping solve this problem and this article reviews its general capabilities, reports on recent enhancements and usage, and presents evidence that the resulting improvements are now beneficially affecting the global database. PMID:20057044

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

2009-12-21

65

Hydroxyl Radical Footprinting in vivo: Mapping Macromolecular Structures with Synchrotron Radiation  

SciTech Connect

We used a high flux synchrotron X-ray beam to map the structure of 16S rRNA and RNase P in viable bacteria in situ. A 300 ms exposure to the X-ray beam was sufficient for optimal cleavage of the phosphodiester backbone. The in vivo footprints of the 16S rRNA in frozen cells were similar to those obtained in vitro and were consistent with the predicted accessibility of the RNA backbone to hydroxyl radical. Protection or enhanced cleavage of certain nucleotides in vivo can be explained by interactions with tRNA and perturbation of the subunit interface. Thus, short exposures to a synchrotron X-ray beam can footprint the tertiary structure and protein contacts of RNA-protein complexes with nucleotide resolution in living cells.

Adilakshmi,T.; Lease, R.; Woodson, S.

2006-01-01

66

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

67

Relating Macromolecular Function and Association: The Structural Basis of Protein–DNA and RNA Recognition  

Microsoft Academic Search

The interaction between proteins and DNA or RNA plays an essential part in the function of biological macromolecules, and\\u000a its physical basis resides in the three-dimensional structure of the interfaces that they form. We analyze the geometric,\\u000a chemical and physical chemical properties of the interfaces that occur in sets of protein–DNA and protein–RNA complexes issued\\u000a from X-ray studies and deposited

Joël Janin; Ranjit P. Bahadur

2008-01-01

68

Three-dimensional structure of a macromolecular assembly that regulates type III secretion in Yersinia pestis.  

PubMed

Yersinia pestis, the causative agent of plague, utilizes a type III secretion system (T3SS) to inject effector proteins directly into the cytosol of mammalian cells where they interfere with signal transduction pathways that regulate actin cytoskeleton dynamics and inflammation, thereby enabling the bacterium to avoid engulfment and destruction by macrophages. Type III secretion normally does not occur in the absence of close contact with eukaryotic cells. Negative regulation is mediated in part by a multiprotein complex that has been proposed to act as a physical impediment to type III secretion by blocking the entrance to the secretion apparatus prior to contact with mammalian cells. This complex is composed of YopN, its heterodimeric secretion chaperone SycN-YscB, and TyeA. Here, we report two crystal structures of YopN in complex with its heterodimeric secretion chaperone SycN-YscB and the co-regulatory protein TyeA, respectively. By merging these two overlapping structures, it was possible to construct a credible theoretical model of the YopN-SycN-YscB-TyeA complex. The modeled assembly features the secretion signaling elements of YopN at one end of an elongated structure and the secretion regulating TyeA binding site at the other. A patch of highly conserved residues on the surface of the C-terminal alpha-helix of TyeA may mediate its interaction with structural components of the secretion apparatus. Conserved arginine residues that reside inside a prominent cavity at the dimer interface of SycN-YscB were mutated in order to investigate whether they play a role in targeting the YopN-chaperone complex to the type III secretion apparatus. One of the mutants exhibited a phenotype that is consistent with this hypothesis. PMID:15701523

Schubot, Florian D; Jackson, Michael W; Penrose, Kerri J; Cherry, Scott; Tropea, Joseph E; Plano, Gregory V; Waugh, David S

2005-01-20

69

Macromolecular chelation as an improved mechanism of protease inhibition: structure of the ecotin-trypsin complex.  

PubMed Central

The 2.4 A crystal structure (R = 0.180) of the serine protease inhibitor ecotin was determined in a complex with trypsin. Ecotin's dimer structure provides a second discrete and distal binding site for trypsin and, as shown by modelling experiments, other serine proteases. The second site is approximately 45 A from the reactive/active site of the complex and features 13 hydrogen bonds, including six that involve carbonyl oxygen atoms and four bridged by water molecules. Contacts ecotin makes with trypsin's active site are similar to, though more extensive than, those found between trypsin and basic pancreatic trypsin inhibitor. The side chain of ecotin Met84 is found in the substrate binding pocket of trypsin where it makes few contacts, but also does not disrupt the solvent structure or cause misalignment of the scissile bond. This first case of protein dimerization being used to augment binding energy and allow chelation of a target protein provides a new model for protein-protein interactions and for protease inhibition. Images

McGrath, M E; Erpel, T; Bystroff, C; Fletterick, R J

1994-01-01

70

Secondary Interactions Involving Zinc-Bound Ligands: Roles in Structural Stabilization and Macromolecular Interactions  

PubMed Central

A large number of proteins contain bound zinc ions. These zinc ions are frequently coordinated by a combination of histidine and cysteine residues. In addition to atoms that coordinate directly to the zinc ions, these side chains have groups that can donate or accept hydrogen bonds from other groups. These secondary interactions can help stabilize the zinc-binding sites, can contribute to protein folding and stability, and, on occasion, can participate in interactions with other macromolecules. Five examples of these secondary interactions are discussed: carbonic anhydrase (where secondary interactions involving histidine residues stabilize the zinc-binding site thermodynamically and kinetically), retroviral nucleocapsid proteins and TRAF proteins (where cysteinate sulfur to peptide NH hydrogen bonds contribute to the structural relationships between adjacent domains), and zinc finger proteins and TIS11 where secondary interactions participate in protein-nucleic acid interactions.

Namuswe, Frances; Berg, Jeremy M.

2012-01-01

71

Structure and property relations of macromolecular self-assemblies at interfaces  

NASA Astrophysics Data System (ADS)

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

Yang, Zhihao

72

Effects of macromolecular crowding on the structural stability of human ?-lactalbumin.  

PubMed

The folding of protein, an important process for protein to fulfill normal functions, takes place in crowded physiological environments. ?-Lactalbumin, as a model system for protein-folding studies, has been used extensively because it can form stable molten globule states under a range of conditions. Here we report that the crowding agents Ficoll 70, dextran 70, and polyethylene glycol (PEG) 2000 have different effects on the structural stability of human ?-lactalbumin (HLA) represented by the transition to a molten globule state: dextran 70 dramatically enhances the thermal stability of Ca(2+)-depleted HLA (apo-HLA) and Ficoll 70 enhances the thermal stability of apo-HLA to some extent, while PEG 2000 significantly decreases the thermal stability of apo-HLA. Ficoll 70 and dextran 70 have no obvious effects on trypsin degradation of apo-HLA but PEG 2000 accelerates apo-HLA degradation by trypsin and destabilizes the native conformation of apo-HLA. Furthermore, no interaction is observed between apo-HLA and Ficoll 70 or dextran 70, but a weak, non-specific interaction between the apo form of the protein and PEG 2000 is detected, and such a weak, non-specific interaction could overcome the excluded-volume effect of PEG 2000. Our data are consistent with the results of protein stability studies in cells and suggest that stabilizing excluded-volume effects of crowding agents can be ameliorated by non-specific interactions between proteins and crowders. PMID:22735492

Zhang, De-Lin; Wu, Ling-Jia; Chen, Jie; Liang, Yi

2012-06-26

73

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

PubMed

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

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

2012-09-02

74

C-H stretch for probing kinetics of self-assembly into macromolecular chiral structures at interfaces by chiral sum frequency generation spectroscopy.  

PubMed

Self-assembly of molecules into chiral macromolecular and supramolecular structures at interfaces is important in various fields, such as biomedicine, polymer sciences, material sciences, and supramolecular chemistry. However, probing the kinetics at interfaces remains challenging because it requires a real-time method that has selectivity to both interface and chirality. Here, we introduce an in situ approach of using the C-H stretch as a vibrational probe detected by chiral sum frequency generation spectroscopy (cSFG). We showed that the C-H stretch cSFG signals of an amphiphilic peptide (LK7?) can reveal the kinetics of its self-assembly into chiral ?-sheet structures at the air-water interface. The cSFG experiments in conjunction with measurements of surface pressure allow us to propose a mechanism of the self-assembly process, which involves an immediate adsorption of disordered structures followed by a lag phase before the self-assembly into chiral antiparallel ?-sheet structures. Our method of using the C-H stretch signals implies a general application of cSFG to study the self-assembly of bioactive, simple organic, and polymeric molecules into chiral macromolecular and supramolecular structures at interfaces, which will be useful in tackling problems, such as protein aggregation, rational design of functional materials, and fabrication of molecular devices. PMID:23458423

Wang, Zhuguang; Fu, Li; Yan, Elsa C Y

2013-03-15

75

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

76

Complex structures - smart solutions  

PubMed Central

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

2011-01-01

77

Visualizing Macromolecular Complexes with In Situ Liquid Scanning Transmission Electron Microscopy  

SciTech Connect

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

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

2012-11-01

78

Structural effect on degradability and in vivo contrast enhancement of polydisulfide Gd(III) complexes as biodegradable macromolecular MRI contrast agents  

PubMed Central

Structural effect of polydisulfide Gd(III) chelates on their in vitro degradability, and cardiovascular and tumor imaging in mice were evaluated as biodegradable macromolecular MRI contrast agents. Polydisulfide Gd(III) chelates, Gd-DTPA cystamine copolymers (GDCC), Gd-DTPA L-cystine copolymers (GDCP), Gd-DTPA D-cystine copolymers (dGDCP) and Gd-DTPA glutathione (oxidized) copolymers (GDGP), with different sizes and narrow molecular weight distribution were prepared and evaluated both in vitro and in vivo in mice bearing MDA-MB-231 tumor xenografts. Large steric hindrance around the disulfide bonds in GDGP resulted in greater T1 and T2 relaxivities than GDCC, GDCP and dGDCP. The degradability of the polydisulfide by the endogenous thiols decreased with an increase in steric effects around the disulfide bonds in the order of GDCC > GDCP, dGDCP > GDGP. The size and degradability of the contrast agents had significant impact on vascular contrast enhancement kinetics. The agents with large size and low degradability resulted in more prolonged vascular enhancement than the agents with small size and high degradability. It seems that the size and degradability of the agents did not significantly affect tumor enhancement. All agents resulted in significant contrast enhancement in tumor tissue. This study has demonstrated that the vascular enhancement kinetics of the polydisulfide MRI contrast agents can be controlled by their sizes and structures. The polydisulfide Gd(III) chelates are promising biodegradable macromolecular MRI contrast agents for MR angiography and cancer imaging.

Zong, Yuda; Wang, Xuli; Jeong, Eun-Kee; Parker, Dennis L.; Lu, Zheng-Rong

2009-01-01

79

Large-Scale Shape Changes in Proteins and Macromolecular Complexes  

NASA Astrophysics Data System (ADS)

Proteins and RNA undergo intricate motions as they carry out functions in biological systems. These motions frequently entail large-scale conformational changes that induce changes in the surface structure, or shape, of a molecule. This review describes the experimental characterization of large-scale shape changes in proteins and macromolecular complexes and the effects of such changes on macromolecular behavior. We describe several important results that have been obtained by using small-angle scattering, which is emerging as a powerful technique for determining macromolecular shapes and elucidating the quaternary structure of macromolecular assemblies.

Wall, Michael E.; Gallagher, Stephen C.; Trewhella, Jill

2000-10-01

80

Hydrodynamic Aspects of Macromolecular Solutions.  

National Technical Information Service (NTIS)

The report is an attempt in very brief form to: review some important concepts involving disperse systems (such as thermal forces, entropy, and strain energy); discuss the dynamics of molecular response to the motion of the solvent; introduce and discuss ...

M. P. Tulin

1967-01-01

81

Constructing irregular surfaces to enclose macromolecular complexes for mesoscale modeling using the discrete surface charge optimization (DISCO) algorithm  

Microsoft Academic Search

Salt-mediated electrostatics interactions play an essential role in biomolecular structures and dynamics. Because macromolecular systems modeled at atomic resolution contain thousands of solute atoms, the electrostatic computations constitute an expensive part of the force and energy calculations. Implicit solvent models are one way to simplify the model and associated calculations, but they are generally used in combination with standard atomic

Qing Zhang; Daniel A. Beard; Tamar Schlick

2003-01-01

82

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

83

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

84

The spatial organisation of macromolecular metal chelates  

NASA Astrophysics Data System (ADS)

The spatial organisation of metallopolymers (macromolecular metal chelates) is analysed on three levels; local, molecular, and supermolecular. The thermodynamic features of the formation of chelates with polymeric ligands are examined and data are presented concerning the dependence of the structure of the chelate units on various factors. The principal changes which the macrochain may undergo on formation of metal chelate centres are considered. The behaviour of the macromolecular ligands and their low-molecular- mass analogues is compared on the molecular level. The principal characteristics of the formation of intramolecular and intermolecular complexes are listed and the causes of their stability are examined. The bibliography includes 125 references.

Pomogailo, Anatolii D.; Uflyand, Igor E.; Vainshtein, E. F.

1995-09-01

85

Structure of supersaturated zincate solutions  

SciTech Connect

During the discharge of chemical power sources with zinc electrodes, supersaturated zincate solution (SZS) is formed from which zinc oxide or hydroxide precipitates as a function of time. The deposit detracts from the functioning of these power sources. In view of the model suggested for the structure of SZS, it is expected that a stabilizing effect would be exerted on SZS by compounds having proton-donating groups which do not give off the protons in the strongly alkaline medium and are not discharged in this medium. For a check of this, the authors chose to use xylitol and molasses in their experiments. The SZS were produced with a mock-up silver-zinc battery using the procedure previously described.

Dmitrenko, V.E.; Balyakina, N.N.; Baulov, V.I.; Kotov, A.V.; Zubov, M.S.

1985-09-01

86

Probing macromolecular architectures of nanosized cyclic structures of (1-->3)-beta-D-glucans by AFM and SEC-MALLS.  

PubMed

Comb-like branched (1-->3)-beta-D-glucans dissolve in water as stiff triple-helical structures. Dissociation followed by re-association leads to the formation of a blend of various macromolecular topologies, where the cyclic species make up a significant fraction. In this study, the molecular properties of these nanosized cyclic structures of (1-->3)-beta-D-glucans were probed using a combination of AFM and SEC-MALLS. The cyclic structures were obtained by subjecting linear triple-helical molecules of (1-->3)-beta-D-glucans to a denaturation-renaturation cycle, and the fraction of cyclic structures in the renatured sample was determined by AFM. Samples containing different known fractions of linear and circular molecules were studied by SEC with online multi-angle laser-light scattering and viscometric detectors. The molecular weight and the radius of gyration of the molecules eluting from the SEC column, as well as the concentration and the intrinsic viscosity, were determined simultaneously. By extrapolating the results to a situation of only circular species, the results allowed to determine the linear mass per unit length (M(L)) of not only the linear but also the circular morphologies of the (1-->3)-beta-D-glucans. The values obtained were M(L)=2140+/-180 g mol(-1)nm(-1) for the circular species and 2045+/-80 g mol(-1)nm(-1) for the linear species. This is the first direct determination of the M(L) parameter of the circular topology, and the results indicate that the reassociation of the individual chains yield a triplex structure also for the circular morphology, similar to the initial triple helix. PMID:15780261

Sletmoen, Marit; Christensen, Bjørn E; Stokke, Bjørn T

2005-04-11

87

Using NMR to Determine Protein Structure in Solution  

NASA Astrophysics Data System (ADS)

Nuclear magnetic resonance (NMR) is a marvelous spectroscopic technique that chemists, physicists, and biochemists routinely employ for their research around the world. This year half of the Nobel Prize for chemistry went to Kurt Wüthrich, who was recognized for the development of NMR-based techniques that lead to the structure determination of biomolecules in solution. In addition to implementing novel pulse sequences and software packages, Wüthrich also applied his methods to several biological systems of key importance to human health. These include the prion protein, which is heavily involved in the spongiform encephalopathy (best known as 'mad cow disease'), which recently caused numerous human deaths, particularly in the UK, due to ingestion of contaminated meat. Transverse relaxation optimized spectroscopy (TROSY) is the most intriguing new NMR method recently developed by Wüthrich and coworkers. This and other closely related pulse sequences promise to play a pivotal role in the extension of NMR to the conformational analysis of very large (up to the megadalton range) macromolecules and macromolecular complexes. More exciting new developments are expected in the near future.

Cavagnero, Silvia

2003-02-01

88

Variations in chemical composition and structure of macromolecular components in different morphological regions and maturity stages of Arundo donax  

Microsoft Academic Search

Arundo donax plants were manually separated into fractions of different morphological regions (internodes, nodes and foliage) at different stages of maturity and submitted to chemical composition studies. General chemical composition was determined by established methods. The polysaccharides were fractionated by successive extractions of holocellulose with aqueous KOH solutions. The sugar composition was determined by hydrolysis of polysaccharides followed by GC

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

1997-01-01

89

Local Kinetic Measures of Macromolecular Structure Reveal Partitioning Among Multiple Parallel Pathways from the Earliest Steps in the Folding of a Large RNA Molecule  

SciTech Connect

At the heart of the RNA folding problem is the number, structures, and relationships among the intermediates that populate the folding pathways of most large RNA molecules. Unique insight into the structural dynamics of these intermediates can be gleaned from the time-dependent changes in local probes of macromolecular conformation (e.g. reports on individual nucleotide solvent accessibility offered by hydroxyl radical ({center_dot}OH) footprinting). Local measures distributed around a macromolecule individually illuminate the ensemble of separate changes that constitute a folding reaction. Folding pathway reconstruction from a multitude of these individual measures is daunting due to the combinatorial explosion of possible kinetic models as the number of independent local measures increases. Fortunately, clustering of time progress curves sufficiently reduces the dimensionality of the data so as to make reconstruction computationally tractable. The most likely folding topology and intermediates can then be identified by exhaustively enumerating all possible kinetic models on a super-computer grid. The folding pathways and measures of the relative flux through them were determined for Mg{sup 2+} and Na{sup +}-mediated folding of the Tetrahymena thermophila group I intron using this combined experimental and computational approach. The flux during Mg{sup 2+}-mediated folding is divided among numerous parallel pathways. In contrast, the flux during the Na{sup +}-mediated reaction is predominantly restricted through three pathways, one of which is without detectable passage through intermediates. Under both conditions, the folding reaction is highly parallel with no single pathway accounting for more than 50% of the molecular flux. This suggests that RNA folding is non-sequential under a variety of different experimental conditions even at the earliest stages of folding. This study provides a template for the systematic analysis of the time-evolution of RNA structure from ensembles of local measures that will illuminate the chemical and physical characteristics of each step in the process. The applicability of this analysis approach to other macromolecules is discussed.

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

2006-01-01

90

Dynamics of Structures: Solution Techniques.  

National Technical Information Service (NTIS)

The increased use of large scale dynamic simulations in various engineering applications is apparent and time integration plays an important role. The use of direct time integration as a solution procedure for finite element semidiscretizations may be adv...

B. E. Engelmann

1988-01-01

91

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

92

'Broken symmetries' in macromolecular crystallography: phasing from unmerged data  

PubMed Central

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

Schiltz, Marc; Bricogne, Gerard

2010-01-01

93

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

PubMed Central

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

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

2010-01-01

94

Significance of wall structure, macromolecular composition, and surface polymers to the survival and transport of Cryptosporidium parvum oocysts.  

PubMed

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

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

2010-01-22

95

RapiData: a practical course in macromolecular X-ray diffraction data measurement and structure solving at the NSLS  

PubMed Central

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. M.; Soares, A.

2010-01-01

96

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

97

The design of macromolecular crystallography diffraction experiments  

PubMed Central

The measurement of X-ray diffraction data from macro­molecular crystals for the purpose of structure determination is the convergence of two processes: the preparation of diffraction-quality crystal samples on the one hand and the construction and optimization of an X-ray beamline and end station on the other. Like sample preparation, a macromolecular crystallography beamline is geared to obtaining the best possible diffraction measurements from crystals provided by the synchrotron user. This paper describes the thoughts behind an experiment that fully exploits both the sample and the beamline and how these map into everyday decisions that users can and should make when visiting a beamline with their most precious crystals.

Evans, Gwyndaf; Axford, Danny; Owen, Robin L.

2011-01-01

98

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

2012-05-29

99

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

100

Stochastic dynamics of macromolecular-assembly networks.  

NASA Astrophysics Data System (ADS)

The formation and regulation of macromolecular complexes provides the backbone of most cellular processes, including gene regulation and signal transduction. The inherent complexity of assembling macromolecular structures makes current computational methods strongly limited for understanding how the physical interactions between cellular components give rise to systemic properties of cells. Here we present a stochastic approach to study the dynamics of networks formed by macromolecular complexes in terms of the molecular interactions of their components [1]. Exploiting key thermodynamic concepts, this approach makes it possible to both estimate reaction rates and incorporate the resulting assembly dynamics into the stochastic kinetics of cellular networks. As prototype systems, we consider the lac operon and phage ? induction switches, which rely on the formation of DNA loops by proteins [2] and on the integration of these protein-DNA complexes into intracellular networks. This cross-scale approach offers an effective starting point to move forward from network diagrams, such as those of protein-protein and DNA-protein interaction networks, to the actual dynamics of cellular processes. [1] L. Saiz and J.M.G. Vilar, submitted (2005). [2] J.M.G. Vilar and L. Saiz, Current Opinion in Genetics & Development, 15, 136-144 (2005).

Saiz, Leonor; Vilar, Jose

2006-03-01

101

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

Microsoft Academic Search

The distributions of sulphur-containing compounds generated by flash pyrolysis of macromolecular sedimentary\\u000aorganic matter (kerogen, coal, asphaltenes) were studied by gas chromatography in combination with S-selective\\u000aflame photometric detection or mass spectrometry. The abundance of S-containing pyrolysis products in the\\u000apyrolysates relative to other products was highly variable depending on the sample but the types of products were\\u000agenerally similar,

J. S. Sinninghe Damsté; T. I. Eglinton; J. W. de Leeuw; P. A. Schenk

1989-01-01

102

Energy transfer in macromolecular arrays  

NASA Astrophysics Data System (ADS)

Macromolecular systems comprised of many light-sensitive centres (the photosynthetic unit, dendrimers, and other highly symmetric multichromophore arrays) are important structures offering challenges to theoreticians and synthetic chemists alike. Here we outline novel photophysical interactions predicted and observed in such arrays. Using the tools of molecular quantum electrodynamics (QED) we present quantum amplitudes for a variety of higher-order resonance energy transfer (RET) schemes associated with well-known nonlinear optical effects such as two- and three-photon absorption. The initial analysis is extended to account for situations where the participant donor species are identical and exist in a highly symmetric environment, leading to the possible formation of excitons. It emerges from the QED theory that such excitons are closely associated with the higher-order RET processes. General results are interpreted by analyzing particular molecular architectures which offer interesting features such as rate enhancement or limitation and exciton pathway quenching. Applications in the areas of photosynthesis, molecular logic gates and low-intensity fluorescence energy transfer are predicted.

Andrews, David L.; Jenkins, Robert D.

2003-11-01

103

Building Macromolecular Assemblies by Information-driven Docking  

PubMed Central

Over the last years, large scale proteomics studies have generated a wealth of information of biomolecular complexes. Adding the structural dimension to the resulting interactomes represents a major challenge that classical structural experimental methods alone will have difficulties to confront. To meet this challenge, complementary modeling techniques such as docking are thus needed. Among the current docking methods, HADDOCK (High Ambiguity-Driven DOCKing) distinguishes itself from others by the use of experimental and/or bioinformatics data to drive the modeling process and has shown a strong performance in the critical assessment of prediction of interactions (CAPRI), a blind experiment for the prediction of interactions. Although most docking programs are limited to binary complexes, HADDOCK can deal with multiple molecules (up to six), a capability that will be required to build large macromolecular assemblies. We present here a novel web interface of HADDOCK that allows the user to dock up to six biomolecules simultaneously. This interface allows the inclusion of a large variety of both experimental and/or bioinformatics data and supports several types of cyclic and dihedral symmetries in the docking of multibody assemblies. The server was tested on a benchmark of six cases, containing five symmetric homo-oligomeric protein complexes and one symmetric protein-DNA complex. Our results reveal that, in the presence of either bioinformatics and/or experimental data, HADDOCK shows an excellent performance: in all cases, HADDOCK was able to generate good to high quality solutions and ranked them at the top, demonstrating its ability to model symmetric multicomponent assemblies. Docking methods can thus play an important role in adding the structural dimension to interactomes. However, although the current docking methodologies were successful for a vast range of cases, considering the variety and complexity of macromolecular assemblies, inclusion of some kind of experimental information (e.g. from mass spectrometry, nuclear magnetic resonance, cryoelectron microscopy, etc.) will remain highly desirable to obtain reliable results.

Karaca, Ezgi; Melquiond, Adrien S. J.; de Vries, Sjoerd J.; Kastritis, Panagiotis L.; Bonvin, Alexandre M. J. J.

2010-01-01

104

Developments in macromolecular drug delivery.  

PubMed

Macromolecular drugs hold great promise as novel therapeutics of several major disorders, such as cancer and cardiovascular disease. However, their use is limited by lack of efficient, safe, and specific delivery strategies. Successful development of such strategies requires interdisciplinary collaborations involving researchers with expertise on, e.g., polymer chemistry, cell biology, nanotechnology, systems biology, advanced imaging methods, and clinical medicine. This not only poses obvious challenges to the scientific community but also provides opportunities for the unexpected at the interface between different disciplines. This introductory chapter summarizes and gives references to studies on macromolecular delivery that should be of interest to a broad scientific audience involved in macromolecular drug synthesis as well as in vitro and in vivo drug delivery studies. PMID:19085127

Belting, Mattias; Wittrup, Anders

2009-01-01

105

Fractal organisation in biological macromolecular lattices.  

PubMed

Macromolecular solutions of proteic, glycoproteic or polysaccharidic nature in the presence of salt gave rise (when slowly dried) to dendritic-like fractal patterns. A fractal dimension D = 1.79 +/- 0.018 was obtained for dendritic patterns of a sonicated ovomucin gel (40% ovomucin-60% ovalbumin) in the presence of 0.1 M NaCl. The calculated D is similar to that described in percolation clusters. The appearance of fractal patterns was dependent upon the protein:salt ratio with an optimum in the range 0.75-1.25. Patterns disappeared at either lower or higher ratios. We conclude that the salt percolates through the macromolecular lattice and precipitates in fractal clusters during the drying process. Dendritic-like fractal patterns with similar D and morphologies were obtained with solutions of fetuin, ovalbumin, albumin or starch suggesting that fractal patterning is a general property of biological polymers. That cellular polymers would also aggregate in a fractal way was implied from the analysis of cellular cytoskeleton and microtrabecular lattices. PMID:1524703

Rabouille, C; Cortassa, S; Aon, M A

1992-04-01

106

Folding dynamics of Trp-cage in the presence of chemical interference and macromolecular crowding. I  

NASA Astrophysics Data System (ADS)

Proteins fold and function in the crowded environment of the cell's interior. In the recent years it has been well established that the so-called ``macromolecular crowding'' effect enhances the folding stability of proteins by destabilizing their unfolded states for selected proteins. On the other hand, chemical and thermal denaturation is often used in experiments as a tool to destabilize a protein by populating the unfolded states when probing its folding landscape and thermodynamic properties. However, little is known about the complicated effects of these synergistic perturbations acting on the kinetic properties of proteins, particularly when large structural fluctuations, such as protein folding, have been involved. In this study, we have first investigated the folding mechanism of Trp-cage dependent on urea concentration by coarse-grained molecular simulations where the impact of urea is implemented into an energy function of the side chain and/or backbone interactions derived from the all-atomistic molecular dynamics simulations with urea through a Boltzmann inversion method. In urea solution, the folding rates of a model miniprotein Trp-cage decrease and the folded state slightly swells due to a lack of contact formation between side chains at the terminal regions. In addition, the equilibrium m-values of Trp-cage from the computer simulations are in agreement with experimental measurements. We have further investigated the combined effects of urea denaturation and macromolecular crowding on Trp-cage's folding mechanism where crowding agents are modeled as hard-spheres. The enhancement of folding rates of Trp-cage is most pronounced by macromolecular crowding effect when the extended conformations of Trp-cast dominate at high urea concentration. Our study makes quantitatively testable predictions on protein folding dynamics in a complex environment involving both chemical denaturation and macromolecular crowding effects.

Samiotakis, Antonios; Cheung, Margaret S.

2011-11-01

107

Structure and Dynamics of Calmodulin in Solution  

Microsoft Academic Search

To characterize the dynamic behavior of calmodulin in solution, we have carried out molecular dynamics (MD) simulations of the Ca2+-loaded structure. The crystal structure of calmodulin was placed in a solvent sphere of radius 44Å, and 6 Cl? and 22 Na+ ions were included to neutralize the system and to model a 150mM salt concentration. The total number of atoms

Willy Wriggers; Ernest Mehler; Felicia Pitici; Harel Weinstein; Klaus Schulten

1998-01-01

108

Transmucosal macromolecular drug delivery.  

PubMed

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 carriers represents a challenging but promising strategy. The present paper aims to compare the characteristics and potential of nanostructures based on the mucoadhesive polysaccharide chitosan (CS). These are CS nanoparticles, CS-coated oil nanodroplets (nanocapsules) and CS-coated lipid nanoparticles. The characteristics and behavior of CS nanoparticles and CS-coated lipid nanoparticles already reported [A. Vila, A. Sanchez, M. Tobio, P. Calvo, M.J. Alonso, Design of biodegradable particles for protein delivery, J. Control. Rel. 78 (2002) 15-24; R. Fernandez-Urrusuno, P. Calvo, C. Remunan-Lopez, J.L. Vila-Jato, M.J. Alonso, Enhancement of nasal absorption of insulin using chitosan nanoparticles, Pharm. Res. 16 (1999) 1576-1581; M. Garcia-Fuentes, D. Torres, M.J. Alonso, New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin (submitted for publication).] are compared with those of CS nanocapsules originally reported here. The three types of systems have a size in the nanometer range and a positive zeta potential that was attributed to the presence of CS on their surface. They showed an important capacity for the association of peptides such as insulin, salmon calcitonin and proteins, such as tetanus toxoid. Their mechanism of interaction with epithelia was investigated using the Caco-2 model cell line. The results showed that CS-coated systems caused a concentration-dependent reduction in the transepithelial resistance of the cell monolayer. Moreover, within the range of concentrations investigated, these systems were internalized in the monolayer in a concentration-dependent manner. This uptake was slightly enhanced by the presence of the CS coating but, as compared with previously published results [M. Garcia-Fuentes, C. Prego, D. Torres, M.J. Alonso, Triglyceride-chitosan nanostructures for oral calcitonin delivery: evaluation in the Caco-2 cell model and in vivo (submitted for publication)], highly dependent on the nature of the lipid core. Nevertheless, these differences in the uptake of the CS-coated systems (solid lipid core or oily core) by the Caco-2 cells did not have a consequence in the in vivo behaviour. Indeed, both CS-coated systems (nanocapsules and CS-coated nanoparticles) showed an important capacity to enhance the intestinal absorption of the model peptide, salmon calcitonin, as shown by the important and long-lasting decrease in the calcemia levels observed in rats. PMID:15588901

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

2005-01-01

109

Molecular Control of Macromolecular Properties  

NASA Astrophysics Data System (ADS)

Molecular level control over macromolecules has been at the heart of human advancement, long before Hermann Staudinger coined the term Makromolekule. From the development of primitive pharmaceuticals to the advanced materials that sent Man into outer-space, We have been tinkering with God's paint since our inception. The work described herein primarily involves advances concerning poly-aromatic macromolecules for use in future electronic applications, particularly that of organic photovoltaics. There is a final chapter, however, that gives the reader a taste of how some molecular level changes can be directly visualized with modern microscopy techniques. Chapter 1 provides a very brief introduction to conjugated polymers and molecular level control over macromolecular properties. Chapters 2--4 introduces the concept of polymer substitution as a means by which to control and improve charge generation in organic photovoltaic devices. Chapters 5 and 6 show how these polymers can take on larger, defined structures, yet are still beholden to intrinsic molecular properties---such as regioregularity, a fancy word for the regularity of the position in which two aromatic rings are joined together. Chapter 7 re-examines the role of polymer substitution on photovoltaic performance, this time with an emphasis on homo-polymer packing rather than electron transfer at the donor/acceptor interface. Finally, Chapter 8 visualizes how controlling the environment about a single metal atom can lead directly to a cyclic polyolefin. Individually, these advances do not yield any breakthroughs noticeable to a general audience; collectively, they sit atop a mountain of human knowledge, waiting to provide a stepping stone for the next generation.

Holcombe, Thomas Wesley, III

110

Supersaturated zincate solutions: A structural study  

SciTech Connect

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

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

1995-05-01

111

Solvent isotope effect on macromolecular dynamics in E. coli.  

PubMed

Elastic incoherent neutron scattering was used to explore solvent isotope effects on average macromolecular dynamics in vivo. Measurements were performed on living E. coli bacteria containing H2O and D2O, respectively, close to physiological conditions of temperature. Global macromolecular flexibility, expressed as mean square fluctuation (MSF) values, and structural resilience in a free energy potential, expressed as a mean effective force constant, [Symbol: see text]k'[Symbol: see text], were extracted in the two solvent conditions. They referred to the average contribution of all macromolecules inside the cell, mostly dominated by the internal motions of the protein fraction. Flexibility and resilience were both found to be smaller in D2O than in H2O. A difference was expected because the driving forces behind macromolecular stabilization and dynamics are different in H2O and D2O. In D2O, the hydrophobic effect is known to be stronger than in H2O: it favours the burial of non-polar surfaces as well as their van der Waals' packing in the macromolecule cores. This may lead to the observed smaller MSF values. In contrast, in H2O, macromolecules would present more water-exposed surfaces, which would give rise to larger MSF values, in particular at the macromolecular surface. The smaller [Symbol: see text]k'[Symbol: see text] value suggested a larger entropy content in the D2O case due to increased sampling of macromolecular conformational substates. PMID:18286276

Jasnin, Marion; Tehei, Moeava; Moulin, Martine; Haertlein, Michael; Zaccai, Giuseppe

2008-02-20

112

Quaternary structure of hemoglobin in solution  

NASA Astrophysics Data System (ADS)

Many important proteins perform their physiological functions under allosteric control, whereby the binding of a ligand at a specific site influences the binding affinity at a different site. Allosteric regulation usually involves a switch in protein conformation upon ligand binding. The energies of the corresponding structures are comparable, and, therefore, the possibility that a structure determined by x-ray diffraction in the crystalline state is influenced by its intermolecular contacts, and thus differs from the solution structure, cannot be excluded. Here, we demonstrate that the quaternary structure of tetrameric human normal adult carbonmonoxy-hemoglobin can readily be determined in solution at near-physiological conditions of pH, ionic strength, and temperature by NMR measurement of 15N-1H residual dipolar couplings in weakly oriented samples. The structure is found to be a dynamic intermediate between two previously solved crystal structures, known as the R and R2 states. Exchange broadening at the subunit interface points to a rapid equilibrium between different structures that presumably include the crystallographically observed states.

Lukin, Jonathan A.; Kontaxis, Georg; Simplaceanu, Virgil; Yuan, Yue; Bax, Ad; Ho, Chien

2003-01-01

113

Probing the Macromolecular Organization of Cells by Electron Tomography  

PubMed Central

Summary A major goal in cell biology is to understand the functional organization of macromolecular complexes in vivo. Electron microscopy is helping cell biologists to achieve this goal, thanks to its ability to resolve structural details in the nanometer range. While issues related to specimen preparation, imaging, and image interpretation make this approach to cell architecture difficult, recent improvements in methods, equipment, and software have facilitated the study of both important macromolecular complexes and comparatively large volumes from cellular specimens. Here, we describe recent progress in electron microscopy of cells and the ways in which the relevant methodologies are helping to elucidate cell architecture.

Hoenger, Andreas; McIntosh, J. Richard

2010-01-01

114

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

115

Polysiloxanes in macromolecular architecture  

Microsoft Academic Search

In this review some recent advances regarding siloxane materials with non-linear architectures are discussed. Cyclic, branched and network structures are reviewed, the three main areas covered being (1) macrocyclic siloxanes, (2) hyperbranched polymers and (3) interpenetrating siloxane networks. Recent concepts and synthetic strategies for manipulating siloxane architectures are explored. Also reviewed are the specific and unusual material science properties of

R Bischoff; S. E Cray

1999-01-01

116

Solution structure and dynamics of mouse ARMET.  

PubMed

ARMET is an endoplasmic reticulum (ER) stress-inducible protein that is required for maintaining cell viability under ER stress conditions. However, the exact molecular mechanisms by which ARMET protects cells are unknown. Here, we have analyzed the solution structure of ARMET. ARMET has an entirely alpha-helical structure, which is composed of two distinct domains. Positive charges are dispersed on the surfaces of both domains and across a linker structure. Trypsin digestion and (15)N relaxation experiments indicate that the tumbling of the N-terminal and C-terminal domains is effectively independent. These results suggest that ARMET may hold a negatively charged molecule using the two positively charged domains. PMID:20214902

Hoseki, Jun; Sasakawa, Hiroaki; Yamaguchi, Yoshiki; Maeda, Momoe; Kubota, Hiroshi; Kato, Koichi; Nagata, Kazuhiro

2010-03-06

117

Generating triangulated macromolecular surfaces by Euclidean Distance Transform.  

PubMed

Macromolecular surfaces are fundamental representations of their three-dimensional geometric shape. Accurate calculation of protein surfaces is of critical importance in the protein structural and functional studies including ligand-protein docking and virtual screening. In contrast to analytical or parametric representation of macromolecular surfaces, triangulated mesh surfaces have been proved to be easy to describe, visualize and manipulate by computer programs. Here, we develop a new algorithm of EDTSurf for generating three major macromolecular surfaces of van der Waals surface, solvent-accessible surface and molecular surface, using the technique of fast Euclidean Distance Transform (EDT). The triangulated surfaces are constructed directly from volumetric solids by a Vertex-Connected Marching Cube algorithm that forms triangles from grid points. Compared to the analytical result, the relative error of the surface calculations by EDTSurf is <2-4% depending on the grid resolution, which is 1.5-4 times lower than the methods in the literature; and yet, the algorithm is faster and costs less computer memory than the comparative methods. The improvements in both accuracy and speed of the macromolecular surface determination should make EDTSurf a useful tool for the detailed study of protein docking and structure predictions. Both source code and the executable program of EDTSurf are freely available at http://zhang.bioinformatics.ku.edu/EDTSurf. PMID:19956577

Xu, Dong; Zhang, Yang

2009-12-02

118

'Hot' Macromolecular Crystals  

SciTech Connect

Transcriptional regulator protein TM1030 from the hyperthermophile Thermotoga maritima, as well as its complex with DNA, was crystallized at a wide range of temperatures. Crystallization plates were incubated at 4, 20, 37, and 50 C over 3 weeks. The best crystals of TM1030 in complex with DNA were obtained at 4, 20, and 37 C, while TM1030 alone crystallized almost equally well in all temperatures. The crystals grown at different temperatures were used for X-ray diffraction experiments and their structures were compared. Surprisingly, the models of TM1030 obtained from crystals grown at different temperatures are similar in quality. While there are some examples of structures of proteins grown at elevated temperatures in the PDB, these temperatures appear to be underrepresented. Our studies show that crystals of some proteins may be grown and are stable at broad range of temperatures. We suggest that crystallization experiments at elevated temperatures could be used as a standard part of the crystallization protocol.

Koclega, Katarzyna D.; Chruszcz, Maksymilian; Zimmerman, Matthew D.; Bujacz, Grzegorz; Minor, Wladek (UV); (ITB-Poland)

2010-09-07

119

MACROMOLECULAR PHYSIOLOGY OF PLASTIDS  

PubMed Central

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

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

1970-01-01

120

Searching for likeness in a database of macromolecular complexes.  

PubMed

A software tool and workflow based on distance geometry is presented that can be used to search for local similarity in substructures in a comprehensive database of experimentally derived macromolecular structure. The method does not rely on fold annotation, specific secondary structure assignments, or sequence homology and may be used to locate compound substructures of multiple segments spanning different macromolecules that share a queried backbone geometry. This generalized substructure searching capability is intended to allow users to play an active part in exploring the role specific substructures play in larger protein domains, quaternary assemblies of proteins, and macromolecular complexes of proteins and polynucleotides. The user may select any portion or portions of an existing structure or complex to serve as a template for searching, and other structures that share the same structural features are identified, retrieved and overlaid to emphasize substructural likeness. Matching structures may be compared using a variety of integrated tools including molecular graphics for structure visualization and matching substructure sequence logos. A number of examples are provided that illustrate how generalized substructure searching may be used to understand both the similarity, and individuality of specific macromolecular structures. Web-based access to our substructure searching services is freely available at https://drugsite.msi.umn.edu . PMID:24047445

Van Voorst, Jeffrey R; Finzel, Barry C

2013-10-09

121

Structure and Properties of Solid Solutions.  

National Technical Information Service (NTIS)

Contents: solid solution strengthening and strain aging in Ag-base Al alloys; solid solution strengthening and aging in Cu-base Al alloys; solid solution strengthening in NaCl-base NaBr solutions; short-range order; solid solution strength in the gold-sil...

M. E. Fine

1964-01-01

122

The effect of macromolecular crowding, ionic strength and calcium binding on calmodulin dynamics  

NASA Astrophysics Data System (ADS)

The flexibility in the structure of calmodulin (CaM) allows its binding to over 300 target proteins in the cell. To investigate the structure-function relationship of CaM in response to the changing intracellular environment, we use a combined method of computer simulation and experiments based on circular dichroism (CD). The conformation, helicity and EF hand orientation of CaM are analyzed computationally to address the effect of macromolecular crowding, ionic strength and calcium binding in the experiments. We applied a unique solution of charges computed from QM/MM to accurately represent the charge distribution in the transition from apo-CaM to holo-CaM. Computationally, we found that a high level of macromolecular crowding, in addition to calcium binding and ionic strength, can impact the conformation, helicity and the EF hand orientation of CaM. Our result may provide unique insight into understanding the promiscuous behavior of calmodulin in target selection inside cells.

Wang, Qian; Liang, Kao-Chen; Waxham, Neal; Cheung, Margaret

2011-03-01

123

Organoactinide chemistry: synthesis, structure, and solution dynamics  

SciTech Connect

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

Brennan, J.G.

1985-12-01

124

Structure of flexible telechelic zwitterions in solutions  

NASA Astrophysics Data System (ADS)

We have performed preliminary small angle neutron scattering (SANS) experiments on a series of solutions of zwitterionic telechelic polysterene (ZT-PS) of low molecular weight, with the general formula: Br-Me3N+-C6H4-[CH2CH(C6H5)]n-C(C6H5)2-(CH2)3-SO3-Li+. In addition, preliminary SANS experiments were carried out. Polymers were dissolved in non-polar (toluene) and polar (cyclohexanone) solvents. Concentrations studied ranged from 0.5%gmol-1 to 16.8%gmol-1. We observed small differences in the structural factors above q=0.5Å-1 depending on the type of solvent. Below q=0.5Å-1 there is a significant upturn in the scattering, which changes with the concentration of the polymer and the type of solvent. Complementary SANS measurements showed a clustering effect for zwitterions in a non-polar solvent.

Zaja?c, W.; Gabry?, B. J.; Bucknall, D. G.; Xu, J.; Richards, R. W.; Hutchings, L.

2004-07-01

125

Combined effects of agitation, macromolecular crowding, and interfaces on amyloidogenesis.  

PubMed

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

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

2012-09-17

126

Temperature-dependent macromolecular X-ray crystallography.  

PubMed

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

Weik, Martin; Colletier, Jacques Philippe

2010-03-24

127

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

128

International summer school on macromolecular crystallographic computing. Final report  

SciTech Connect

The School was the seventh in a series of International Union of Crystallography (IUCr) Crystallographic Symposia. The format of the School was formal lectures in the morning, tutorials in the afternoon, and software demonstrations and more lectures in the evening. The full program which left both the organizers and attendees exhausted, reflects the current state of excitement in the field of macromolecular structure determination using the technique of X-ray crystallography. The new and improved technologies and techniques described in these Proceedings are contributing to that growth and at the same time, as pointed out in the paper given by Sussman, creating challenges for the Protein Data Bank (PDB). As the School progressed, the authors were struck by the similarities to events which took place in small molecule crystallography beginning some 20 to 25 years ago. Growth then was fueled by the advent of new algorithms, affordable computer hardware, and good software. So it is today for macromolecular crystallography, but with the added bonus of the Internet which is changing how scientist conduct their research. Flack presented this view as part of his on-going contribution to how crystallographers use the Internet. After presentations discussing structures en masse they returned to the more traditional mode of presentation which parallels the determination of a single macromolecular structure: data collection -- phasing -- model building and visualization -- refinement.

NONE

1998-08-01

129

Supersaturated zincate solutions: A structural study  

Microsoft Academic Search

The anodic oxidation of zinc electrodes in concentrated potassium hydroxide solutions that occurs during the discharge of alkaline zinc batteries leads to electrolytes with a Zn(II) content much higher than that obtained when a solid ZnO is equilibrated with KOH solutions of the same concentration at the same temperature. The Zn(II) excess slowly precipitates as ZnO from these supersaturated solutions,

C. Debiemme-Chouvy; J. Vedel; M. Bellissent-Funel; R. Cortes

1995-01-01

130

A macromolecular model for the endothelial surface layer  

NASA Astrophysics Data System (ADS)

The endothelial surface layer (ESL) is a micron-scale macromolecular lining of the luminal side of blood vessels composed of proteoglycans, glycoproteins, polysaccharides and associated plasma proteins all in dynamic equilibrium. It has numerous physiological roles including the regulation of blood flow and microvascular permeability, and active participation in mechanotransduction and stress regulation, coagulation, cell adhesion, and inflammatory response. The dynamic structure and the mechanical properties of the ESL are crucial for many of its physiological properties. We present a topological model for the ESL composed of three basic macromolecular elements: branched proteoglycans, linear polysaccharide chains, and small plasma proteins. The model was studied using non-equilibrium molecular dynamics simulations and compared with scaling theories for associating tethered polymers. We discuss the observed dynamical and mechanical properties of the ESL captured by this model, and the possible physical insight it provides into the physiological behavior of the ESL.

Harden, James; Danova-Okpetu, Darina; Grest, Gary

2006-03-01

131

Dielectric and structural properties of aqueous nonpolar solute mixtures.  

PubMed

The dielectric properties and molecular structure of water mixtures with different nonpolar solutes (methane and noble gases) are studied using molecular dynamics. The water-water, water-solute, and solute-solute interactions are calculated using the combination of a polarizable potential [J. Li, Z. Zhou, and R. J. Sadus, J. Chem. Phys. 127, 154509 (2007)] for water plus the Lennard-Jones potential. The effect of solute size and concentration on the solubility of the system, hydrogen bonding, dielectric constant, and dipole moment are investigated over a temperature range of 278-750 K and solute percentage mole fractions up to 30%. Solute particles affect the structure of water, resulting in the compression of oxygen-oxygen and oxygen-hydrogen radial distribution functions. The influence of the solute extends both to relatively low concentrations and high temperatures. The coordination numbers of aqueous solutions of the nonpolar solutes appear to be proportional to the size of the solute particles. Our study shows the destructive influence of the nonpolar solute on both the tetrahedral water structure and hydrogen bond formation at solute concentrations greater than 30%. The presence of nonpolar particles typically decreases both the dielectric constant and dipole moment. The decrease of dielectric constant and water dipole moment is directly proportional to the solute concentration and temperature. PMID:23020337

Shvab, I; Sadus, Richard J

2012-09-28

132

Heuristic Refinement Method for Deriving Solution Structures of Proteins.  

National Technical Information Service (NTIS)

A new method is presented for determining structures of proteins in solution. The method uses constraints inferred from analytic data to successively refine both the locations for parts of the structure and the levels of detail for describing those parts....

B. G. Buchanan B. Hayes-Roth O. Lichtarge R. Altman J. Brinkley M. Hewett C. Cornelius B. Duncan O. Jardetzky

1986-01-01

133

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

134

Viscosity of aqueous solutions and local microscopic structure.  

PubMed

The effect of solutes on the structure of water has been debated intensively over the past years. Typical scenarios label different ions as water structure "makers" or "breakers": this is a quite elusive definition, which has been first introduced in the description of the effect of solutes on the viscosity of water and, although criticized, is still used in the current literature. Here, using a combination of neutron diffraction and computer modeling, we present a possible relation between the viscosity B coefficient and a local structural property of the solution. In particular, B appears in the Jones-Dole relation and its sign is traditionally used to characterize a solute as "structure maker" or "breaker". We find that B is linearly correlated to the difference between the average solute-water distance and the water-water distance in the pure liquid, in the case of monovalent electrolyte solutions. PMID:21859162

Corridoni, T; Mancinelli, R; Ricci, M A; Bruni, F

2011-08-23

135

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

136

On the particulate structure of cellulose solutions  

Microsoft Academic Search

A simple model for aggregate formation in cellulose solutions is presented. Owing to a strong tendency of hydrogen-bond formation among the cellulose molecules, aggregation does not lead to a completely random arrangement of the molecules. In a core, parts of the chain molecules are laterally aligned. This core is surrounded by disordered regions that give rise to the formation of

Bernd Morgenstern; Hans-Werner Kammer

1999-01-01

137

Joint use of small-angle X-ray and neutron scattering to study biological macromolecules in solution  

Microsoft Academic Search

Novel techniques for simultaneous analysis of X-ray and neutron scattering patterns from macromolecular complexes in solution are presented. They include ab initio shape and internal structure determination of multicomponent particles and more detailed rigid body modeling of complexes using high resolution structures of subunits. The methods fit simultaneously X-ray and neutron scattering curves including contrast variation data sets from selectively

Maxim V. Petoukhov; Dmitri I. Svergun

2006-01-01

138

Multi-crystal Anomalous Diffraction for Low-resolution Macromolecular Phasing  

SciTech Connect

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

Q Liu; Z Zhang; W Hendrickson

2011-12-31

139

The macromolecular structure of human cervical-mucus glycoproteins. Studies on fragments obtained after reduction of disulphide bridges and after subsequent trypsin digestion.  

PubMed Central

Human cervical-mucus glycoproteins (mucins) were extracted with 6 M-guanidinium chloride in the presence of proteinase inhibitors and purified by isopycnic density-gradient centrifugation. The whole mucins (Mr approx. 10 X 10(6] were degraded into 'subunits' (Mr approx. 2 X 10(6] by reduction of disulphide bonds. Trypsin digestion of the 'subunits' produced glycopeptides with Mr approx. 380000, which appear to be rod-like with a length of approx. 105 nm. The relationship between the radius of gyration and the Mr value obtained by light-scattering for whole mucins, 'subunits' and 'domains' suggest that cervical-mucus glycoproteins are linear flexible macromolecules composed of, on the average, four or five 'domains'/subunit and four subunits/whole mucin macromolecule. The shape-dependent particle scattering function for the whole mucins and the 'subunits' are in accordance with that of a linear flexible chain. No evidence for a branched or a star-like structure was found. A tentative model for cervical mucins is proposed.

Carlstedt, I; Lindgren, H; Sheehan, J K

1983-01-01

140

Complexation of Actinides in Solution: Thermodynamic Measurementsand Structural Characterization  

SciTech Connect

This paper presents a brief introduction of the studies of actinide complexation in solution at Lawrence Berkeley National Laboratory. An integrated approach of thermodynamic measurements and structural characterization is taken to obtain fundamental understanding of actinide complexation in solution that is of importance in predicting the behavior of actinides in separation processes and environmental transport.

Rao, L.

2007-02-01

141

The Solution Structure of (+)-Spongistatin 1 in DMSO  

PubMed Central

The solution structure of (+)-spongistatin 1 (1) has been determined, via 1- and 2-D NMR techniques in conjunction with extensive in silico conformational analysis, to comprise a mixture of 4 major rapidly interconverting conformational families.

Atasoylu, Onur; Furst, George; Risatti, Christina; Smith, Amos B.

2010-01-01

142

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

143

Probing the structure of RNAs in solution.  

PubMed Central

During these last years, a powerful methodology has been developed to study the secondary and tertiary structure of RNA molecules either free or engaged in complex with proteins. This method allows to test the reactivity of every nucleotide towards chemical or enzymatic probes. The detection of the modified nucleotides and RNase cleavages can be conducted by two different paths which are oriented both by the length of the studied RNA and by the nature of the probes used. The first one uses end-labeled RNA molecule and allows to detect only scissions in the RNA chain. The second approach is based on primer extension by reverse transcriptase and detects stops of transcription at modified or cleaved nucleotides. The synthesized cDNA fragments are then sized by electrophoresis on polyacrylamide:urea gels. In this paper, the various structure probes used so far are described, and their utilization is discussed. Images

Ehresmann, C; Baudin, F; Mougel, M; Romby, P; Ebel, J P; Ehresmann, B

1987-01-01

144

Solution Structure and Backbone Dynamics of Streptopain  

PubMed Central

Streptococcal pyrogenic exotoxin B (SPE B) is a cysteine protease expressed by Streptococcus pyogenes. The D9N, G163S, G163S/A172S, and G239D mutant proteins were expressed to study the effect of the allelic variants on their protease activity. In contrast to other mutants, the G239D mutant was ?12-fold less active. The Gly-239 residue is located within the C-terminal S230-G239 region, which cannot be observed in the x-ray structure. The three-dimensional structure and backbone dynamics of the 28-kDa mature SPE B (mSPE B) were determined. Unlike the x-ray structure of the 40-kDa zymogen SPE B (proSPE B), we observed the interactions between the C-terminal loop and the active site residues in mSPE B. The structural differences between mSPE B and proSPE B were the conformation of the C-terminal loop and the orientation of the catalytic His-195 residue, suggesting that activation and inactivation of SPE B is involved in the His-195 side-chain rotation. Dynamics analysis of mSPE B and the mSPE B/inhibitor complexes showed that the catalytic and C-terminal loops were the most flexible regions with low order parameter values of 0.5 to 0.8 and exhibited the motion on the ps/ns timescale. These findings suggest that the flexible C-terminal loop of SPE B may play an important role in controlling the substrate binding, resulting in its broad substrate specificity.

Wang, Chih-Chieh; Houng, Hsiang-Chee; Chen, Chun-Liang; Wang, Pei-Ju; Kuo, Chih-Feng; Lin, Yee-Shin; Wu, Jiunn-Jong; Lin, Ming T.; Liu, Ching-Chuan; Huang, Wenya; Chuang, Woei-Jer

2009-01-01

145

FitEM2EM---Tools for Low Resolution Study of Macromolecular Assembly and Dynamics  

Microsoft Academic Search

Studies of the structure and dynamics of macromolecular assemblies often involve comparison of low resolution models obtained using different techniques such as electron microscopy or atomic force microscopy. We present new computational tools for comparing (matching) and docking of low resolution structures, based on shape complementarity. The matched or docked objects are represented by three dimensional grids where the value

Ziv Frankenstein; Joseph Sperling; Ruth Sperling; Miriam Eisenstein; Che John Connon

2008-01-01

146

Macromolecular and chemical changes induced by air-oxidation of a medium volatile bituminous coal  

Microsoft Academic Search

The heterogeneity of coal, together with its complex macromolecular nature, has been responsible for much of the difficulties in elucidating its structure and chemical characterization. Most methods of investigation of the chemical structure and physical properties involve breaking macromolecules into smaller fragments by depolymerization, oxidation, reduction, dehydrogenation, acetylation, etc., which, for the most part, solubilizes a major fraction of the

D. Schwartz; P. J. Hall; H. Marsh

1988-01-01

147

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

148

Macromolecular mobility inside the cell nucleus  

Microsoft Academic Search

The highly organized interior of the living cell imposes major constraints on the dynamic properties of macromolecules and macromolecular complexes in both the cytoplasm and the nucleus. Although there are many examples of cytoplasmic molecular assemblies that can be propelled by molecular motors along microtubules and actin filaments, a view that had emerged during the past few years was that

Maria Carmo-Fonseca; Melpomeni Platani; Jason R. Swedlow

2002-01-01

149

Bayesian Weighting for Macromolecular Crystallographic Refinement  

Microsoft Academic Search

A simple weighting scheme for atomic refinement is discussed. The approach, called 'Bayesian weighting', is designed to be robust with respect to the bias that arises from the incomplete nature of the atomic model, which in macromolecular crystallography is typically quite serious. Bayesian weights are based on the mean- squared residual errors over shells of resolution, with centric and acentric

THOMAS C. TERWILLIGER; JOEL BERENDZEN

1996-01-01

150

Solution Structures of Rat Amylin Peptide: Simulation, Theory, and Experiment  

Microsoft Academic Search

Amyloid deposits of amylin in the pancreas are an important characteristic feature found in patients with Type-2 diabetes. The aggregate has been considered important in the disease pathology and has been studied extensively. However, the secondary structures of the individual peptide have not been clearly identified. In this work, we present detailed solution structures of rat amylin using a combination

Allam S. Reddy; Lu Wang; Yu-Shan Lin; Yun Ling; Manan Chopra; Martin T. Zanni; James L. Skinner; Juan J. De Pablo

2010-01-01

151

Crystal structure solution from experimentally determined atomic pair distribution functions  

Microsoft Academic Search

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

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

2010-01-01

152

Influence of container structures and content solutions on dispensing time of ophthalmic solutions  

PubMed Central

Purpose To investigate the influence of container structures and content solutions on the time of dispensing from eye dropper bottles. Methods Eye dropper bottle models, solution models (filtrate water/surfactant solution) and a dispensing time measuring apparatus were prepared to measure the dispensing time. Results With filtrate water and pressure thrust load of 0.3 MPa, the dispensing time significantly increased from 1.1 ± 0.5 seconds to 4.6 ± 1.1 seconds depending on the decrease of inner aperture diameters from 0.4 mm to 0.2 mm (P < 0.0001). When using the bottle models with inner aperture diameters of 0.4 mm or larger, the dispensing time became constant. The dispensing time using surfactant solution showed the same tendency as above. When pressure thrust load was large (0.07 MPa), the solution flew out continuously with inner aperture diameters of 0.4 mm or larger and the dispensing time could not be measured. The inner aperture diameter most strongly explained the variation of the dispensing time in both the content solutions in the multiple linear regression analysis (filtrate water: 46%, R2 = 0.462, surfactant solution: 56%, R2 = 0.563). Conclusions Among content solutions and container structures, the dispensing time was mostly influenced by the diameter of the inner aperture of bottles.

Yoshikawa, Keiji; Yamada, Hiroshi

2010-01-01

153

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

154

Surface structure solution by x-ray diffraction: structure solution by non-negativity and atomicity constraints  

NASA Astrophysics Data System (ADS)

We propose a method for the solution of surface structures from x-ray diffraction based on the phasing of measured structure factor amplitudes in two stages: first the incorporation of calculated amplitudes and phases of the structure factors of the known underlying bulk structure, together with an iterative algorithm that ensures the non-negativity of the electron density enables the determination of the amplitudes and phases of the surface structure factors contributing to the crystal truncation rods; second, inclusion of these structure factors in an iterative algorithm based on Sayre's equations enables the phasing of the superstructure rods.

Shneerson, Valentin; Fung, Russell; Saldin, Dilano

2003-03-01

155

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

PubMed

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

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

2013-06-15

156

Probing the hydration water diffusion of macromolecular surfaces and interfaces  

NASA Astrophysics Data System (ADS)

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

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

2011-01-01

157

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

2013-10-18

158

Curvilinear All-Atom Multiscale (CAM) Theory of Macromolecular Dynamics  

Microsoft Academic Search

A method is introduced for simulating long timescale macromolecular structural fluctuations and transitions with atomic-scale\\u000a detail. The N-atom Liouville equation for the macromolecule\\/host medium system provides the starting point for the analysis. Order parameters\\u000a characterizing overall macromolecular architecture are demonstrated to be slowly evolving.\\u000a \\u000a \\u000a \\u000a For single-stranded macromolecules, a curvilinear coordinate provides a way to introduce the order parameters. Using a

Z. Shreif; P. Ortoleva

2008-01-01

159

Macromolecular transport in heart valves. I. Studies of rat valves with horseradish peroxidase  

Microsoft Academic Search

The present study aims to experimentally elucidate subtle structural features of the rat valve leaflet and the related nature of macromolecular transport across its endothelium and in its subendothelial space, information necessary to construct a rational theoretical model that can ex- plain observation. After intravenous injection of horseradish peroxidase (HRP), we perfusion- fixed the aortic valve of normal Sprague-Dawley rats

ZHONGQING ZENG; YONGYI YIN; AN-LI HUANG; KUNG-MING JAN; DAVID S. RUMSCHITZKI

2007-01-01

160

Structural cluster analysis of chemical reactions in solution  

NASA Astrophysics Data System (ADS)

We introduce a simple and general approach to the problem of clustering structures from atomic trajectories of chemical reactions in solution. By considering distance metrics which are invariant under permutation of identical atoms or molecules, we demonstrate that it is possible to automatically resolve as distinct structural clusters the configurations corresponding to reactants, products, and transition states, even in presence of atom-exchanges and of hundreds of solvent molecules. Our approach strongly simplifies the analysis of large trajectories and it opens the way to the construction of kinetic network models of activated processes in solution employing the available efficient schemes developed for proteins conformational ensembles.

Gallet, Grégoire A.; Pietrucci, Fabio

2013-08-01

161

Solution Structures of Two Homologous Venom Peptides from Sicarius dolichocephalus  

PubMed Central

We present solution-state NMR structures for two putative venom peptides from Sicarius dolichocephalus. These peptides were identified from cDNA libraries created from venom gland mRNA and then recombinantly expressed. They are the first structures from any species of Sicarius spiders, and the first peptide structures for any haplogyne spiders. These peptides are homologous to one another, and while they have at most only 20% sequence identity with known venom peptides their structures follow the inhibitor cystine knot motif that has been found in a broad range of venom peptides.

Loening, Nikolaus M.; Wilson, Zachary N.; Zobel-Thropp, Pamela A.; Binford, Greta J.

2013-01-01

162

Macromolecular and Dendrimer Based Magnetic Resonance Contrast Agents  

PubMed Central

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

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

2010-01-01

163

Conformational Variability of Solution Nucelar Magnetic Resonance Structures  

Microsoft Academic Search

In structure determination by X-ray crystallography and solution NMR spectroscopy, experimental data are collected as time and ensemble-averages. Thus, in principle, appropriate time and ensemble-averaged models should be used. Refinement of an ensemble of conformers rather than one single structure against the experimental NMR data could, however, result in overfitting the data because of the significantly increased number of parameters.

Alexandre M. J. J. Bonvin; Axel T. Brünger

1995-01-01

164

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

165

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

PubMed Central

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

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

2011-01-01

166

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

167

Macromolecular organization of basement membranes  

Microsoft Academic Search

A considerable variety of basement membrane components, including in particular more than ten laminin isoforms and their novel ? chains (?3, ?4 and ?5), has been characterized in recent studies. The functional properties of these components are increasingly being analyzed by recombinant technologies and by structural studies at atomic resolution, techniques which led to the elucidation of the nidogen-binding epitope

Rupert Timpl

1996-01-01

168

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

169

An analytical solution for approximating simple structure in factor analysis  

Microsoft Academic Search

It is proposed that a satisfactory criterion for an approximation to simple structure is the minimization of the sums of cross-products (across factors) ofsquares of factor loadings. This criterion is completely analytical and yields a unique solution; it requires no plotting, nor any decisions as to the clustering of variables into subgroups. The equations involved appear to be capable only

John B. Carroll

1953-01-01

170

DNA adduct structure-function relationships: comparing solution with polymerase structures.  

PubMed

It has now been nearly two decades since the first solution structures of DNA duplexes covalently damaged by metabolically activated polycyclic aromatic hydrocarbons and amines were determined by NMR. Dozens of such high-resolution structures are now available, and some broad structural themes have been uncovered. It has been hypothesized that the solution structures are relevant to the biochemical processing of the adducts. The structural features of the adducts are considered to determine their mutational properties in DNA polymerases and their repair susceptibilities. In recent years, a number of crystal structures of DNA adducts of interest to our work have been determined in DNA polymerases. Accordingly, it is now timely to consider how NMR solution structures relate to structures within DNA polymerases. The NMR solution structural themes for polycyclic aromatic adducts are often observed in polymerase crystal structures. While the polymerase interactions can on occasion override the solution preferences, intrinsic adduct conformations favored in solution are often manifested within polymerases and likely play a significant role in lesion processing. PMID:18052109

Broyde, Suse; Wang, Lihua; Zhang, Ling; Rechkoblit, Olga; Geacintov, Nicholas E; Patel, Dinshaw J

2007-12-04

171

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

2012-09-18

172

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

173

Macromolecular Crystallization with Microfluidic Free-Interface Diffusion  

SciTech Connect

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

Segelke, B

2005-02-24

174

Scientific Benchmarks for Guiding Macromolecular Energy Function Improvement  

PubMed Central

Accurate energy functions are critical to macromolecular modeling and design. We describe new tools for identifying inaccuracies in energy functions and guiding their improvement, and illustrate the application of these tools to improvement of the Rosetta energy function. The feature analysis tool identifies discrepancies between structures deposited in the PDB and low energy structures generated by Rosetta; these likely arise from inaccuracies in the energy function. The optE tool optimizes the weights on the different components of the energy function by maximizing the recapitulation of a wide range of experimental observations. We use the tools to examine three proposed modifications to the Rosetta energy function: improving the unfolded state energy model (reference energies), using bicubic spline interpolation to generate knowledge based torisonal potentials, and incorporating the recently developed Dunbrack 2010 rotamer library (Shapovalov and Dunbrack, 2011).

Leaver-Fay, Andrew; O'Meara, Matthew J.; Tyka, Mike; Jacak, Ron; Song, Yifan; Kellogg, Elizabeth H.; Thompson, James; Davis, Ian W.; Pache, Roland A.; Lyskov, Sergey; Gray, Jeffrey J.; Kortemme, Tanja; Richardson, Jane S.; Havranek, James J.; Snoeyink, Jack; Baker, David; Kuhlman, Brian

2013-01-01

175

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

176

Macromolecular crystallization with microfluidic free-interface diffusion.  

PubMed

Fluidigm Corp. released the Topaz 1.96 and 4.96 crystallization chips in the fall of 2004. Topaz 1.96 and 4.96 are the latest evolution of Fluidigm's microfluidics crystallization technologies that enable ultra-low-volume rapid screening for macromolecular crystallization. Topaz 1.96 and 4.96 are similar to each other but represent a major redesign of the Topaz system and have substantially improved ease of automation and ease of use, improved efficiency and even further reduced the amount of material needed. With the release of the new Topaz system, Fluidigm continues to set the standard in low-volume crystallization screening, which is having an increasing impact in the field of structural genomics and more generally in structural biology. It is likely that further optimization and increased utility of the Topaz crystallization system will emerge. It is also probable that further innovation and the emergence of competing technologies will be seen. PMID:15892562

Segelke, Brent

2005-04-01

177

Cooperative Macromolecular Disassembly via the Heat Shock Chaperone Hsc70  

NASA Astrophysics Data System (ADS)

Many essential cellular functions depend on the assembly and disassembly of macromolecular complexes. A general class of protein known as molecular chaperones regulates several of these processes. How can complex protein structure be quickly and efficiently disassembled by the action of a small number of these proteins? One such example is that of clathrin: a ubiquitous coat protein that stabilizes vesicular trafficking by forming a scaffold onto the membrane surface. This scaffold must be removed before the vesicle can deliver its cargo. We report on the cooperative disassembly of yeast-derived GFP-labeled clathrin baskets via its interaction with Hsc70. We exploit the highest signal-to-noise light bursts from single fluorescent baskets transiting a confocal excitation spot to recursively determine the brightness and size distribution of the baskets during the uncoating process. This minimal uncoating system demonstrates the ability of a surprisingly simple protein system to facilitate rapid structural changes through cooperative action.

Puchalla, Jason; Krantz, Kelly; Austin, Robert; Rye, Hays

2008-03-01

178

Scientific benchmarks for guiding macromolecular energy function improvement.  

PubMed

Accurate energy functions are critical to macromolecular modeling and design. We describe new tools for identifying inaccuracies in energy functions and guiding their improvement, and illustrate the application of these tools to the improvement of the Rosetta energy function. The feature analysis tool identifies discrepancies between structures deposited in the PDB and low-energy structures generated by Rosetta; these likely arise from inaccuracies in the energy function. The optE tool optimizes the weights on the different components of the energy function by maximizing the recapitulation of a wide range of experimental observations. We use the tools to examine three proposed modifications to the Rosetta energy function: improving the unfolded state energy model (reference energies), using bicubic spline interpolation to generate knowledge-based torisonal potentials, and incorporating the recently developed Dunbrack 2010 rotamer library (Shapovalov & Dunbrack, 2011). PMID:23422428

Leaver-Fay, Andrew; O'Meara, Matthew J; Tyka, Mike; Jacak, Ron; Song, Yifan; Kellogg, Elizabeth H; Thompson, James; Davis, Ian W; Pache, Roland A; Lyskov, Sergey; Gray, Jeffrey J; Kortemme, Tanja; Richardson, Jane S; Havranek, James J; Snoeyink, Jack; Baker, David; Kuhlman, Brian

2013-01-01

179

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

180

Effect of solute size on transport in structured porous media  

SciTech Connect

The purpose of this work was to investigate the effect of solute size on transport in structured porous media. Miscible displacement experiments were performed with tracers of different sizes (i.e., tritiated water {sup 3}H{sub 2}O), pentafluorobenzoate (PFBA), 2,4-dichlorophenoxyacetic acid (2,4-D), and hydroxypropyl-{beta}-cyclodextrin (HPCD) in aggregated, stratified, and macroporous media. The breakthrough curves exhibited both early breakthrough and tailing, indicative of nonideal transport in these structured media. Comparison of breakthrough curves revealed that the extent of nonideality (e.g., tailing) was HPCD > PFBA, 2,4-D > {sup 3}H{sub 2}O. This behavior is consistent with the impact of solute size on the relative degree of {open_quotes}nonequilibrium{close_quotes} experienced by solutes whose transport is constrained by diffusive mass transfer. The capability of the first-order, dual-porosity mobile-immobile model to represent solute transport in these structured systems was evaluated by comparing independently determined values of the input parameters to values obtained by curve fitting of the experimental measurements. The calculated and optimized values compared quite well for the aggregated and stratified media, but not for the macroporous media. Experiments performed with tracers of different size are useful for characterizing the nature of the porous medium through which transport is occurring. 25 refs., 13 figs., 5 tabs.

Hu, Qinhong; Brusseau, M.L. [Univ. of Arizona, Tucson, AZ (United States)

1995-07-01

181

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

2012-08-21

182

A primer in macromolecular linguistics.  

PubMed

Polymeric macromolecules, when viewed abstractly as strings of symbols, can be treated in terms of formal language theory, providing a mathematical foundation for characterizing such strings both as collections and in terms of their individual structures. In addition this approach offers a framework for analysis of macromolecules by tools and conventions widely used in computational linguistics. This article introduces the ways that linguistics can be and has been applied to molecular biology, covering the relevant formal language theory at a relatively nontechnical level. Analogies between macromolecules and human natural language are used to provide intuitive insights into the relevance of grammars, parsing, and analysis of language complexity to biology. © 2012 Wiley Periodicals, Inc. Biopolymers 99: 203-217, 2013. PMID:23034580

Searls, David B

2012-10-03

183

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

184

Crambin: a direct solution for a 400-atom structure.  

PubMed

The crystal structure of crambin, a 46-residue protein containing the equivalent of approximately 400 fully occupied non-H-atom positions, was originally solved at 1.5 A by exploiting the anomalous scattering of its six S atoms at a single wavelength far removed from the absorption edge of sulfur. The crambin structure has now been resolved without the use of any anomalous-dispersion measurements. The technique employed was an ab initio 'shake-and-bake' method, consisting of a phase-refinement procedure based on the minimal function alternated with Fourier refinement. This method has successfully yielded solutions for a smaller molecule (28 atoms) using 1.2 A data, and a crambin solution was obtained at 1.1 A. PMID:15299333

Weeks, C M; Hauptman, H A; Smith, G D; Blessing, R H; Teeter, M M; Miller R

1995-01-01

185

Rheological and structural properties of active filament solutions.  

SciTech Connect

The rheology and the structure of a dilute semiflexible biofilament solution, like F-actin, interacting via molecular motors is probed by molecular dynamics simulations. Oscillatory external shear is used to measure the storage and loss moduli as a function of motor activity in a range of frequencies and for low shear rates. The overall effect of the motor activity on the rheological properties is interpreted as an increase of the temperature, with the effective temperature proportional to the density of motors. However, the effect of motors on the structural properties of the solution, such as the orientation correlation function, is opposite: the motors drastically increase the orientation correlation length whereas thermal fluctuations decrease it.

Ziebert, F.; Aranson, I. S.; Materials Science Division

2008-01-01

186

Structures and stability of salt-bridge in aqueous solution.  

PubMed

Structures and stability of salt-bridges in aqueous solutions were investigated using a complex formed from the guanidinium (Gdm+) and formate (FmO-) ions as a model system. The Test-particle model (T-model) potentials to describe the interactions in the Gdm+-H2O, FmO(-)-H2O and Gdm+-FmO- complexes were constructed, tested and applied in molecular dynamics (MD) simulations of the aqueous solutions at 298 K. The three-dimensional structures and energetic of the hydrogen bond (H-bond) networks of water in the first hydration shells of the Gdm+ and FmO- ions, as well as the Gdm+-FmO- complex, were visualized and analyzed using various probability distribution (PD) maps. The structures of the average potential energy landscapes at the H-bond networks were employed to characterize the stability and dynamic behavior of water molecules in the first hydration shells of the solutes. It was observed that water molecules in the first hydration shell of the close-contact Gdm+-FmO- complex form associated H-bond networks, which introduce a net stabilization effect to the ion-pair, whereas those in the interstitial H-bond network destabilize and break the solvent-separated Gdm+-FmO- complex. The present results showed that, in order to provide complete insights into the structures and stability of ion-pairs in aqueous solutions, explicit water molecules have to be included in the model calculations. PMID:15935545

Sagarik, Kritsana; Chaiyapongs, Supaporn

2005-09-01

187

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

188

Understanding the defect structure of solution grown zinc oxide  

SciTech Connect

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

Liew, Laura-Lynn [Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A-STAR), 3 Research Link, Singapore 117602 (Singapore); School of Materials Science and Engineering, Nanyang Technological University, Block N4.1 Nanyang Avenue, Singapore 639798 (Singapore); Sankar, Gopinathan, E-mail: g.sankar@ucl.ac.uk [Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ (United Kingdom); Handoko, Albertus D. [Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A-STAR), 3 Research Link, Singapore 117602 (Singapore); Goh, Gregory K.L., E-mail: g-goh@imre.a-star.edu.sg [Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A-STAR), 3 Research Link, Singapore 117602 (Singapore); School of Materials Science and Engineering, Nanyang Technological University, Block N4.1 Nanyang Avenue, Singapore 639798 (Singapore); Kohara, Shinji [Japan Synchrotron Radiation Research Institute (JASRI), Mikazuki, Sayo, Hyogo 679-5198 (Japan)

2012-05-15

189

Multifunctional structure solutions for Ultra High Precision (UHP) machine tools  

Microsoft Academic Search

This paper aims to study innovative structure solutions for Ultra High Precision (UHP) Machine Tools (MT) within machining applications at micro\\/mesoscale level (10–10000?m range). There are many aspects that can affect the accuracy of UHP machining performance. The most important issues are related to the static, dynamic and thermal behaviour of the machines. This paper shows a complete study and

F. Aggogeri; A. Merlo; M. Mazzola

2010-01-01

190

Effect of solute size on transport in structured porous media  

Microsoft Academic Search

The purpose of this work was to investigate the effect of solute size on transport in structured porous media. Miscible displacement experiments were performed with tracers of different sizes [i.e., tritiated water (3H2O), pentafluorobenzoate (PFBA), 2,4-dichlorophenoxyacetic acid (2,4-D), and hydroxypropyl-beta-cyclodextrin (HPCD)] in aggregated, stratified, and macroporous media. The breakthrough curves exhibited both early breakthrough and tailing, indicative of nonideal transport

Qinhong Hu; Mark L. Brusseau

1995-01-01

191

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

192

Solution structure of folic acid. Molecular mechanics and NMR investigation  

NASA Astrophysics Data System (ADS)

The structure of folic acid in solution was investigated by nuclear magnetic resonance (NMR) and theoretical calculations. Dynamical information and geometrical constraints were obtained by carbon-13 relaxation study, homo-nuclear NOESY spectra and hetero-nuclear 1H- 13C NOE experiments. This set of experimental data was used for the molecular mechanics and molecular dynamic calculations. The accuracy of the final structure was established by the RNMR factor, which was calculated comparing the experimental NOESY cross-peaks intensities and the corresponding values simulated by using the complete relaxation matrix analysis (CORMA) approach.

Bonechi, C.; Donati, A.; Lampariello, R.; Martini, S.; Picchi, M. P.; Ricci, M.; Rossi, C.

2004-06-01

193

Quantitative phase determination for macromolecular crystals using stereoscopic multibeam imaging.  

PubMed

Without invoking anomalous dispersion and heavy-atom derivatives, it is demonstrated that it is possible to directly determine the phases of a large number of reflections collected in a short time from macromolecular crystals using a stereoscopic oscillation-crystal imaging technique, in a multibeam diffraction geometry, where two crystallographic axes in opposite directions are employed as the rotation axes. The intensity profiles (distributions) of the diffraction spots versus the varying tilt Bragg angle of the rotation axis in the two stereoscopically related images yield quantitative phase information. Many multiple diffraction profiles of tetragonal lysozyme and an unknown protein structure are obtained at the rate of 100 profiles per 30 min of X-ray exposure. PMID:10927303

Chang; Chao; Huang; Jean; Sheu; Liang; Chien; Chen; Yuan

1999-09-01

194

Enhanced macromolecular diffusion in brain extracellular space in mouse models of vasogenic edema measured by cortical surface photobleaching  

Microsoft Academic Search

Diffusion of solutes and macromolecules in brain extracellular space (ECS) is important for normal brain function and efficient drug delivery, and is thought to be impaired in edematous brain. Here we measured the diffusion of an inert macromolecular fluorescent marker (FITC- dextran, 70 kDa) in the ECS by fluorescence recovery after photobleaching after staining the exposed cerebral cortex in vivo.

Marios C. Papadopoulos; Devin K. Binder; A. S. Verkman

2004-01-01

195

Solution structure and thermodynamics of 2',5' RNA intercalation.  

PubMed

As a means to explore the influence of the nucleic acid backbone on the intercalative binding of ligands to DNA and RNA, we have determined the solution structure of a proflavine-bound 2',5'-linked octamer duplex with the sequence GCCGCGGC. This structure represents the first NMR structure of an intercalated RNA duplex, of either backbone structural isomer. By comparison with X-ray crystal structures, we have identified similarities and differences between intercalated 3',5' and 2',5'-linked RNA duplexes. First, the two forms of RNA have different sugar pucker geometries at the intercalated nucleotide steps, yet have the same interphosphate distances. Second, as in intercalated 3',5' RNA, the phosphate backbone angle zeta at the 2',5' RNA intercalation site prefers to be in the trans conformation, whereas unintercalated 2',5' and 3',5' RNA prefer the -gauche conformation. These observations provide new insights regarding the transitions required for intercalation of a phosphodiester-ribose backbone and suggest a possible contribution of the backbone to the origin of the nearest-neighbor exclusion principle. Thermodynamic studies presented for intercalation of both structural RNA isomers also reveal a surprising sensitivity of intercalator binding enthalpy and entropy to the details of RNA backbone structure. PMID:19309071

Horowitz, Eric D; Lilavivat, Seth; Holladay, Benjamin W; Germann, Markus W; Hud, Nicholas V

2009-04-29

196

Kinetic analysis of macromolecular interactions using surface plasmon resonance biosensors  

Microsoft Academic Search

Surface plasmon resonance based biosensors are being used to define the kinetics of a wide variety of macromolecular interactions. As the popularity of this approach grows, experimental design and data analysis methods continue to evolve. These advances are making it possible to accurately define the assembly mechanisms and rate constants associated with macromolecular interactions.

David G Myszka

1997-01-01

197

Surface structure solution by X-ray diffraction: structure completion with positivity and atomicity constraints  

NASA Astrophysics Data System (ADS)

We propose a method for the solution of surface structures from X-ray diffraction based on the phasing of measured structure factor amplitudes in two stages. First, incorporation of calculated amplitudes and phases of the structure factors of the known underlying bulk structure, together with an iterative algorithm that ensures the positivity of the electron density enables the determination of the amplitudes and phases of the surface structure factors contributing to the crystal truncation rods. Second, inclusion of these structure factors in an iterative algorithm based on Sayre's equations enables the phasing of the superstructure rods.

Saldin, D. K.; Shneerson, V. L.; Fung, R.

2003-08-01

198

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

199

Conformational equilibria of alkanes in aqueous solution: relationship to water structure near hydrophobic solutes.  

PubMed Central

Conformational free energies of butane, pentane, and hexane in water are calculated from molecular simulations with explicit waters and from a simple molecular theory in which the local hydration structure is estimated based on a proximity approximation. This proximity approximation uses only the two nearest carbon atoms on the alkane to predict the local water density at a given point in space. Conformational free energies of hydration are subsequently calculated using a free energy perturbation method. Quantitative agreement is found between the free energies obtained from simulations and theory. Moreover, free energy calculations using this proximity approximation are approximately four orders of magnitude faster than those based on explicit water simulations. Our results demonstrate the accuracy and utility of the proximity approximation for predicting water structure as the basis for a quantitative description of n-alkane conformational equilibria in water. In addition, the proximity approximation provides a molecular foundation for extending predictions of water structure and hydration thermodynamic properties of simple hydrophobic solutes to larger clusters or assemblies of hydrophobic solutes.

Ashbaugh, H S; Garde, S; Hummer, G; Kaler, E W; Paulaitis, M E

1999-01-01

200

Structure and electronic properties of a benzene-water solution  

NASA Astrophysics Data System (ADS)

Electronic properties of benzene in water were investigated by a sequential quantum mechanical/molecular dynamics approach. Emphasis was placed on the analysis of the structure, polarization effects, and ionization spectrum. By adopting a polarizable model for both benzene and water the structure of the benzene-water solution is in good agreement with data from first principles molecular dynamics. Further, strong evidence that water molecules acquire enhanced orientational order near the benzene molecule is found. Upon hydration, the quadrupole moment of benzene is not significantly changed in comparison with the gas-phase value. We are also reporting results for the dynamic polarizability of benzene in water. Our results indicate that the low energy behaviour of the dynamic polarizability of gas-phase and hydrated benzene is quite similar. Outer valence Green's function calculations for benzene in liquid water show a splitting of the gas-phase energy levels associated with the 1e1g(?), 2e2g, and 2e1u orbitals upon hydration. Lifting of the orbitals degeneracy and redshift of the outer valence bands is related to symmetry breaking of the benzene structure in solution and polarization effects from the surrounding water molecules.

Mateus, Margarida P. S.; Galamba, Nuno; Cabral, Benedito J. Costa

2012-01-01

201

Integral equation theory for the structure of DNA solutions  

NASA Astrophysics Data System (ADS)

The static structure of solutions of DNA fragments is investigated using integral equation theory. The solution is modeled as a four-component system with DNA molecules, bound counterions, free counterions, and coions, all of which are treated explicitly. Each DNA fragment is modeled as a shish-kebab chain with three kinds of sites, i.e., charged sites, neutralized (protonated) sites, and sites with bound counterions. The partial structure factors are obtained using a generalization of the polymer reference interaction model. The undetermined parameters in the model, namely the fraction of protonated and bound sites, are obtained by fitting theoretical predictions for the polymer-polymer and polymer-counterions structure factors to experimental data. It is found that a large majority of counterions is localized near the DNA molecules due to counterions binding and protonation. The bound counterions make a dominant contribution to the total scattering from counterion species. The best fit is obtained when each DNA molecule contains about 22% protonated sites and 53% counterion occupied sites, i.e., the effective DNA charge fraction is about 0.25. This DNA charge fraction is consistent with electrospray ionization and DNA titration experiments.

Shew, Chwen-Yang; Yethiraj, Arun

2002-03-01

202

Three-dimensional structure of interleukin 8 in solution  

SciTech Connect

The solution structure of the interleukin 8 (IL-8) dimer has been solved by nuclear magnetic resonance (NMR) spectroscopy and hybrid distance geometry-dynamical simulated annealing calculations. The structure determination is based on a total of 1,880 experimental distance restraints (of which 82 are intersubunit) and 362 torsion angle restraints (comprising {phi}, {psi}, and {chi}{sub 1} torsion angles). A total of 30 simulated annealing structures were calculated, and the atomic rms distribution about the mean coordinate positions (excluding residues 1-5 of each subunit) is 0.41 {plus minus} 0.08 {angstrom} for the backbone atoms and 0.90 {plus minus} 0.08 {angstrom} for all atoms. The three-dimensional solution structure of the IL-8 dimer reveals a structural motif in which two symmetry-related antiparallel {alpha}-helices, approximately 24 {angstrom} long and separated by about 14 {angstrom}, lie on top of six-stranded antiparallel {beta}-sheet platform derived from two three-stranded Greek keys, one from each monomer unit. The general architecture is similar to that of the {alpha}1/{alpha}2 domains of the human class I histocompatibility antigen HLA-A2. It is suggested that the two {alpha}-helices form the binding site for the cellular receptor and that the specificity of IL-8, as well as that of a number of related proteins involved in cell-specific chemotaxis, mediation of cell growth, and the inflammatory response, is achieved by the distinct distribution of charged and polar residues at the surface of the helices.

Clore, G.M.; Appella, E.; Gronenborn, A.M. (National Institutes of Health, Bethesda, MD (USA)); Yamada, Masaki (National Cancer Institute, Frederick, MD (USA)); Matsushima, Kouji (Dainippon Pharmaceutical Company, Osaka (Japan))

1990-02-20

203

Solution structure of the luzopeptin-DNA complex  

SciTech Connect

The luzopeptin-d(C-A-T-G) complex (1 drug/duplex) has been generated in aqueous solution and its structure characterized by a combined application of two-dimensional NMR experiments and molecular dynamics calculations. Once equivalent of luzopeptin binds to the self-complementary tetranucleotide duplex with the 2-fold symmetry of the antitumor agent and the DNA oligomer retained on complex formation. The authors have assigned the exchangeable and nonexchangeable proton resonances of luzopeptin and the d(C-A-T-G) duplex in the complex and identified the intermolecular proton-proton NOEs that define the alignment of the antitumor agent at its binding site in duplex DNA. The analysis was greatly aided by a large number of intermolecular NOEs involving exchangeable protons on both the luzopeptin and the DNA in the complex. The formation of cis peptide bonds for luzopeptin in the complex results in an increased separation of the long sides of the rectangular cyclic depsipeptide backbone and reorients in the glycine amide proton so that it can form an intermolecular hydrogen bond with the 2-carbonyl of T3 in the complex. This observation explains, in part, the requirement for Watson-Crick A{center dot}T pairs to be sandwiched between the quinolines at the bisintercalation site in the luzopeptin-DNA complex. The NMR studies on the luzopeptin-d(C-A-T-G) complex unequivocally establish that antitumor agents can undergo conformational transitions on complex formation with DNA, and it is the conformation of the drug in the complex that should serve as the starting point for drug design studies. The above structural details on the solution structure of the luzopeptin-DNA complex also explain the sequence selectivity of luzopeptin for bisintercalation at d(C-A){center dot}d(T-G) steps in the d(C-A-T-G) duplex in solution.

Zhang, Xiaolu; Patel, D.J. (Columbia Univ., New York, NY (USA))

1991-04-23

204

Functional role of polyhydroxy compounds on protein structure and thermal stability studied by circular dichroism spectroscopy  

Microsoft Academic Search

Polyhydroxy compounds such as cyclitols, acyclic polyols and sugars are produced by a wide variety of organisms under stressful conditions in order to protect macromolecular structure. Plants undergoing abiotic stresses like heat and dehydration accumulate enormous amounts of polyhydroxy compounds (up to 400mM) in their cellular tissues. Not only do they serve as osmoprotectants (“compatible solutes”), they also protect membrane

Martina Ortbauer; Marianne Popp

2008-01-01

205

Macromolecular crowding fails to fold a globular protein in cells  

PubMed Central

Proteins perform their function in cells where macromolecular solutes reach concentrations of >300 g/L and occupy >30% of the volume. The volume excluded by these macromolecules will stabilize globular proteins because the native state occupies less space than the denatured state. Theory predicts that crowding can increase the ratio of folded to unfolded protein by a factor of 100, amounting to 3 kcal/mol of stabilization at room temperature. We tested the idea that volume exclusion dominates the crowding effect in cells with a variant of protein L, a 7-kDa globular protein with seven lysine residues replaced by glutamic acids. Eighty-four percent of the variant molecules populate the denatured state in dilute buffer at room temperature, compared to 0.1% for the wild-type protein. We then used in-cell nuclear magnetic resonance spectroscopy to show that the cytoplasm of Escherichia coli does not overcome even this modest (~1 kcal/mol) free energy deficit. The data are consistent with the idea that non-specific interactions between cytoplasmic components can overcome the excluded volume effect. Evidence for these interactions is provided by the observation that adding simple salts folds the variant in dilute solution, but increasing the salt concentration inside E. coli does not fold the protein. Our data are consistent with other studies of protein stability in cells, and suggest that stabilizing excluded volume effects, which must be present under crowded conditions, can be ameliorated by non-specific interactions between cytoplasmic components.

Schlesinger, Alexander P.; Wang, Yaqiang; Tadeo, Xavier; Millet, Oscar; Pielak, Gary J.

2011-01-01

206

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

207

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

208

Amyloid-? peptide structure in aqueous solution varies with fragment size  

NASA Astrophysics Data System (ADS)

Various fragment sizes of the amyloid-? (A?) peptide have been utilized to mimic the properties of the full-length A? peptide in solution. Among these smaller fragments, A?16 and A?28 have been investigated extensively. In this work, we report the structural and thermodynamic properties of the A?16, A?28, and A?42 peptides in an aqueous solution environment. We performed replica exchange molecular dynamics simulations along with thermodynamic calculations for investigating the conformational free energies, secondary and tertiary structures of the A?16, A?28, and A?42 peptides. The results show that the thermodynamic properties vary from each other for these peptides. Furthermore, the secondary structures in the Asp1-Lys16 and Asp1-Lys28 regions of A?42 cannot be completely captured by the A?16 and A?28 fragments. For example, the ?-sheet structures in the N-terminal region of A?16 and A?28 are either not present or the abundance is significantly decreased in A?42. The ?-helix and ?-sheet abundances in A?28 and A?42 show trends - to some extent - with the potential of mean forces but no such trend could be obtained for A?16. Interestingly, Arg5 forms salt bridges with large abundances in all three peptides. The formation of a salt bridge between Asp23-Lys28 is more preferred over the Glu22-Lys28 salt bridge in A?28 but this trend is vice versa for A?42. This study shows that the Asp1-Lys16 and Asp1-Lys28 regions of the full length A?42 peptide cannot be completely mimicked by studying the A?16 and A?28 peptides.

Wise-Scira, Olivia; Xu, Liang; Kitahara, Taizo; Perry, George; Coskuner, Orkid

2011-11-01

209

Nitric Oxide Release Part I. Macromolecular Scaffolds  

PubMed Central

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

Riccio, Daniel A.; Schoenfisch, Mark H.

2012-01-01

210

Macromolecular recognition and macroscopic interactions by cyclodextrins.  

PubMed

Herein macromolecular recognition by cyclodextrins (CDs) is summarized. Recognition of macromolecules by CDs is classified as main-chain recognition or side-chain recognition. We found that CDs form inclusion complexes with various polymers with high selectivity. Polyrotaxanes in which many CDs are entrapped in a polymer chain were prepared. Tubular polymers were prepared from the polyrotaxanes. CDs were found to recognize side-chains of polymers selectively. CD host polymers were found to form gels with guest polymers in water. These gels showed self-healing properties. When azobenzene was used as a guest, the gel showed sol-gel transition by photoirradiation. When ferrocene was used, redox-responsive gels were obtained. Macroscopic self-assembly through molecular recognition has been discovered. Photoswitchable gel association and dissociation have been observed. PMID:23868461

Harada, Akira; Takashima, Yoshinori

2013-07-19

211

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

212

Solution structure of the core SMN-Gemin2 complex  

PubMed Central

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

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

2012-01-01

213

Solution structure of the core SMN-Gemin2 complex.  

PubMed

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

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

2012-08-01

214

DNA-functionalized gold nanoparticles in macromolecularly crowded polymer solutions.  

PubMed

DNA-functionalized gold nanoparticles (AuNPs) are one of the most commonly used reagents in nanobiotechnology. They are important not only for practical applications in analytical chemistry and drug delivery, but also for fundamental understanding of nanoscience. For biological samples such as blood serum or for intracellular applications, the effects of crowded cellular proteins and nucleic acids need to be considered. The thermodynamic effect of crowding is to induce nanoparticle aggregation. But before such aggregation can take place, there might also be a depletion repulsive barrier. Polyethylene glycol (PEG) is one of the most frequently used polymers to mimic the crowded cellular environment. We show herein that while DNA-functionalized AuNPs are very stable in buffer (e.g., no PEG) and citrate-capped AuNPs are very stable in PEG, DNA-functionalized AuNPs are unstable in PEG and are easily aggregated. Although such aggregation in PEG is mediated by DNA, no sharp melting transition typical for DNA-linked AuNPs is observed. We attribute this broad melting to depletion force instead of DNA base pairing. The effects of PEG molecular weight, concentration and temperature have been studied in detail and we also find an interesting PEG phase separation and AuNP partition into the water-rich phase at high temperature. PMID:23113659

Shin, Jeehae; Zhang, Xu; Liu, Juewen

2012-11-06

215

Hydration structure of salt solutions from ab initio molecular dynamics.  

PubMed

The solvation structures of Na(+), K(+), and Cl(-) ions in aqueous solution have been investigated using density functional theory (DFT) based Car-Parrinello (CP) molecular dynamics (MD) simulations. CPMD trajectories were collected for systems containing three NaCl or KCl ion pairs solvated by 122 water molecules using three different but commonly employed density functionals (BLYP, HCTH, and PBE) with electron correlation treated at the level of the generalized gradient approximation (GGA). The effect of including dispersion forces was analyzed through the use of an empirical correction to the DFT-GGA scheme. Special attention was paid to the hydration characteristics, especially the structural properties of the first solvation shell of the ions, which was investigated through ion-water radial distribution functions, coordination numbers, and angular distribution functions. There are significant differences between the present results obtained from CPMD simulations and those provided by classical MD based on either the CHARMM force field or a polarizable model. Overall, the computed structural properties are in fair agreement with the available experimental results. In particular, the observed coordination numbers 5.0-5.5, 6.0-6.4, and 6.0-6.5 for Na(+), K(+), and Cl(-), respectively, are consistent with X-ray and neutron scattering studies but differ somewhat from some of the many other recent computational studies of these important systems. Possible reasons for the differences are discussed. PMID:23298049

Bankura, Arindam; Carnevale, Vincenzo; Klein, Michael L

2013-01-01

216

Synthesis and Structure Solution of Zeolite SSZ-65  

SciTech Connect

This report describes the synthesis and structure solution of the new zeolite SSZ-65. SSZ-65 may be prepared as either a borosilicate (Si52.5B1.5O108) or an aluminosilicate using 1-[1-(4-chloro-phenyl)-cyclopropylmethyl]-1-ethyl-pyrrolidinium as a structure-directing agent. The structure of SSZ-65 was determined with the FOCUS Fourier recycling method. The framework of SSZ-65 possesses a two-dimensional system of intersecting 12-ring channels with pore apertures of 6.9 Angstroms x 5.9 Angstroms . The topological symmetry of SSZ-65 is P6/mmm, but improvements in the Rietveld refinement of the powder diffraction data are obtained in space group P6/m (a = 16.8009(2) Angstroms and c = 12.6154(1) Angstroms ). The agreement values improve from Rwp = 0.116, Rp = 0.094, and R(F2) = 0.142 in P6/mmm to Rwp = 0.103, Rp = 0.085, and R(F2) = 0.092 in P6/m.

Elomari,S.; Burton, A.; Ong, K.; Pradhan, A.; Chan, I.

2007-01-01

217

Hydration structure of salt solutions from ab initio molecular dynamics  

NASA Astrophysics Data System (ADS)

The solvation structures of Na+, K+, and Cl- ions in aqueous solution have been investigated using density functional theory (DFT) based Car-Parrinello (CP) molecular dynamics (MD) simulations. CPMD trajectories were collected for systems containing three NaCl or KCl ion pairs solvated by 122 water molecules using three different but commonly employed density functionals (BLYP, HCTH, and PBE) with electron correlation treated at the level of the generalized gradient approximation (GGA). The effect of including dispersion forces was analyzed through the use of an empirical correction to the DFT-GGA scheme. Special attention was paid to the hydration characteristics, especially the structural properties of the first solvation shell of the ions, which was investigated through ion-water radial distribution functions, coordination numbers, and angular distribution functions. There are significant differences between the present results obtained from CPMD simulations and those provided by classical MD based on either the CHARMM force field or a polarizable model. Overall, the computed structural properties are in fair agreement with the available experimental results. In particular, the observed coordination numbers 5.0-5.5, 6.0-6.4, and 6.0-6.5 for Na+, K+, and Cl-, respectively, are consistent with X-ray and neutron scattering studies but differ somewhat from some of the many other recent computational studies of these important systems. Possible reasons for the differences are discussed.

Bankura, Arindam; Carnevale, Vincenzo; Klein, Michael L.

2013-01-01

218

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

2011-12-21

219

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

220

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

2013-10-02

221

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

222

Characterization of Chitin and Chitosan Molecular Structure in Aqueous Solution  

SciTech Connect

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

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

2008-12-01

223

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

224

Solution structure and dynamics of ADF from Toxoplasma gondii  

PubMed Central

Toxoplasma gondii (TgADF) belongs to a functional subtype characterized by strong G-actin sequestering activity and low F-actin severing activity. Among the characterized ADF/cofilin proteins, TgADF has the shortest length and is missing a C-terminal helix implicated in F-actin binding. In order to understand its characteristic properties, we have determined the solution structure of TgADF and studied its backbone dynamics from 15N-relaxation measurements. TgADF has conserved ADF/cofilin fold consisting of a central mixed ?-sheet comprised of six ?-strands that are partially surrounded by three ?-helices and a C-terminal helical turn. The high G-actin sequestering activity of TgADF relies on highly structurally and dynamically optimized interactions between G-actin with the G-actin binding surface of TgADF. The equilibrium dissociation constant for TgADF and rabbit muscle G-actin was 23.81 nM, as measured by ITC, which reflects very strong affinity of TgADF and G-actin interactions. The F-actin binding site of TgADF is partially formed, with a shortened F-loop that does not project out of the ellipsoid structure and a C-terminal helical turn in place of the C-terminal helix ?4. Yet, it is more rigid than the typical F-actin binding site of Leishmania donovani cofilin. Experimental observations and structural features do not support the interaction of PIP2 with TgADF, and PIP2 does not affect the interaction of TgADF with G-actin. Overall, this study suggests that conformational flexibility of G-actin binding sites enhances the affinity of TgADF for G-actin, while conformational rigidity of F-actin binding sites of conventional ADF/cofilins is necessary for stable binding to F-actin.

Yadav, Rahul; Pathak, Prem Prakash; Shukla, Vaibhav; Jain, Anupam; Srivastava, Shubhra; Tripathi, Sarita; Pulavarti, S.V.S.R. Krishna; Mehta, Simren; Sibley, L. David; Arora, Ashish

2013-01-01

225

Solution structures of cyclic melanocortin agonists and antagonists by NMR.  

PubMed

The melanocortin receptors are involved in many physiological functions, including pigmentation, sexual function, feeding behavior, and energy homeostasis, making them potential targets for drugs to treat obesity, sexual dysfunction, etc. Understanding the conformational basis of the receptor-ligand interactions is crucial to the design of potent and selective ligands for these receptors. The solution structures of the cyclic melanocortin agonists, partial agonist, and antagonists MTII, VJH085, SHU9119, MK5, and MK9 were determined by two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy at pH 4.5 and 25 degrees C in water (90% H(2)O/10% D(2)O). The overall backbone structures of these cyclic alpha-melanocyte-stimulating hormone (alpha-MSH) analogues around the message sequence (His(6)-D-Phe(7)/D-Nal(2')(7)-Arg(8)-Trp(9)) were similar and reasonably well defined. beta-Turns spanning His(6) and D-Phe(7)/D-Nal(2')(7) were identified in all analogues, and an amphiphilic molecular surface was obtained for the message sequence residues in most structures within the NMR ensembles. The beta-turn, which most closely resembles a type II beta-turn, leads to stacking between the aromatic rings of His(6) and D-Phe(7) in MTII and VJH085. However, no aromatic stacking between His(6) and D-Nal(2')(7) was found in structures of the D-Nal(2')(7)-containing analogues. The difference in the side-chain dispositions of His(6) and D-Nal(2')(7) may be responsible for the reduced potency or antagonist activity of the D-Nal(2')(7)-containing analogues. In addition, our results suggest that the side-chain orientations may also modulate the receptor selectivity. The information found in this study will be useful for the further design of ligands for melanocortin receptors. PMID:14991679

Ying, Jinfa; Kövér, Katalin E; Gu, Xuyuan; Han, Guoxia; Trivedi, Dev B; Kavarana, Malcolm J; Hruby, Victor J

2003-01-01

226

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

227

Dependence of the mobility of molecular probes in cellulose acetate solutions on complexation and the solution structure  

Microsoft Academic Search

The spin echo technique with a magnetic field pulse gradient was used to measure the translational diffusion coefficients D of molecular probes in solutions of cellulose acetates in dimethyl sulfoxide. A linear dependence of coefficient D on the extent of substitution of the cellulose acetate was established and the sensitivity of D to the supermolecular structure of the polymer solution

O. D. Vetrov; A. M. Gladkii; V. A. Daragan; E. É. Il'ina; D. A. Moskalev; V. V. Myasoedova; A. É. Prizment

1990-01-01

228

Developing macromolecular therapeutics: the future drug-of-choice  

Microsoft Academic Search

Macromolecular drugs including peptides, proteins, antibodies, polysaccharides and nucleic acids have been widely used for\\u000a therapy of major diseases such as carcinoma and AIDS as well as cardiovascular and neurodegenerative disorders among other\\u000a medical conditions. Due to their unmatched properties of high selectivity and efficiency, macromolecular drugs have been recognized\\u000a as the drug-of-choice of the future. Since worldwide progress on

Huining He; Weibing Dong; Junbo Gong; Jingkang Wang; Victor C. Yang

2010-01-01

229

Solution structure of the strawberry allergen Fra a 1.  

PubMed

The PR10 family protein Fra a 1E from strawberry (Fragaria x ananassa) is down-regulated in white strawberry mutants, and transient RNAi (RNA interference)-mediated silencing experiments confirmed that Fra a 1 is involved in fruit pigment synthesis. In the present study, we determined the solution structure of Fra a 1E. The protein fold is identical with that of other members of the PR10 protein family and consists of a seven-stranded antiparallel ?-sheet, two short V-shaped ?-helices and a long C-terminal ?-helix that encompass a hydrophobic pocket. Whereas Fra a 1E contains the glycine-rich loop that is highly conserved throughout the protein family, the volume of the hydrophobic pocket and the size of its entrance are much larger than expected. The three-dimensional structure may shed some light on its physiological function and may help to further understand the role of PR10 proteins in plants. PMID:22913709

Seutter von Loetzen, Christian; Schweimer, Kristian; Schwab, Wilfried; Rösch, Paul; Hartl-Spiegelhauer, Olivia

2012-12-01

230

Polydisulfide Based Biodegradable Macromolecular Magnetic Resonance Imaging Contrast Agents  

PubMed Central

Macromolecular Gd(III) complexes are advantageous over small molecular Gd(III) complexes in contrast enhanced magnetic resonance imaging (MRI) because of their prolonged blood circulation and preferential tumor accumulation. However, macromolecular contrast agents have not been approved for clinical applications because of the safety concerns related to their slow body excretion. Polydisulfide Gd(III) complexes have been designed and developed as biodegradable macromolecular MRI contrast agents to alleviate the concerns by facilitating the clearance of Gd(III) complexes from the body. These agents initially behave as macromolecular agents and result in superior contrast enhancement in the vasculature and tumor tissues. They can then be readily degraded in vivo into small molecular chelates that can rapidly excrete from the body via renal filtration after the MRI examinations. Various polydisulfide Gd(III) complexes have been prepared as biodegradable macromolecular MRI contrast agents. These agents have resulted in strong contrast enhancement in the vasculature and tumor tissue in animal models with minimal long-term tissue accumulation comparable to small molecular contrast agents. Polydisulfide Gd(III) complexes are promising for further clinical development as safe and effective biodegradable macromolecular MRI contrast agents for cardiovascular and cancer imaging. The review summarizes the chemistry and properties of polydisulfide Gd(III) complexes.

Lu, Zheng-Rong; Wu, Xueming

2011-01-01

231

Present status of SPring-8 macromolecular crystallography beamlines  

SciTech Connect

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

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

2010-06-23

232

Effect of carbon dioxide on rheological properties and structure of polyacrylamide solutions  

Microsoft Academic Search

The effect of CO2 on rheological properties and structure of polyacrylamide solutions was studied as a function of pressure, treating time, polymer type and presence of inorganic electrolytes and natural formation rocks. It was found that the serious deterioration of the solution viscosity can be attributed mostly to the change of the solution structure, while the actual molecular degradation plays

I. Lakatos; J. Lakatos-Szabó

1996-01-01

233

Factor Structure of Rational Vacuum Metrics and a Generalization of the Tomimatsu-Sato Solutions  

NASA Astrophysics Data System (ADS)

We consider stationary axisymmetric vacuum gravitational fields. We use the factor structure of rational solutions to derive a first order and a second order equation for two functions. From the solutions of those equations the Ernst potential can be found by quadrature. As an application we give a new class of solutions in spherical coordinates which generalize the Tomimatsu-Sato solutions.

Hoenselaers, Cornelius A.

234

Solution Structures of Chemoenzymatically Synthesized Heparin and Its Precursors  

PubMed Central

We report the first chemoenzymatic synthesis of the stable isotope-enriched heparin from a uniformly labeled [13C,15N]N-acetylheparosan (-GlcA(1,4)GlcNAc-) prepared from E. coli K5. Glycosaminoglycan (GAG) precursors and heparin were formed from N-acetylheparosan by the following steps: chemical N-deacetylation and N-sulfonation leading to N-sulfoheparosan (-GlcA(1,4)GlcNS-); enzyme-catalyzed C5-epimerization and 2-O-sulfonation leading to undersulfated heparin (-IdoA2S(1,4)GlcNS-); enzymatic 6-O-sulfonation leading to the heparin backbone (-IdoA2S(1,4)GlcNS6S-); and selective enzymatic 3-O-sulfonation leading to the anticoagulant heparin, containing the GlcNS6S3S residue. Heteronuclear, multidimensional nuclear magnetic resonance spectroscopy was employed to analyze the chemical composition and solution structure of [13C,15N]N-acetylheparosan, precursors, and heparin. Isotopic enrichment was found to provide well-resolved 13C spectra with the high sensitivity required for conformational studies of these biomolecules. Stable isotope-labeled heparin was indistinguishable from heparin derived from animal tissues and is a novel reagent for studying the interaction of heparin with proteins.

Zhang, Zhenqing; McCallum, Scott A.; Xie, Jin; Nieto, Lidia; Corzana, Francisco; Jimenez-Barbero, Jesus; Chen, Miao; Liu, Jian; Linhardt, Robert J.

2009-01-01

235

Structure and solution properties of enzymatically synthesized glycogen.  

PubMed

Recently, a new enzymatic process for glycogen production was developed. In this process, short-chain amylose is used as a substrate for branching enzymes (BE, EC 2.4.1.18). The molecular weight of the enzymatically synthesized glycogen (ESG) depends on the size and concentration of the substrate. Structural and physicochemical properties of ESG were compared to those of natural source glycogen (NSG). The average chain length, interior chain length, and exterior chain length of ESG were 8.2-11.6, 2.0-3.3, and 4.2-7.6, respectively. These values were within the range of variation of NSG. The appearances of both ESG and NSG in solution were opalescent (milky white and slightly bluish). Furthermore, transmission electron microscopy and atomic force microscopy showed that ESG molecules formed spherical particles, and that there were no differences between ESG and NSG. Viscometric analyses also showed the spherical nature of both glycogens. When ESG and NSG were treated with pullulanase, a glucan-hydrolyzing enzyme known to degrade glycogen only on its surface portion, both glycogens were similarly degraded. These analyses revealed that ESG shares similar molecular shapes and surface properties with NSG. PMID:20153852

Kajiura, Hideki; Takata, Hiroki; Kuriki, Takashi; Kitamura, Shinichi

2010-01-28

236

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

237

Canadian Macromolecular Crystallography Facility (CMCF) 08ID-1 status update  

NASA Astrophysics Data System (ADS)

The Canadian Macromolecular Crystallography Facility (CMCF) 08ID-1 beamline at the Canadian Light Source (CLS) is in the later stages of commissioning. The photon source is a small-gap in-vacuum undulator (SGU), which was designed in-house with a support structure and vacuum chamber from RMP of Italy. The undulator magnets were shimmed at the CLS and the SGU was installed in the 2.9 GeV storage ring. The storage ring has had currents up to 300 mA safely injected and stored since its first light in the diagnostic beamline in December of 2003. At these storage ring currents, the 7th harmonic of the SGU will yield a photon flux on the sample at the endstation on the order of ˜5×10 at 12 keV. The overall design of the beamline includes white beam slits, indirectly cryo-cooled first crystal of the DCM and sagittally focusing second crystal, and vertically focussing ULE mirror. The endstation of the beamline is innovative and robust, and was manufactured by ACCEL according to CLS specifications. The beamline controls, are being developed based on EPICS, and complemented with a user-friendly interface. The scientific goal of the 08ID-1 beamline is to operate a protein crystallography MAD beamline suitable for studying small crystals and crystals with large unit cells.

Duffy, Alan; Fodje, Michel; Berg, Russ; Grochulski, Pawel

2007-11-01

238

Macromolecular assemblies based on coupled inclusion complex and electrostatic interactions.  

PubMed

Macromolecular assemblies are elaborated by mixing beta-cyclodextrin-containing polymer (polybetaCD), dextran sulfate polyanion (NaDxS), and cationic amphiphiles which are adamantane derivatives (Ada1 or Ada2) in aqueous medium. These components are assembled via coupled inclusion complex interactions (adamantyl group with cyclodextrin cavity) and electrostatic attractive interactions (positive charges of Ada with negative charge of NaDxS). The structural properties are studied by viscometry and small angle neutron scattering. Ternary aggregates with larger size and lower compacities are observed as the cation concentration is increased, until phase separation occurs. The results are in good agreement with a core-shell association mechanism, the core being made of one polybetaCD chain, the shell of NaDxS chains, and the Ada amphiphiles being distributed more or less homogeneously inside the cyclodextrin cavities. The nature of the Ada counterions has a strong influence on the association as Ada1 with I(-) counterions give smaller and less compact aggregates than Ada2 with Br(-) counterions. PMID:17025367

Burckbuchler, Virginie; Boutant, Valérie; Wintgens, Véronique; Amiel, Catherine

2006-10-01

239

Comparison of the crystal and solution structures of two RNA oligonucleotides.  

PubMed Central

Until recently, there were no examples of RNAs whose structures had been determined by both NMR and x-ray crystallography, and thus there was no experimental basis for assessing the accuracy of RNA solution structures. A comparison of the solution and the crystal structures of two RNAs is presented, which demonstrates that NMR can produce solution structures that resemble crystal structures and thus validates the application to RNA of a methodology developed initially for the determination of protein conformations. Models for RNA solution structures are appreciably affected by the parameters used for their refinement that describe intramolecular interactions. For the RNAs of interest here, the more realistic those parameters, the greater the similarity between solution structures and crystal structures.

Rife, J P; Stallings, S C; Correll, C C; Dallas, A; Steitz, T A; Moore, P B

1999-01-01

240

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.

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

2008-09-01

241

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 5h. 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 30min. 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

242

Macromolecular drug delivery: basic principles and therapeutic applications.  

PubMed

Macromolecular drugs hold great promise as novel therapeutics of several major disorders, such as cancer and cardiovascular disease. However, their use is limited by lack of efficient, safe, and specific delivery strategies. Successful development of such strategies requires interdisciplinary collaborations involving researchers with expertise on e.g., polymer chemistry, cell biology, nano technology, systems biology, advanced imaging methods, and clinical medicine. This poses obvious challenges to the scientific community, but also provides opportunities for the unexpected at the interface between different disciplines. This review summarizes recent studies of macromolecular delivery that should be of interest to researchers involved in macromolecular drug synthesis as well as in vitro and in vivo drug delivery studies. PMID:19475521

Belting, Mattias; Wittrup, Anders

2009-05-28

243

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

244

Data structures for on-line updating of matroid intersection solutions  

Microsoft Academic Search

Matroid intersection problems are considered in which one of the matroids is a partition matroid specifying that exactly q elements in the solution must be red, and the rest green. A characterization is presented for how the solution changes when one element changes in cost. Data structures are given for maintaining the solutions to several such problems online under the

Greg N. Frederickson; Mandayam A. Srinivast

1984-01-01

245

Unexpected effects of macromolecular crowding on protein stability.  

PubMed

Most theories about macromolecular crowding focus on two ideas: the macromolecular nature of the crowder and entropy. For proteins, the volume excluded by the crowder favors compact native states over expanded denatured states, enhancing protein stability by decreasing the entropy of unfolding. We tested these ideas with the widely used crowding agent Ficoll-70 and its monomer, sucrose. Contrary to expectations, Ficoll and sucrose have approximately the same stabilizing effect on chymotrypsin inhibitor 2. Furthermore, the stabilization is driven by enthalpy, not entropy. These results point to the need for carefully controlled studies and more sophisticated theories for understanding crowding effects. PMID:23167542

Benton, Laura A; Smith, Austin E; Young, Gregory B; Pielak, Gary J

2012-11-27

246

Solvent effects on morphology and crystal structure of solution-grown organic crystals  

NASA Astrophysics Data System (ADS)

Based on the measured solubility data of acenaphthene, fluoranthene and pyrene in six halogen derivative solvents, the solutes activity coefficients ((gamma) s) have been determined from Scatchard-Hildebrand solution theory and used as a measure of solute-solvent interactions for determination of observed solvent effect on growth morphology and intrinsic structure of solution grown crystals of these hydrocarbons. The growth morphologies of these crystals have been interpreted on the basis of PBC theory assumptions. Correlation between activity coefficients of the investigated solutes and morphology as well as structure of obtained crystals, are found.

Marciniak, Bernard; Rozycka-Sokolowska, Ewa; Pawliuk, W.

2001-04-01

247

Thermodynamics and structure of nonaqueous solutions of electrolytes  

Microsoft Academic Search

The excess relative partial molar (r.p.m.) entropies ~-~E of the solvent in solutions of NaSCN and NHaSCN in methyl alcohol at temperatures of 11 to 50~ are calculated over the whole range of concentrations. The concentration and temperature dependences are compared with the changes in the same functions in aqueous solutions. The influence of the different natures of the cations

É. P. Prosviryakova; K. P. Mishchenko; G. M. Poltoratskii

1969-01-01

248

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

249

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

2013-10-18

250

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

NASA Astrophysics Data System (ADS)

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.

Bowron, Daniel T.; Díaz Moreno, Sofia

2013-11-01

251

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

252

The effects of macromolecular crowding on the mechanical stability of protein molecules  

Microsoft Academic Search

Macromolecular crowding, a common phenomenon in the cellular environments, can significantly affect the thermodynamic and kinetic properties of proteins. A single-molecule method based on atomic force microscopy (AFM) was used to investigate the effects of macromolecular crowding on the forces required to unfold individual protein molecules. It was found that the mechanical stability of ubiquitin molecules was enhanced by macromolecular

Jian-Min Yuan; Chia-Lin Chyan; Huan-Xiang Zhou; Tse-Yu Chung; Haibo Peng; Guanghui Ping; Guoliang Yang

2008-01-01

253

Protein diffusion and macromolecular crowding in thylakoid membranes.  

PubMed

The photosynthetic light reactions of green plants are mediated by chlorophyll-binding protein complexes located in the thylakoid membranes within the chloroplasts. Thylakoid membranes have a complex structure, with lateral segregation of protein complexes into distinct membrane regions known as the grana and the stroma lamellae. It has long been clear that some protein complexes can diffuse between the grana and the stroma lamellae, and that this movement is important for processes including membrane biogenesis, regulation of light harvesting, and turnover and repair of the photosynthetic complexes. In the grana membranes, diffusion may be problematic because the protein complexes are very densely packed (approximately 75% area occupation) and semicrystalline protein arrays are often observed. To date, direct measurements of protein diffusion in green plant thylakoids have been lacking. We have developed a form of fluorescence recovery after photobleaching that allows direct measurement of the diffusion of chlorophyll-protein complexes in isolated grana membranes from Spinacia oleracea. We show that about 75% of fluorophores are immobile within our measuring period of a few minutes. We suggest that this immobility is due to a protein network covering a whole grana disc. However, the remaining fraction is surprisingly mobile (diffusion coefficient 4.6 +/- 0.4 x 10(-11) cm(2) s(-1)), which suggests that it is associated with mobile proteins that exchange between the grana and stroma lamellae within a few seconds. Manipulation of the protein-lipid ratio and the ionic strength of the buffer reveals the roles of macromolecular crowding and protein-protein interactions in restricting the mobility of grana proteins. PMID:18287489

Kirchhoff, Helmut; Haferkamp, Silvia; Allen, John F; Epstein, David B A; Mullineaux, Conrad W

2008-02-20

254

Structure of entropy solutions: applications to variational problems  

Microsoft Academic Search

Abstract. In this paper, we establish rectifiability of the jump set of an S,?valued conservation law in two space?dimensions. This conservation law is a reformulation of the eikonal equation and is motivated by the singular limit of a class of variational problems. The only assumption on the weak solutions is that the entropy productions are (signed) Radon measures, an assumption

Camillo De Lellis; Felix Otto

2003-01-01

255

Macromolecular assembly: chainmail stabilization of a viral capsid.  

PubMed

The subunits that make up the capsid of a double-stranded DNA phage have been found to be arranged as covalently bonded, interlinked pentamer and hexamer rings. This remarkable 'chainmail' arrangement raises interesting new questions about macromolecular assembly. PMID:9889090

Johnson, J E; Wikoff, W R

256

Impact of synchrotron radiation on macromolecular crystallography: a personal view  

PubMed Central

The introduction of synchrotron radiation sources almost four decades ago has led to a revolutionary change in the way that diffraction data from macromolecular crystals are being collected. Here a brief history of the development of methodologies that took advantage of the availability of synchrotron sources are presented, and some personal experiences with the utilization of synchrotrons in the early days are recalled.

Dauter, Zbigniew; Jaskolski, Mariusz; Wlodawer, Alexander

2010-01-01

257

Macromolecular Assemblage in the Design of a Synthetic AIDS Vaccine  

Microsoft Academic Search

We describe a peptide vaccine model based on the mimicry of surface coat protein of a pathogen. This model used a macromolecular assemblage approach to amplify peptide antigens in liposomes or micelles. The key components of the model consisted of an oligomeric lysine scaffolding to amplify peptide antigens covalently 4-fold and a lipophilic membrane-anchoring group to further amplify noncovalently the

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

1992-01-01

258

New magnetic properties of macromolecular compounds containing conjugated double bonds  

Microsoft Academic Search

It has been shown that macromolecular compounds possessing conjugated double bonds reveal new magnetic properties. In the first place, the presence of a sufficiently developed system of conjugate double bonds produces the phenomenon of “unpairedness” in the basic state of the system, which is manifested in pure spin paramagnetism. It may be suggested that this effect occurs for all molecules

L. A. Blyumenfel'd; A. A. Berlin; A. A. Slinkin; A. E. Kalmanson

1960-01-01

259

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

NASA Astrophysics Data System (ADS)

A program to construct ensembles of biomolecular structures that are consistent with experimental scattering data are described. Specifically, we generate an ensemble of biomolecular structures by varying sets of backbone dihedral angles that are then filtered using experimentally determined restraints to rapidly determine structures that have scattering profiles that are consistent with scattering data. We discuss an application of these tools to predict a set of structures for the HIV-1 Gag protein, an intrinsically disordered protein, that are consistent with small-angle neutron scattering experimental data. We have assembled these algorithms into a program called SASSIE for structure generation, visualization, and analysis of intrinsically disordered proteins and other macromolecular ensembles using neutron and X-ray scattering restraints.

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

2012-02-01

260

Structure of aqueous sodium metaborate solutions: X-ray diffraction study  

NASA Astrophysics Data System (ADS)

A structural analysis of aqueous sodium metaborate solutions (NaBo2 · nH2O, n = 10, 15, 20) at 298 ± 0.5 K by a rapid liquid ?-? X-ray diffractometry with a highly effective X'celerator detector is reported in present paper. The radial distribution functions (RDF) and theoretical partial radial distribution functions for B-O, O-O, Na-O, Na-B, and Na-Na atom pairs were obtained from precisely diffraction data processing. Structure of aqueous sodium metaborate solutions was given through model calculation and described in three different items: hydrated sodium ion, hydrated metaborate ion and ion association. Effects of concentration on the structure of the solutions were discussed in detail. The mechanisms of ion aggregation and the formation of crystal nuclei in the solution are proposed. The results show that a clear picture of the structure of aqueous sodium metaborate solution has been acquired.

Yongquan, Zhou; Chunhui, Fang; Yan, Fang; Fayan, Zhu; Song, Tao; Sha, Xu

2012-08-01

261

Pi sampling: a methodical and flexible approach to initial macromolecular crystallization screening  

PubMed Central

The Pi sampling method is derived from the incomplete factorial approach to macromolecular crystallization screen design. The resulting ‘Pi screens’ have a modular distribution of a given set of up to 36 stock solutions. Maximally diverse conditions can be produced by taking into account the properties of the chemicals used in the formulation and the concentrations of the corresponding solutions. The Pi sampling method has been implemented in a web-based application that generates screen formulations and recipes. It is particularly adapted to screens consisting of 96 different conditions. The flexibility and efficiency of Pi sampling is demonstrated by the crystallization of soluble proteins and of an integral membrane-protein sample.

Gorrec, Fabrice; Palmer, Colin M.; Lebon, Guillaume; Warne, Tony

2011-01-01

262

Reverse engineering chemical structures from molecular descriptors : how many solutions?  

SciTech Connect

Physical, chemical and biological properties are the ultimate information of interest for chemical compounds. Molecular descriptors that map structural information to activities and properties are obvious candidates for information sharing. In this paper, we consider the feasibility of using molecular descriptors to safely exchange chemical information in such a way that the original chemical structures cannot be reverse engineered. To investigate the safety of sharing such descriptors, we compute the degeneracy (the number of structure matching a descriptor value) of several 2D descriptors, and use various methods to search for and reverse engineer structures. We examine degeneracy in the entire chemical space taking descriptors values from the alkane isomer series and the PubChem database. We further use a stochastic search to retrieve structures matching specific topological index values. Finally, we investigate the safety of exchanging of fragmental descriptors using deterministic enumeration.

Brown, William Michael (Sandia National Laboratories, Albuquerque, NM); Martin, Shawn Bryan (Sandia National Laboratories, Albuquerque, NM); Faulon, Jean-Loup Michel

2005-06-01

263

Structure of entropy solutions to the eikonal equation  

Microsoft Academic Search

.   In this paper, we establish rectifiability of the jump set of an S\\u000a 1–valued conservation law in two space–dimensions. This conservation law is a reformulation of the eikonal equation and is\\u000a motivated by the singular limit of a class of variational problems. The only assumption on the weak solutions is that the\\u000a entropy productions are (signed) Radon measures, an assumption which

Camillo De Lellis; Felix Otto

2003-01-01

264

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

265

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

266

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

267

Solution NMR Structure of the 30S Ribosomal Protein S28E From Pyrococcus Horikoshii  

SciTech Connect

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 structure, 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 oligonucleotide/oligosaccharide -barrel (OB) fold.

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

2003-12-01

268

MUFOLD: A new solution for protein 3D structure prediction  

PubMed Central

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

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

2010-01-01

269

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

270

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

Microsoft Academic Search

The solution structure of the bee venom neurotoxin apamin has been determined with a distance geometry program using distance constraints derived from NMR. Twenty embedded structures were generated and refined by using the program DSPACE. After error minimization using both conjugate gradient and dynamics algorithms, six structures had very low residual error. Comparisons of these show that the backbone of

Joseph H. B. Pease; David E. Wemmer

1988-01-01

271

Multiple-bed solution mining of an inclined structure  

SciTech Connect

Solution mining method is disclosed particularly adapted for recovery of potash and the like from multiple beds of relatively thin, inclined strata at substantial depths. Dissolution of each ore strata overlain by an insoluble and impermeable strata takes place through a single borehole in sequential order beginning with the deepest ore strata. Water is injected down a borehole at a predetermined rate and, being much less dense than present brine, flows in an updip direction along the top of the cavity to the forward mining face remote from the drill hole. Loaded, heavy brine flows downdip along the bottom of the cavity to an outflow pipe communicating with the bottom of the cavity.

Higgins, R.S.

1983-12-06

272

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

PubMed

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

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

2012-08-28

273

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

274

Solution structure of chicken liver basic fatty acid binding protein.  

PubMed

Chicken liver basic fatty acid binding protein (Lb-FABP) belongs to the basic-type fatty acid binding proteins, a novel group of proteins isolated from liver of different non mammalian species whose structure is not known. The structure of Lb-FABP has been solved by (1)H NMR. The overall fold of Lb-FABP, common to the other proteins of the family, consists of ten antiparallel beta-strands organised in two nearly ortogonal beta-sheets with two alpha helices closing the protein cavity where small hydrophobic ligands can be bound. The binding specificity of the protein is not known, however, based on the high sequence and structural similarity with an orthologous protein, ileal lipid binding protein, it is suggested that bile acids may be the putative ligands. PMID:12652125

Vasile, Francesca; Ragona, Laura; Catalano, Maddalena; Zetta, Lucia; Perduca, Massimiliano; Monaco, Hugo; Molinari, Henriette

2003-02-01

275

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

276

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.

Lonie, David C.; Zurek, Eva

2012-03-01

277

Imaging Macromolecular Interactions at an Interface  

PubMed Central

Important physiological, pathological, and technological processes occur at continuous and dispersed phase interfaces. Understanding these processes is limited by inability to quantitate molecular events occurring at the interface. To provide a model-independent measurement of protein concentration and mobility at the interface, we employed confocal laser scanning microscopy (CLSM). Fluorescently labeled albumin and fibrinogen were studied singly, pairwise, and with a surfactant, Pluronic F-127, in aqueous droplets. CLSM enables measurement of molecular behaviors manifest as surface inhomogeneity and of biophysical quantities including partitioning between the bulk and the gas-liquid (GL) interface. We conclude that albumin and fibrinogen behave substantially differently at the GL interface, that adsorption from multi-species solutions is fundamentally different than adsorption from solutions of single species, and surfactants can inhibit proteins from occupying the interface.

Lampe, Joshua W.; Liao, Zhengzheng; Dmochowski, Ivan J.; Ayyaswamy, Portonovo S.; Eckmann, David M.

2010-01-01

278

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

279

Mapping functionally important motifs SPF and GGQ of the decoding release factor RF2 to the Escherichia coli ribosome by hydroxyl radical footprinting. Implications for macromolecular mimicry and structural changes in RF2.  

PubMed

The function of the decoding release factor (RF) in translation termination is to couple cognate recognition of the stop codon in the mRNA with hydrolysis of the completed polypeptide from its covalently linked tRNA. For this to occur, the RF must interact with specific A-site components of the active centers within both the small and large ribosomal subunits. In this work, we have used directed hydroxyl radical footprinting to map the ribosomal binding site of the Escherichia coli class I release factor RF2, during translation termination. In the presence of the cognate UGA stop codon, residues flanking the universally conserved (250)GGQ(252) motif of RF2 were each shown to footprint to the large ribosomal subunit, specifically to conserved elements of the peptidyltransferase and GTPase-associated centers. In contrast, residues that flank the putative "peptide anticodon" of RF2, (205)SPF(207), were shown to make a footprint in the small ribosomal subunit at positions within well characterized 16 S rRNA motifs in the vicinity of the decoding center. Within the recently solved crystal structure of E. coli RF2, the GGQ and SPF motifs are separated by 23 A only, a distance that is incompatible with the observed cleavage sites that are up to 100 A apart. Our data suggest that RF2 may undergo gross conformational changes upon ribosome binding, the implications of which are discussed in terms of the mechanism of RF-mediated termination. PMID:12458201

Scarlett, Debbie-Jane G; McCaughan, Kim K; Wilson, Daniel N; Tate, Warren P

2002-11-27

280

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

281

Vibration based structural health monitoring: Wavelet packet transform based solution  

Microsoft Academic Search

One prominent problem for vibration-based structural health monitoring is to extract condition indices which are sensitive to damage and yet insensitive to measurement noise. In this paper, a condition index extraction method based on the wavelet packet transform (WPT) is proposed. This transform leads to the formulation of a novel condition index: wavelet packet signature (WPS). The sensitivity of the

Z. Sun; C.-C. Chang

2007-01-01

282

Alteration of structures of sublayer flow in dilute polymer solutions  

Microsoft Academic Search

THE Toms effect may be assumed to be based on a phenomenon which occurs in the immediate wall layer. Models proposed to explain the effect are, therefore, mostly aimed either at producing an interaction of the molecules with the flow structure (that is, the eddies), or at attributing new rheological properties to the liquid on the basis of the molecules

A. Gyr; A. Mueller

1975-01-01

283

Solution Structural Dynamics of HIV-1 Reverse Transcriptase Heterodimer  

PubMed Central

Crystal structures and simulations suggest that conformational changes are critical for the function of HIV-1 reverse transcriptase. The enzyme is an asymmetric heterodimer of two subunits, p66 and p51. The two subunits have the same N-terminal sequence, with the p51 subunit lacking the C-terminal RNase H domain. We used hydrogen exchange mass spectrometry to probe the structural dynamics of RT. H/D exchange revealed that the fingers and palm subdomains of both subunits form the stable core of the heterodimer. In the crystal structure, the tertiary fold of the p51 subunit is more compact than that of the polymerase domain of the p66 subunit, yet both subunits show similar flexibility. The p66 subunit contains both the polymerase and RNase H catalytic sites. H/D exchange indicated that the RNase H domain of p66 is highly flexible. The ?-sheet ?12–?13–?14 lies at the base of the thumb subdomain of p66, and contains highly conserved residues involved in template/primer binding and NNRTI binding. Using the unique ability of hydrogen exchange mass spectrometry to resolve slowly interconverting species, we found that ?-sheet ?12–?13–?14 undergoes slow cooperative unfolding with a t1/2 of 6.6 s. The H/D exchange results are discussed in relation to existing structural, simulation, and sequence information.

Seckler, James M.; Howard, Kathryn J.; Barkley, Mary D.; Wintrode, Patrick L.

2010-01-01

284

Finite element solution for the structural behavior of a scientific balloon  

Microsoft Academic Search

A finite element solution for the structural behavior of a scientific balloon has been obtained using a non-linear finite element code. The pneumatic skin is modelled by shell elements that are given a small artificial bending stiffness to overcome numerical problems yet the membrane solution remains unaffected. Validation of the analysis approach is provided through strain measurements on a small

W. W. Schur; J. M. Simpson

1993-01-01

285

Influence of structure of aqueous polymer solutions on the Toms effect  

Microsoft Academic Search

The influence of the structural characteristics of dilute polymer solutions on the Toms effect has been investigated with reference to the example of aqueous solutions of polyoxyethylene, containing inorganic salts, and polyvinyl alcohol, characterized by the existence of a supermolecular order.

L. I. Shakhovskaya; T. A. Lemesheva; Yu. G. Kryazhev

1978-01-01

286

EXPLORING THE SOLUTION SPACE OF SEMI STRUCTURED SPATIAL PROBLEMS USING GENETIC ALGORITHMS  

Microsoft Academic Search

The resolution of semi-structured spatial problems often requires consensus building and compromise among stakeholders as they attempt to optimize their own set of criteria. The union of these sets form a criteria space that constrains the set of viable solutions that may be adopted by decision-makers. Knowledge about the criteria space, the solution space, and the relation between the two

David A. Bennett; Greg A. Wade; Marc P. Armstrong

287

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

NASA Astrophysics Data System (ADS)

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

Aller, Robert C.

1984-10-01

288

Exact Solutions and Coherence Structures of Generalized Breor-Kaup Equations  

NASA Astrophysics Data System (ADS)

Using the mapping method based on q-deformed hyperbolic functions, the exact solutions of generalized Breor-Kaup equations are obtained. Based on the solutions, two coherent structures, periodic-branch kink and non-propagating kink, have been obtained. Moreover, one solitonal interaction form, two line solitons interaction on the kink background, has been found.

Zheng, Qiang; Zhang, Xiao-Ping; Ren, Zhong-Zhou

2008-12-01

289

Structure and Dynamics of Aqueous Solutions Next to and Between Membrane Surfaces.  

National Technical Information Service (NTIS)

To investigate structural and dynamical properties of aqueous solutions next to and between surfaces of biological macromolecules, particularly membranes. To understand the role of water in the hydration force acting between the membrane molecules we perf...

M. L. Berkowitz

1997-01-01

290

Structure and Dynamics of Aqueous Solutions Next To and Between Membrane Surfaces.  

National Technical Information Service (NTIS)

The objective of our research is to investigate structural and dynamical properties of aqueous solutions next to and between surfaces of biological macromolecules, particularly membranes. The goal of our research is to understand the molecular origin of t...

M. L. Berkowitz

1990-01-01

291

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

292

Anomalous variations of crystal habits and solution properties in the context of the crystallization medium structure  

NASA Astrophysics Data System (ADS)

The effect of the real structure of solutions on crystallization is one of the basic issues of crystallogenesis, which is also important for resolving problems of genetic mineralogy. The study of the NaNO3-H2O and KNO3-H2O model systems yielded new data on anomalous characteristics of crystal-forming systems, including morphological and kinetic properties of crystals, crystal-solution equilibrium, and physical properties of solutions (light scattering, thermal properties, IR parameters, pH), providing information on the structure of solutions. The internally consistent data confirm the previously suggested variations in structural heterogeneity of solutions related to minor (2-4%) variations in their composition, which result in numerous disturbances of monotonicity (thermal-concentration oscillations) in the liquidus curves of salts. It is shown that these variations can be caused by variable size and composition of crystal hydrate clusters. The experimental data indicate that the effect of the real solution structure on crystal morphology and crystal-solution equilibrium is enhanced in multicomponent systems, including natural crystal-forming systems. Anomalous faceting and habit, zoning, a sectorial structure of crystals, and nonuniform entrapment of admixtures cannot be ruled out in these systems.

Kiryanova, E. V.; Ugolkov, V. L.; Pyankova, L. A.; Filatov, S. K.

2009-12-01

293

Structure of the full-length HCV IRES in solution.  

PubMed

The 5'-untranslated region of the hepatitis C virus genome contains an internal ribosome entry site (IRES) that initiates cap-independent translation of the viral RNA. Until now, the structural characterization of the entire (IRES) remained limited to cryo-electron microscopy reconstructions of the (IRES) bound to different cellular partners. Here we report an atomic model of free full-length hepatitis C virus (IRES) refined by selection against small-angle X-ray scattering data that incorporates the known structures of different fragments. We found that an ensemble of conformers reproduces small-angle X-ray scattering data better than a single structure suggesting in combination with molecular dynamics simulations that the hepatitis C virus (IRES) is an articulated molecule made of rigid parts that move relative to each other. Principal component analysis on an ensemble of physically accessible conformers of hepatitis C virus (IRES) revealed dominant collective motions in the molecule, which may underlie the conformational changes occurring in the (IRES) molecule upon formation of the initiation complex. PMID:23511476

Pérard, Julien; Leyrat, Cédric; Baudin, Florence; Drouet, Emmanuel; Jamin, Marc

2013-01-01

294

Long-range hydrogen-bond structure in aqueous solutions and the vapor-water interface  

NASA Astrophysics Data System (ADS)

There is a considerable disagreement about the extent to which solutes perturb water structure. On the one hand, studies that analyse structure directly only show local structuring in a solute's first and possibly second hydration shells. On the other hand, thermodynamic and kinetic data imply indirectly that structuring occurs much further away. Here, the hydrogen-bond structure of water around halide anions, alkali cations, noble-gas solutes, and at the vapor-water interface is examined using molecular dynamics simulations. In addition to the expected perturbation in the first hydration shell, deviations from bulk behavior are observed at longer range in the rest of the simulation box. In particular, at the longer range, there is an excess of acceptors around halide anions, an excess of donors around alkali cations, weakly enhanced tetrahedrality and an oscillating excess and deficiency of donors and acceptors around noble-gas solutes, and enhanced tetrahedrality at the vapor-water interface. The structuring compensates for the short-range perturbation in water-water hydrogen bonds induced by the solute. Rather than being confined close to the solute, it is spread over as many water molecules as possible, presumably to minimize the perturbation to each water molecule.

Irudayam, Sheeba Jem; Henchman, Richard H.

2012-07-01

295

Adaptive Multiscale Molecular Dynamics of Macromolecular Fluids  

NASA Astrophysics Data System (ADS)

Until now, adaptive atomistic-coarse-grain (A/CG) molecular dynamics simulations have had very limited applicability because the on-the-fly CG?A transformation is problematic for all but those molecules whose CG representation consists of a single particle. Here, we solve this problem by combining a transitional healing region with a rotational dynamics of rigid atomistic fragments in the CG region. Error control is obtained by analysis of the A?CG energy flow. We illustrate the method with adaptive multiscale simulations of liquid hexane and of a dilute polymer solution in a theta solvent.

Nielsen, Steven O.; Moore, Preston B.; Ensing, Bernd

2010-12-01

296

Imaging defects in macromolecular crystals with x-ray topography  

NASA Astrophysics Data System (ADS)

X-ray topography is a well established technique to characterize growth or process induced defects. As a characterization tool for crystal growers X-ray topography is probably the simplest non destructive imaging technique available. However, only recently it has been applied to image growth induced defects in protein crystals.We will discuss the use of white and monochromatic x-ray topography methods in understanding macromolecular growth techniques and diffraction properties. White and monochromatic synchrotron radiation from beamline X26C at the National Synchrotron Light Source (NSLS) at the Brookhaven National Laboratory (BNL) were employed in x-ray topographic studies of different macromolecular systems grown by different techniques. Results show that growth conditions and handling affected the quality of the crystals. A high correlation between crystal quality and diffraction characteristics was observed. Above all x-ray topographic methods proved to be non destructive, at least for the proteins studied, lysozyme, concanavalin and myoglobin.

Stojanoff, V.; Siddons, D. P.

1996-03-01

297

Impact of synchrotron radiation on macromolecular crystallography: a personal view.  

PubMed

The introduction of synchrotron radiation sources almost four decades ago has led to a revolutionary change in the way that diffraction data from macromolecular crystals are being collected. Here a brief history of the development of methodologies that took advantage of the availability of synchrotron sources are presented, and some personal experiences with the utilization of synchrotrons in the early days are recalled. PMID:20567074

Dauter, Zbigniew; Jaskolski, Mariusz; Wlodawer, Alexander

2010-05-14

298

Encapsulation Efficiency and Micellar Structure of Solute-Carrying Block Copolymer Nanoparticles  

PubMed Central

We use discontinuous molecular dynamics (DMD) computer simulation to investigate the encapsulation efficiency and micellar structure of solute-carrying block copolymer nanoparticles as a function of packing fraction, polymer volume fraction, solute mole fraction, and the interaction parameters between the hydrophobic head blocks and between the head and the solute. The encapsulation efficiency increases with increasing polymer volume fraction and packing fraction but decreases with increasing head-head interaction strength. The latter is due to an increased tendency for the solute to remain on the micelle surface. We compared two different nanoparticle assembly methods, one in which the solute and copolymer co-associate and the other in which the copolymer micelle is formed before the introduction of solute. The assembly method does not affect the encapsulation efficiency but does affect the solute uptake kinetics. Both head-solute interaction strength and head-head interaction strength affect the density profile of the micelles; increases in the former cause the solute to distribute more evenly throughout the micelle, while increases in the latter cause the solute to concentrate further from the center of the micelle. We explain our results in the context of a model of drug insertion into micelles formulated by Kumar and Prud’homme; as conditions become more conducive to micelle formation, a stronger energy barrier to solute insertion forms which in turn decreases the encapsulation efficiency of the system.

Woodhead, Jeffrey L.; Hall, Carol K.

2011-01-01

299

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

300

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

301

Investigations on the structure of dimethyl sulfoxide and acetone in aqueous solution.  

PubMed

Aqueous solutions of dimethyl sulfoxide (DMSO) and acetone have been investigated using neutron diffraction augmented with isotopic substitution and empirical potential structure refinement computer simulations. Each solute has been measured at two concentrations-1:20 and 1:2 solute:water mole ratios. At both concentrations for each solute, the tetrahedral hydrogen bonding network of water is largely unperturbed, though the total water molecule coordination number is reduced in the higher 1:2 concentrations. With higher concentrations of acetone, water tends to segregate into clusters, while in higher concentrations of DMSO the present study reconfirms that the structure of the liquid is dominated by DMSO-water interactions. This result may have implications for the highly nonideal behavior observed in the thermodynamic functions for 1:2 DMSO-water solutions. PMID:17994835

McLain, Sylvia E; Soper, Alan K; Luzar, Alenka

2007-11-01

302

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

303

Investigations on the structure of DMSO and acetone in aqueous solution  

SciTech Connect

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

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

2007-01-01

304

Macromolecular Assemblage in the Design of a Synthetic AIDS Vaccine  

NASA Astrophysics Data System (ADS)

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

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

1992-05-01

305

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

306

Crystallization of macromolecular complexes: combinatorial complex crystallization  

Microsoft Academic Search

The usefulness of antibody complexation, as a way of increasing the chances of crystallization needs to be re-evaluated after many antibody complexes have been crystallized and their structure determined. It is somewhat striking that among these, only a small number is a complex with a large protein antigen. The problem is that the effort of raising, cleaving and purifying an

Enrico A Stura; Marc Graille; Jean-Baptiste Charbonnier

2001-01-01

307

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

PubMed Central

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

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

2011-01-01

308

X-ray absorption fine structures of uranyl(V) complexes in a nonaqueous solution.  

PubMed

The structures of three different U(V) complexes, [U(V)O(2)(salophen)DMSO](-), [U(V)O(2)(dbm)(2)DMSO](-), and [U(V)O(2)(saldien)](-), in a dimethyl sulfoxide (DMSO) solution were determined by X-ray absorption fine structure for the first time. PMID:19754101

Takao, Koichiro; Tsushima, Satoru; Takao, Shinobu; Scheinost, Andreas C; Bernhard, Gert; Ikeda, Yasuhisa; Hennig, Christoph

2009-10-19

309

Solution structure of nucleic acids by nuclear magnetic resonance (NMR) spectroscopy  

Microsoft Academic Search

Evidence that dehydration effects and crystal packing effects can alter the global and local structure of nucleic acids in the crystalline state has led to attempts to determine their structure directly in solution. Parameterization of the non-bonded force fields for theoretical methods such as energy minimization and molecular dynamics calculations is incomplete and NMR spectroscopy appears to be the most

1992-01-01

310

The structure and properties of cellulose fibres spun from an anisotropic phosphoric acid solution  

Microsoft Academic Search

The structure and the mechanical properties of a newly developed highmodulus\\/high strength cellulose fibre spun from an anisotropic solution in phosphoric acid are discussed and compared with those of existing regenerated cellulose fibres. The crystal structure of the fibre is of the cellulose II modification, and the highly oriented and crystalline fibres have an initial filament modulus of 44GPa, a

M. G. Northolt; H. Boerstoel; H. Maatman; R. Huisman; J. Veurink; H. Elzerman

2001-01-01

311

Rheological investigation of the structural properties and aging effects in the agarose\\/co-solute mixture  

Microsoft Academic Search

Small deformation dynamic oscillation, large deformation compression and creep testing were carried out to examine the structural properties of agarose in the presence of 50:50 preparations of sucrose and glucose syrup. The content of co-solute varied from 10 to 93% in the mixture. Increasing additions of sugar transform gradually the enthalpic, brittle networks of the polysaccharide to ‘rubbery’ structures of

Marcin Deszczynski; Stefan Kasapis; John R. Mitchell

2003-01-01

312

Macromolecular coal structure as revealed by novel diffusion tests  

SciTech Connect

Experimental studies are reported of diffusion in thin sections of various samples. Data are presented of the transport of methylene chloride, chloroform, pyridine, methyl ethyl ketone, toluene, benzene, methanol, acetone and cyclohexane in coals PSOC 418, 853, and 384. The results are analyzed in terms of solubility parameters and the polar contribution to the solubility. These results are compared to swelling of some of crosslinked poly(methyl methacrylate) by some of these solvents. We have proceeded with a more detailed investigation of the influence of various amines on the transport behavior. Finally, we examine various implications of the mathematical analysis using the diffusion/relaxation model. 2 refs., 34 figs., 4 tabs.

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

1989-01-01

313

Nanoscale Imaging with Resonant Coherent XRays: Extension of Multiple-Wavelength Anomalous Diffraction to Nonperiodic Structures  

Microsoft Academic Search

The methodology of multiple-wavelength anomalous diffraction, widely used for macromolecular structure determination, is extended to the imaging of nonperiodic nanostructures. We demonstrate the solution of the phase problem by a combination of two resonantly recorded coherent scattering patterns at the carbon K edge (285 eV). Our approach merges iterative phase retrieval and x-ray holography approaches, yielding unique and rapid reconstructions.

A. Scherz; D. Zhu; R. Rick; W. F. Schlotter; S. Roy; J. Lüning; J. Stöhr

2008-01-01

314

Cluster structure in urea aqueous solution and it's effect on DNA denature  

NASA Astrophysics Data System (ADS)

The existence of large cluster structure in urea aqueous solution is proved by Small Angle Neutron Scattering (SANS). Our results indicate that urea is a water- structure-breaker, and large urea cluster will be formed when it's concentration is higher than 20 w%. This cluster is very stable, and almost do not change with temperature. The helix-to-coil denaturation transition of DNA was studied with various urea concentrations, to testify the solvent structure influence on this process.

Cheng, He; Han, Charles C.; Hammouda, Boualem

2009-03-01

315

Structure property relations in BiFeO3\\/BaTiO3 solid solutions  

Microsoft Academic Search

BiFeO3, when forming a solid solution with BaTiO3, shows structural transformations over the entire compositional range. Above 70 mole % of BiFeO3 the structure is rhombohedral and below 4 mole %, it is tetragonal. In between the structure is cubic. The ferroelectric TC decreases with increasing composition of BaTiO3 and a relatively small relaxation is observed. Impedance measurements showed a

M. Mahesh Kumar; A. Srinivas; S. V. Suryanarayana

2000-01-01

316

Revealing the structural origin of the redox-Bohr effect: the first solution structure of a cytochrome from Geobacter sulfurreducens.  

PubMed

Gs (Geobacter sulfurreducens) can transfer electrons to the exterior of its cells, a property that makes it a preferential candidate for the development of biotechnological applications. Its genome encodes over 100 cytochromes and, despite their abundance and key functional roles, to date there is no structural information for these proteins in solution. The trihaem cytochrome PpcA might have a crucial role in the conversion of electronic energy into protonmotive force, a fundamental step for ATP synthesis in the presence of extracellular electron acceptors. In the present study, 15N-labelled PpcA was produced and NMR spectroscopy was used to determine its solution structure in the fully reduced state, its backbone dynamics and the pH-dependent conformational changes. The structure obtained is well defined, with an average pairwise rmsd (root mean square deviation) of 0.25 Å (1 Å=0.1 nm) for the backbone atoms and 0.99 Å for all heavy atoms, and constitutes the first solution structure of a Gs cytochrome. The redox-Bohr centre responsible for controlling the electron/proton transfer was identified, as well as the putative interacting regions between PpcA and its redox partners. The solution structure of PpcA will constitute the foundation for studies aimed at mapping out in detail these interacting regions. PMID:21861844

Morgado, Leonor; Paixão, Vítor B; Schiffer, Marianne; Pokkuluri, P Raj; Bruix, Marta; Salgueiro, Carlos A

2012-01-01

317

Analytical solutions for transient and steady state beam loading in arbitrary traveling wave accelerating structures  

SciTech Connect

Analytical solutions are derived for both transient and steady state gradient distributions in the traveling wave (TW) accelerating structures with arbitrary variation of parameters over the structure length. The results of the unloaded and beam loaded cases are presented. Finally, the exact analytical shape of the rf pulse waveform was found in order to apply the transient beam loading compensation scheme during the structure filling time. The obtained theoretical formulas were cross-checked by direct numerical simulations on the CLIC main linac accelerating structure and demonstrated a good agreement. The proposed methods provide a fast and reliable tool for the initial stage of the TW structure analysis.

Lunin, A.; Yakovlev, V.; /Fermilab; Grudiev, A.; /CERN

2011-05-02

318

Solution NMR of large molecules and assemblies†  

PubMed Central

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 the past 10 years, advances in NMR and isotope labeling methods have expanded the range of NMR-tractable targets by at least an order of magnitude. Here we briefly describe the methodological advances that allow NMR spectroscopy of large macromolecules and their complexes, and provide a perspective on the wide range of applications of NMR to biochemical problems.

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

2008-01-01

319

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

PubMed Central

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

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

2013-01-01

320

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

PubMed

The SIBYLS beamline (12.3.1) of the Advanced Light Source at Lawrence Berkeley National Laboratory, supported by the US Department of Energy and the National Institutes of Health, is optimized for both small-angle X-ray scattering (SAXS) and macromolecular crystallography (MX), making it unique among the world's mostly SAXS or MX dedicated beamlines. Since SIBYLS was commissioned, assessments of the limitations and advantages of a combined SAXS and MX beamline have suggested new strategies for integration and optimal data collection methods and have led to additional hardware and software enhancements. Features described include a dual mode monochromator [containing both Si(111) crystals and Mo/B(4)C multilayer elements], rapid beamline optics conversion between SAXS and MX modes, active beam stabilization, sample-loading robotics, and mail-in and remote data collection. These features allow users to gain valuable insights from both dynamic solution scattering and high-resolution atomic diffraction experiments performed at a single synchrotron beamline. Key practical issues considered for data collection and analysis include radiation damage, structural ensembles, alternative conformers and flexibility. SIBYLS develops and applies efficient combined MX and SAXS methods that deliver high-impact results by providing robust cost-effective routes to connect structures to biology and by performing experiments that aid beamline designs for next generation light sources. PMID:23396808

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

2013-01-17

321

Changes in macromolecular composition and morphology of Bacteroides fragilis cultured in a complex medium.  

PubMed Central

Changes in cell macromolecular composition during different phases of growth correlated with alterations in morphology of the obligately anaerobic bacterium, Bacteroides fragilis, grown in a complex medium. Images

Frantz, J C; McCallum, R E

1980-01-01

322

Spatial structure of transition metal complexes in solution determined by EXAFS spectroscopy  

NASA Astrophysics Data System (ADS)

CdK EXAFS, ZnK and CuK EXAFS and XANES spectra were measured for solutions of cadmium, zinc and copper dialkyldithiocarbamates in organic solvents with varying donating abilities: tributylphosphine, methylene chloride, benzene, dibutylsulfide, pyridine, dimethylsulfoxide and for some model compounds. The parameters of the local surroundings of the Cd, Zn and Cu atoms for complex forms in solutions were determined using EXAFS spectroscopy. Spatial structure models of the complex forms in a metal chelate - nonaqueous solvent system are suggested.

Erenburg, S. B.; Bausk, N. V.; Zemskova, S. M.; Mazalov, L. N.

2000-06-01

323

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

Microsoft Academic Search

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

David L. Masica; Jeffrey J. Gray

2009-01-01

324

Biophotonic probing of macromolecular transformations during apoptosis.  

PubMed

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

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

2010-07-06

325

Biophotonic probing of macromolecular transformations during apoptosis  

PubMed Central

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

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

2010-01-01

326

Macromolecular isoforms of Daphnia magna haemoglobin.  

PubMed

The haemoglobin (Hb) of Daphnia magna acclimated to different oxygen conditions was sampled, and in its natively assembled state it was separated by chromatofocusing. The Hb isoforms were analysed for their subunit composition under denaturating conditions by two-dimensional gel electrophoresis. The Hb system is suggested to consist of three predominant Hb aggregates, which are characterised by a specific subunit composition and synthesised in response to different ambient oxygen conditions. In normoxia, a dominant Hb aggregate (DmHbI) with a pI of 4.4-4.6 was composed of subunits B, C, E, F and G. In severe hypoxia, a different dominant Hb isoform (DmHbIII) with a pI of 5.7-5.9 was composed of subunits A, B, C, D, E and F. Further analyses in moderate hypoxia provided evidence for a third Hb isoform (DmHbII) composed of subunits B, C, D, E and F. Sequence alignment and homology modelling of the tertiary structure of the D. magna Hb domains 1 and 2 revealed functionally relevant substitutions of amino acid residues at positions B10, E7 and E11, which determine the functional properties of D. magna haemoglobin in terms of haem contact, oxygen binding and affinity. Both domains are predicted to possess the common haemoglobin fold, but helices C and D are not properly formed, and helix G is interrupted by a short coil. PMID:16307474

Lamkemeyer, Tobias; Paul, Rüdiger J; Stöcker, Walter; Yiallouros, Irene; Zeis, Bettina

2005-11-01

327

Structure stability of epitaxial MgO-CaO solid-solution films: effect of diffusion  

SciTech Connect

The nonequilibrium epitaxial growth process of Mg{sub x}Ca{sub 1-x}O solid-solution films at 600 degree sign C is carefully investigated. No obvious phase separation is observed until annealing at 800 degree sign C despite a large miscibility gap. The solid-solution film is featured with disorder alloy as confirmed by transmission electron microscopy (TEM). Spinodal decomposition caused by uprising diffusion happens after short-time annealing which explicitly indicates the structure stability of the metastable solid-solution films does result from diffusion quenching.

Li, H. D.; Zhang, X. N.; Zhang, Z.; Mei, Z. X.; Du, X. L.; Xue, Q. K. [Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Institute of Microstructure and Property of Advanced Materials, Beijing University of Technology, Beijing 100022 (China); Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China)

2007-05-15

328

Self-organization of amphiphilic macromolecules with local helix structure in concentrated solutions  

NASA Astrophysics Data System (ADS)

Concentrated solutions of amphiphilic macromolecules with local helical structure were studied by means of molecular dynamic simulations. It is shown that in poor solvent the macromolecules are assembled into wire-like aggregates having complex core-shell structure. The core consists of a hydrophobic backbone of the chains which intertwine around each other. It is protected by the shell of hydrophilic side groups. In racemic mixture of right-hand and left-hand helix macromolecules the wire-like complex is a chain of braid bundles of macromolecules with the same chirality stacking at their ends. The average number of macromolecules in the wire cross-section is close to that of separate bundles observed in dilute solutions of such macromolecules. The effects described here could serve as a simple model of self-organization in solutions of macromolecules with local helical structure.

Glagolev, M. K.; Vasilevskaya, V. V.; Khokhlov, A. R.

2012-08-01

329

Secondary structure and hydrogen bonding of crambin in solution. A two-dimensional NMR study.  

PubMed

The secondary structure of crambin in solution has been determined using two-dimensional NMR and is found to be essentially identical to that of the crystal structure. The H-D exchange of most amide protons can be accounted for in terms of the hydrogen bonds found in the X-ray structure. Exceptions are the amide protons of Cys-4 and Ser-6, which exchange more slowly than expected, and of Asn-46 for which the exchange is faster. These results might be explained by a slightly different conformation of the C-terminal region of the protein in solution. The slow exchange of the amides of Cys-32 and Glu-23 might be due to aggregation involving an extremely hydrophobic part of the protein in solution. PMID:3338468

Lamerichs, R M; Berliner, L J; Boelens, R; De Marco, A; Llinàs, M; Kaptein, R

1988-01-15

330

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

PubMed

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

Wu, Binbin; Diebold, Gerald J

2012-07-23

331

Distributions of structures and solute in directionally solidified Al - 7 wt % Si  

NASA Astrophysics Data System (ADS)

Bridgman experiments for various withdrawal rates were conducted in an Al - 7 wt % Si alloy. The dendrite arm spacing and the grain size of the primary dendritic aluminium-rich phase were measured, together with the spatial distribution of the interdendritic eutectic micro structure. A fine grain structure is observed for large pulling rates at constant temperature gradient, corresponding to a uniform distribution of the eutectic structure very close to the Gulliver-Scheil approximation. When decreasing the cooling rate, the average fraction of the eutectic structures decreases as it is expected based on back-diffusion. However, the distribution of the eutectic structure progressively looses uniformity and the grain size increases. Detailed analyses of these observations are conducted using a cellular automaton - finite element model. It allows the simulation of the local solidification path for an open system coupled with a solution of the heat and solute mass balances in the presence of fluid flow for the entire Bridgman sample. Evolutions of the size and density of structures are retrieved when increasing the cooling rates. This demonstrates the key role played by the thermosolutal buoyancy forces and their interaction with the solidifying dendritic grain structure to explain the distributions of structures and solute segregation.

Sabat Da Cruz, K.; Mangelinck-Noël, N.; Gandin, Ch-A.; Billia, B.

2012-01-01

332

Study on Macromolecular Rare Earth Complexes (IV)—Synthesis, Characterization and Fluorescent Properties of Rare Earth Complexes with Polymethyl Acrylic Acid  

Microsoft Academic Search

Polymethyl acrylic acid (PMAAc) with lower molecular weight was prepared by solution polymerization in water. A series of macromolecular rare earth complexes of PMAAc (RE?PMAAc, RE=La,Sm,Eu,Tb,Dy) have been synthesized and well characterized by means of elemental analysis, IR, TG?DTA analyses and fluorescence determination. Chemical analysis indicated that the molar ratio of –COO and RE in the complex was closely dependent

Guojian Duan; Ying Yang; Yuming Cui

2006-01-01

333

Numerical simulation of reflecting structures by solution of the two-dimensional Helmholtz equation  

SciTech Connect

A method is described for modeling two-dimensional reflecting structures based on a solution of the scalar Helmholtz equation. The equation is solved by use of an alternating-direction-implicit iterative method together with a semioptimum sequence of acceleration parameters similar to those introduced decades ago for the solution of elliptic equations with positive-definite operators. The resulting technique is efficient and simple to program, permits the simulation of complex structures with modest storage requirements, and is of very general applicability.

Hadley, G.R. (Sandia National Laboratories, Albuquerque, New Mexico 87185-5800 (United States))

1994-01-15

334

Nuclear magnetic resonance solution structure of dendrotoxin K from the venom of Dendroaspis polylepis polylepis.  

PubMed

The solution structure of dendrotoxin K (Toxin K), a protein consisting of one polypeptide chain with 57 residues purified from the venom of the black mamba, Dendroaspis polylepis polylepis, was determined by nuclear magnetic resonance (NMR) spectroscopy. On the basis of virtually complete sequence-specific 1H NMR assignments, including individual assignments for 38 pairs of diastereotopic substituents and side-chain amide protons, a total of 818 nuclear Overhauser effect distance constraints and 123 dihedral angle constraints were identified. Using this input, the solution structure of Toxin K was calculated with the program DIANA, and refined by restrained energy-minimization with a modified version of the program AMBER. The average root-mean-square deviation (r.m.s.d.) relative to the mean atomic co-ordinates of the 20 conformers selected to represent the solution structure is 0.31 A for all backbone atoms N, C alpha and C', and 0.90 A for all heavy-atoms of residues 2 to 56. The solution structure of Toxin K is very similar to the solution structure of the basic pancreatic trypsin inhibitor (BPTI) and the X-ray crystal structure of the alpha-dendrotoxin from Dendroaspis angusticeps (alpha-DTX), with r.m.s.d. values of 1.31 A and 0.92 A, respectively, for the backbone atoms of residues 2 to 56. Some local structural differences between Toxin K and BPTI are directly related to the fact that intermolecular interactions with two of the four internal molecules of hydration water in BPTI are replaced by intramolecular hydrogen bonds in Toxin K. PMID:8254670

Berndt, K D; Güntert, P; Wüthrich, K

1993-12-01

335

Effect of tumour cell-conditioned medium on endothelial macromolecular permeability and its correlation with collagen.  

PubMed Central

Conditioned medium prepared from mouse melanoma B16 cells (B16-CM) increases the macromolecular permeability of bovine aortic, venous and human umbilical vein endothelial monolayer. Collagen, which is synthesised by endothelial cells, has an important function in regulating the permeability of endothelial monolayer. Briefly, low collagen content leads to hyperpermeable structure of the endothelial monolayer. In the present studies, we examined the relationship between the increase of endothelial permeability and content of synthesised collagen of endothelial cells cultured with B16-CM. The B16-CM reduced endothelial collagen content but did not digest collagen directly. Matrix metalloproteinase inhibitor, 1,10-phenanthroline, inhibited the increase in permeability due to addition of B16-CM. These data suggest that B16-CM acts on endothelial cells, stimulating the digestion of endothelial collagen, and that the reduced content of collagen leads to the hyperpermeability of the endothelial monolayer.

Utoguchi, N.; Mizuguchi, H.; Dantakean, A.; Makimoto, H.; Wakai, Y.; Tsutsumi, Y.; Nakagawa, S.; Mayumi, T.

1996-01-01

336

Site-selective electroless nickel plating on patterned thin films of macromolecular metal complexes.  

PubMed

We demonstrate a simple route to depositing nickel layer patterns using photocross-linked polymer thin films containing palladium catalysts, which can be used as adhesive interlayers for fabrication of nickel patterns on glass and plastic substrates. Electroless nickel patterns can be obtained in three steps: (i) the pattern formation of partially quaterized poly(vinyl pyridine) by UV irradiation, (ii) the formation of macromolecular metal complex with palladium, and (iii) the nickel metallization using electroless plating bath. Metallization is site-selective and allows for a high resolution. And the resulting nickel layered structure shows good adhesion with glass and plastic substrates. The direct patterning of metallic layers onto insulating substrates indicates a great potential for fabricating micro/nano devices. PMID:21069972

Kimura, Mutsumi; Yamagiwa, Hiroki; Asakawa, Daisuke; Noguchi, Makoto; Kurashina, Tadashi; Fukawa, Tadashi; Shirai, Hirofusa

2010-11-11

337

The kinetic dose limit in room-temperature time-resolved macromolecular crystallography  

SciTech Connect

Protein X-ray structures are determined with ionizing radiation that damages the protein at high X-ray doses. As a result, diffraction patterns deteriorate with the increased absorbed dose. Several strategies such as sample freezing or scavenging of X-ray-generated free radicals are currently employed to minimize this damage. However, little is known about how the absorbed X-ray dose affects time-resolved Laue data collected at physiological temperatures where the protein is fully functional in the crystal, and how the kinetic analysis of such data depends on the absorbed dose. Here, direct evidence for the impact of radiation damage on the function of a protein is presented using time-resolved macromolecular crystallography. The effect of radiation damage on the kinetic analysis of time-resolved X-ray data is also explored.

Schmidt, M.; Srajer, V.; Purwar, N.; Tripathi, S. (UW); (UC)

2012-05-24

338

Improvements toward highly accurate diffraction experiments at the macromolecular micro-crystallography beamline BL-17A  

PubMed Central

BL-17A is a macromolecular crystallography beamline dedicated to diffraction experiments conducted using micro-crystals and structure determination studies using a lower energy X-ray beam. In these experiments, highly accurate diffraction intensity measurements are definitively important. Since this beamline was constructed, the beamline apparatus has been improved in several ways to enable the collection of accurate diffraction data. The stability of the beam intensities at the sample position was recently improved by modifying the monochromator. The diffractometer has also been improved. A new detector table was installed to prevent distortions in the diffractometer’s base during the repositioning of the diffractometer detector. A new pinhole system and an on-axis viewing system were installed to improve the X-ray beam profile at the sample position and the centering of tiny crystal samples.

Yamada, Yusuke; Chavas, Leonard M. G.; Igarashi, Noriyuki; Hiraki, Masahiko; Wakatsuki, Soichi; Matsugaki, Naohiro

2013-01-01

339

Solution structures of Alzheimer's amyloid A?13-23 peptide: NMR studies in solution and in SDS  

NASA Astrophysics Data System (ADS)

To be believed that interaction of amyloid peptides with the cellular membrane is one of the mechanisms for the neurotoxicity of A?. Therefore, structural studies of beta-amyloid in solution and in a "peptide-bio-membrane" complex are of intense interest. The aim of this study was to acquire a better understanding of the mechanism of "A? peptide-micelle surface" complex formation. Previous studies of A? peptides binding on the micelle surface show the presence of helical region between 15-24 residues and that fragment between 11-28 residues have a tendency to exit the hydrophobic environment of the micelle core and to bind to the micelle surface. In present paper we considered the fragment of A? from 13 to 23 residues and found that L17, F19 and F20 residues region play a great role in the process of binding of A? to the micelle surface.

Usachev, K. S.; Filippov, A. V.; Filippova, E. A.; Antzutkin, O. N.; Klochkov, V. V.

2013-10-01

340

Solvation of nitrophenol isomers: consequences for solute electronic structure and alkane/water partitioning.  

PubMed

Solute partitioning across a variety of alkane/aqueous interfaces was examined as a function of solute and alkane solvent structure. Solutes include p-nitrophenol (PNP), 3,5-dimethyl-p-nitrophenol (3,5-DMPNP), and 2,6-dimethyl-p-nitrophenol (2,6-DMPNP), the latter two being isomers distinguished solely by the location of methyl substituents on the aromatic ring. The alkane solvents included cylohexane, methylcyclohexane, octane, and iso-octane (2,2,4-trimethylpentane). PNP partitioned preferentially into the water by factors as high as 160:1. The dimethyl isomers partitioned more equally between water and the different alkanes. 2,6-DMPNP showed a 3-fold greater affinity for the alkane phase than 3,5-DMPNP. Ab initio calculations were used to characterize the molecular and electronic structure of the three solutes and to quantify individual contributions to each solute's solvation energy in model aqueous and alkane phases. Differences between 2,6-DMPNP and 3,5-DMPNP partitioning are interpreted based on the ability of the methyl groups in 2,6-DMPNP to weaken hydrogen bonding between the phenol group and adjacent water molecules. This diminished solvation interaction reduces the barrier to solute migration into the nonpolar organic phase despite the fact that 2,6-DMPNP has a larger (calculated) permanent, ground-state dipole than 3,5-DMPNP. PMID:19143574

Steel, William H; Foresman, James B; Burden, Daniel K; Lau, Yuen Y; Walker, Robert A

2009-01-22

341

The Solution Structure of a Chimeric LEKTI Domain Reveals a Chameleon Sequence †  

Microsoft Academic Search

The conversion of an R-helical to a ‚-strand conformation and the presence of chameleon sequences are fascinating from the perspective that such structural features are implicated in the induction of amyloid-related fatal diseases. In this study, we have determined the solution structure of a chimeric domain (Dom1PI) from the multidomain Kazal-type serine proteinase inhibitor LEKTI using multi- dimensional NMR spectroscopy.

Henning Tidow; Thomas Lauber; Klaus Vitzithum; Christian P. Sommerhoff; Paul Rösch; Ute C. Marx

2004-01-01

342

Surface Atomic Structure of KDP Crystals in Aqueous Solution: An Explanation of the Growth Shape  

Microsoft Academic Search

With this study on KDP, we present an interface atomic structure determination of a crystal in contact with its growth solution. Using x-ray diffraction at a third-generation synchrotron radiation source, the structure of both the \\\\{101\\\\} and \\\\{100\\\\} faces has been determined. We found that the \\\\{101\\\\} faces are terminated by a layer of K+ ions and not by H2PO

S. A. de Vries; P. Goedtkindt; S. L. Bennett; W. J. Huisman; M. J. Zwanenburg; D.-M. Smilgies; J. J. de Yoreo; W. J. P. van Enckevort; P. Bennema; E. Vlieg

1998-01-01

343

Solution structure of the cellular factor BAF responsible for protecting retroviral DNA from autointegration  

Microsoft Academic Search

The solution structure of the human barrier-to-autointegration factor, BAF, a 21,000 Mr dimer, has been solved by NMR, including extensive use of dipolar couplings which provide a priori long range structural information. BAF is a highly evolutionarily conserved DNA binding protein that is responsible for inhibiting autointegration of retroviral DNA, thereby promoting integration of retroviral DNA into the host chromosome.

Mengli Cai; Ying Huang; Ronglan Zheng; Shui-Qing Wei; Rodolfo Ghirlando; Myung Soo Lee; Robert Craigie; Angela M. Gronenborn; G. Marius Clore

1998-01-01

344

Layer structured graphite oxide as a novel adsorbent for humic acid removal from aqueous solution  

Microsoft Academic Search

Layer structured graphite oxide (GO) was prepared from graphite using the Hummers–Offeman method, characterised using N2 adsorption, XRD, XPS, SEM(TEM), and FT-IR, and tested for humic acid (HA) adsorption in aqueous solution. XRD, XPS, and FT-IR measurements indicate the formation of layered structure with strong functional groups of GO. It is also found that the GO exhibits strong and much

Tri Hartono; Shaobin Wang; Qing Ma; Zhonghua Zhu

2009-01-01

345

Three-dimensional structure of soybean trypsin\\/chymotrypsin Bowman-Birk inhibitor in solution  

Microsoft Academic Search

The three-dimensional structure of soybean trypsin\\/chymotrypsin Bowman-Birk inhibitor in solution has been determined by two-dimensional ¹H nuclear magnetic resonance spectroscopy and dynamical simulated annealing using the program XPLOR. The structure was defined by 907 NOEs involving intra- and interresidue contacts which served as distance constraints for a protocol of dynamical simulated annealing. In addition, 48 Ï angle constraints involving non-proline

Milton H. Werner; David E. Wemmer

1992-01-01

346

Solution structure of an informationally complex high-affinity RNA aptamer to GTP  

Microsoft Academic Search

Higher-affinity RNA aptamers to GTP are more informationally complex than lower-affinity aptamers. Analog binding studies have shown thatthe additional informationneeded toimproveaffinity doesnot specify moreinteractions withthe ligand. Inlightof those observations, we would like to understand the structural characteristics that enable complex aptamers to bind their ligands with higher affinity. Here we present the solution structure of the 41-nt Class I GTP

JAMES M. CAROTHERS; JONATHAN H. DAVIS; JAMES J. CHOU; JACK W. SZOSTAK

2006-01-01

347

Structural character of ?-syn12 peptide in solution at high pH  

Microsoft Academic Search

The dynamics and structural character of a-syn12 peptide in aqueous solution at high pH has been investigated through temperature replica exchange molecular dynamics simulations by using GROMOS 43A1 force field. The isolated a-syn12 peptide adopts in water an a-helix structure at high pH. These results are distinct from other amyloid disease protein at neutral pH.

Lixia Liu

2010-01-01

348

A QMCF-MD investigation of the structure and dynamics of Ce4+ in aqueous solution.  

PubMed

A quantum-mechanical charge-field molecular dynamics simulation has been performed for a tetravalent Ce ion in aqueous solution. In this framework, the complete first and second hydration spheres are treated by ab initio quantum mechanics supplemented by an electrostatic embedding technique, making the construction of non-Coulombic solute-solvent potentials unnecessary. During the 10 ps of simulation time, the structural aspects of the solution were analyzed by various methods. Experimental results such as the mean Ce-O bond distance and the predicted first-shell coordination number were compared to the results obtained from the simulation resolving some ambiguities in the literature. The dynamics of the system were characterized by mean ligand residence times and frequency/force constant calculations. Furthermore, Ce-O and Ce-H angular radial distribution plots were employed, yielding deeper insight into the structural and dynamical aspects of the system. PMID:22651096

Lutz, Oliver M D; Hofer, Thomas S; Randolf, Bernhard R; Weiss, Alexander K H; Rode, Bernd M

2012-05-31

349

The Baryonic Branch of Klebanov-Strassler Solution: a Supersymmetric Family of SU(3) Structure Backgrounds  

NASA Astrophysics Data System (ADS)

We exhibit a one-parameter family of regular supersymmetric solutions of type IIB theory that describes the baryonic branch of the Klebanov-Strassler (KS) theory. The solution is obtained by applying the supersymmetry conditions for SU(3)-structure manifolds to an interpolating ansatz proposed by Papadopoulos and Tseytlin. Other than at the KS point, the family does not have a conformally-Ricci-flat metric, neither it has self-dual three-form flux. By varying also the string coupling, our solution smoothly interpolates between Klebanov-Strassler and Maldacena-Nuñez (MN). The asymptotic IR and UV are that of KS throughout the interpolating flow, except for the extremal value of the parameter where the UV solution drastically changes to MN.

Butti, Agostino; Graña, Mariana; Minasian, Ruben; Petrini, Michela; Zaffaroni, Alberto

2005-03-01

350

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

SciTech Connect

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

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

2007-10-01

351

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

SciTech Connect

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

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

2008-01-01

352

Atomistic simulation of local structure and mixing properties of mineral solid solutions  

Microsoft Academic Search

At present there are several ways to simulate solid solution structure and properties by using ab initio as well as semi-empirical (atomistic) approaches [1]. The main problem of each approach is a reasonable representation of random distribution of atoms substituting each other over common positions. A procedure in operation here used large supercells and generation of most disordered atomic configurations

V. S. Urusov

2009-01-01

353

Coagulation-diffusion systems: Derivation and existence of solutions for the diffuse interface structure equations  

Microsoft Academic Search

This paper considers an infinite system of partial differential equations, the coagulation-diffusion equations, which add spatial diffusion to the classical coagulation equations. The main emphasis is placed on deriving an infinite system of ordinary differential equations which described the structured interface between reacting coagulation and dilute concentration. Existence of solutions to interfacial equaitons is proven under spatial boundary conditions. Sponsored

M. Slemrod

1990-01-01

354

Structural competition between halogen bonds and lone-pair···? interactions in solution.  

PubMed

Structural competition between halogen bonds and lone-pair···? interactions in solution is studied using (13)C NMR combined with density functional theory calculations. Among the halogen bonds considered, only the iodine bonds and a few bromine bonds are strong enough to compete successfully with the lone-pair···? interactions. PMID:22378691

Ma, Ning; Zhang, Yu; Ji, Baoming; Tian, Anmin; Wang, Weizhou

2012-02-29

355

The role of structural and semantic factors in the solution of algebra speed problems  

Microsoft Academic Search

A model for the solution of speed problems was proposed which is based on their structure, and its component schemata of INFER DURATION RELATION and INFER LENGTH underlie the representation and modelling of these problems. The acquisition of the INFER RELATION schemata and their use were studied by testing 178 ninth to eleventh grade students. Tests included three isomorphic problems

Ron Hoz; Guershon Harel; Jack Tedeski

1997-01-01

356

An Explicit Solution of the Power Balance Equations of Structure Preserving Power System Models  

Microsoft Academic Search

In this paper, we consider the widely popular structure-preserving models used to describe the dynamic behavior of multimachine power systems. These models consist of differential-algebraic equations, where the algebraic constraints stem from the power flow balance between generators, loads, and lines. Our main contribution is the explicit computation of a solution for these algebraic equations under the assumption that the

Wissam Dib; Andrey E. Barabanov; Romeo Ortega; FranÇoise Lamnabhi-Lagarrigue

2009-01-01

357

The Structure and Decomposition of Titanium and Zirconium B.C.C. Solid Solutions.  

National Technical Information Service (NTIS)

The research was concerned with studying the structure, the mechanical properties and the decomposition of Ti and Zr b.c.c. (e.g. Zr-Nb, Ti-V) solid solutions. The experimental techniques used in this study were electron microscopy, electron diffraction, ...

S. L. Sass

1974-01-01

358

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

Microsoft Academic Search

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

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

2004-01-01

359

Structure of steady state accretion shocks with several cooling functions: Closed integral-form solution  

Microsoft Academic Search

We present, for the first time, a closed integral-form solution to the accretion shock structures for the case where the cooling is due to optically thin bremsstrahlung emission and a series of power-law cooling functions of density and temperature. Our results can provide useful checks on numerical calculations and simple accurate estimates for valuable parameters such as the shock height.

Kinwah Wu; G. Chanmugam; G. Shaviv

1994-01-01

360

Exchange rate anomalies in the industrial countries: A solution with a structural VAR approach  

Microsoft Academic Search

Past empirical research on the effects of monetary policy in closed and open economies found evidence of several anomalies, such as the ‘liquidity’, ‘price’, ‘exchange rate’ and ‘forward discount bias’ puzzles. In this paper, we develop an approach that provides a solution to these empirical anomalies in an open economy setup. We use a ‘structural VAR’ approach with non-recursive contemporaneous

Soyoung Kim; Nouriel Roubini

2000-01-01

361

Reducing radiation damage in macromolecular crystals at synchrotron sources.  

PubMed

A new strategy is presented to reduce primary X-ray damage in macromolecular crystallography. The strategy is based on separating the diffracting and damaged regions as much as feasible. The source of the radiation damage to macromolecular crystals is from two primary mechanisms: the direct excitations of electrons by absorption, and inelastic scattering of the X-rays. The first produces photoelectrons with their accompanying Auger electrons from relaxation of the core hole and the second creates Compton electrons. The properties of these two mechanisms and calculations of primary X-ray damage quantify how to modify the spatial distribution of X-rays to reduce the deleterious effects of radiation damage. By focusing the incident X-rays into vertical stripes, it is estimated that the survival (the time during which quality diffraction data can be obtained with a given X-ray flux) of large crystals can be increased by at least a factor of 1.6, while for very small platelet crystals the survival can be increased by up to a factor of 14. PMID:19307718

Stern, Edward A; Yacoby, Yizhak; Seidler, Gerald T; Nagle, Kenneth P; Prange, Micah P; Sorini, Adam P; Rehr, John J; Joachimiak, Andrzej

2009-03-19

362

Preparation of macromolecular complexes for cryo-electron microscopy  

PubMed Central

This protocol describes the preparation of frozen-hydrated single-particle specimens of macromolecular complexes. First, it describes how to create a grid surface coated with holey carbon by first inducing holes in a Formvar film to act as a template for the holey carbon that is stable under cryo-electron microscopy (cryo-EM) conditions and is sample-friendly. The protocol then describes the steps required to deposit the homogeneous sample on the grid and to plunge-freeze the grid into liquid ethane at the temperature of liquid nitrogen, so that it is suitable for cryo-EM visualization. It takes 4–5 h to make several hundred holey carbon grids and about 1 h to make the frozen-hydrated grids. The time required for sample purification varies from hours to days, depending on the sample and the specific procedure required. A companion protocol details how to collect cryo-EM data using an FEI Tecnai transmission electron microscope that can subsequently be processed to obtain a three-dimensional reconstruction of the macromolecular complex.

Grassucci, Robert A; Taylor, Derek J; Frank, Joachim

2009-01-01

363

Thiomers for oral delivery of hydrophilic macromolecular drugs.  

PubMed

In recent years thiolated polymers (thiomers) have appeared as a promising new tool in oral drug delivery. Thiomers are obtained by the immobilisation of thio-bearing ligands to mucoadhesive polymeric excipients. By the formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of thiomers are up to 130-fold improved compared with the corresponding unmodified polymers. Owing to the formation of inter- and intramolecular disulfide bonds within the thiomer itself, matrix tablets and particulate delivery systems show strong cohesive properties, resulting in comparatively higher stability, prolonged disintegration times and a more controlled drug release. The permeation of hydrophilic macromolecular drugs through the gastrointestinal (GI) mucosa can be improved by the use of thiomers. Furthermore, some thiomers exhibit improved inhibitory properties towards GI peptidases. The efficacy of thiomers in oral drug delivery has been demonstrated by various in vivo studies. A pharmacological efficacy of 1%, for example, was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Furthermore, tablets comprising a thiomer and pegylated insulin resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Low-molecular-weight heparin embedded in thiolated polycarbophil led to an absolute bioavailability of > or = 20% after oral administration to rats. In these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. These results indicate drug carrier systems based on thiomers appear to be a promising tool for oral delivery of hydrophilic macromolecular drugs. PMID:16296722

Bernkop-Schnürch, Andreas; Hoffer, Martin H; Kafedjiiski, Krum

2004-11-01

364

Variable effects of soman on macromolecular secretion by ferret trachea  

SciTech Connect

The purpose of this study was to examine the effect of the anticholinesterase agent, soman, on macromolecular secretion by ferret trachea, in vitro. We mounted pieces of ferret trachea in Ussing-type chambers. Secreted sulfated macromolecules were radiolabeled by adding 500 microCi of {sup 35}SO{sub 4} to the submucosal medium and incubating for 17 hr. Soman added to the submucosal side produced a concentration-dependent increase in radiolabeled macromolecular release with a maximal secretory response (mean +/- SD) of 202 +/- 125% (n = 8) relative to the basal secretion rate at a concentration of 10{sup {minus} 7} M. The addition of either 10{sup {minus}6} M pralidoxime (acetylcholinesterase reactivator) or 10{sup {minus}6} M atropine blocked the response to 10{sup {minus}7} M soman. At soman concentrations greater than 10{sup {minus}7} M, secretion rate decreased and was not significantly different from basal secretion. Additional experiments utilizing acetylcholine and the acetylcholinesterase inhibitor, physostigmine, suggest that inhibition of secretion by high concentrations of soman may be due to a secondary antagonistic effect of soman on muscarinic receptors.

McBride, R.K.; Zwierzynski, D.J.; Stone, K.K.; Culp, D.J.; Marin, M.G. (Univ. of Rochester School of Medicine and Dentistry, NY (USA))

1991-01-01

365

Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior  

PubMed Central

Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs) via immunocytochemistry, atomic force microscopy (AFM), and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro.

Zeiger, Adam S.; Loe, Felicia C.; Li, Ran; Raghunath, Michael; Van Vliet, Krystyn J.

2012-01-01

366

Spacetime structure of static solutions in Gauss-Bonnet gravity: Neutral case  

NASA Astrophysics Data System (ADS)

We study the spacetime structures of the static solutions in the n-dimensional Einstein-Gauss-Bonnet-? system systematically. We assume the Gauss-Bonnet coefficient ? is non-negative and a cosmological constant is either positive, zero, or negative. The solutions have the (n-2)-dimensional Euclidean submanifold, which is the Einstein manifold with the curvature k=1, 0, and -1. We also assume 4?˜/?2?1, where ? is the curvature radius, in order for the sourceless solution (M=0) to be defined. The general solutions are classified into plus and minus branches. The structures of the center, horizons, infinity, and the singular point depend on the parameters ?, ?2, k, M, and branches complicatedly so that a variety of global structures for the solutions are found. In our analysis, the M˜-r diagram is used, which makes our consideration clear and enables easy understanding by visual effects. In the plus branch, all the solutions have the same asymptotic structure at infinity as that in general relativity with a negative cosmological constant. For the negative-mass parameter, a new type of singularity called the branch singularity appears at nonzero finite radius r=rb>0. The divergent behavior around the singularity in Gauss-Bonnet gravity is milder than that around the central singularity in general relativity. There are three types of horizons: inner, black hole, and cosmological. In the k=1,0 cases, the plus-branch solutions do not have any horizon. In the k=-1 case, the radius of the horizon is restricted as rh?(2?˜)) in the plus (minus) branch. The black hole solution with zero or negative mass exists in the plus branch even for the zero or positive cosmological constant. There is also the extreme black hole solution with positive mass. We briefly discuss the effect of the Gauss-Bonnet corrections on black hole formation in a collider and the possibility of the violation of the third law of the black hole thermodynamics.

Torii, Takashi; Maeda, Hideki

2005-06-01

367

The Rheo-Optics of Shear-Thickening and Structure Formation in Polymer Solutions  

NASA Astrophysics Data System (ADS)

Simultaneous measurements of the optical and rheological response of solutions of polystyrene have been made, in -situ, in order to ascertain the connection between structure formation and the phenomenon of shear-thickening. Transient and steady state measurements of the viscosity, dichroism, birefringence and associated orientation angles were carried out in decalin and bromobenzene in the semi-dilute region using a couette device capable of shear rates up to 8,000 s^{-1}.. Light scattering calculations using the Anomalous Diffraction Approximation (ADA) for large particles, the Rayleigh approximation for isotropic, uniaxial spheroids and the flexible macromolecule model, provide a phenomenologically consistent explanation for the observed behavior. A one -to-one correlation was found between the occurrence of maxima in dichroism and minima in viscosity which demonstrates that shear-thickening is caused by structure formation in solution. Kinetics of the formation of the structures in solution are instantaneous and completely reversible. For solutions that exhibited shear-thinning no maximum in dichroism was seen, the dichroism instead saturated at high shear rates. Calculations using the ADA suggest that shear -thickening and the associated dichroism behavior result from the flow-induced production and growth of spheroidal, micron-size particles in solution. These particles are isotropic (i.e. liquid-like) and align in the flow direction. In the case of shear-thinning solutions, the Rayleigh approximation for sub-micron, isotropic spheroids was successfully used to account for the magnitude of the saturating dichroism behavior, suggesting that groups of entangled polymer chains may be forming in the solutions which give rise to the optical behavior. Thus, the size of the particles that form in solution upon imposition of flow determines whether shear-thickening will occur. For particles which remain sub-micron over the entire shear rate range, the solution exhibits shear -thinning. If the particles continue to grow, eventually becoming a few microns in size, the solution exhibits shear -thickening. On the other hand, the birefringence was found to be dominated by the chains or entanglements still present in the dissolved state. This behavior could be modeled on the basis of the elastic dumbell theory, suitably modified to include both macroform and microform optical anisotropies.

Kishbaugh, Alan Jay

1992-01-01

368

Recent Major Improvements to the ALS Sector 5 MacromolecularCrystallography Beamlines  

SciTech Connect

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

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

2007-07-01

369

Solution Structure of a DNA Quadruplex Containing the Fragile X Syndrome Triplet Repeat  

Microsoft Academic Search

Both X-ray and NMR structural studies have defined the polymorphic nature of G-quadruplexes generated through mutual stacking of G·G·G·G tetrads by guanine rich telomeric sequences. Recently, the fragile X syn- drome d(C-G-G)ntriplet nucleotide repeat has been shown to form a stable quadruplex of undefined structure in monovalent cation solution. We have undertaken a structural characterization of the d(G-C-G-G-T3-G-C-G-G) undecanucleotide to

Abdelali Kettani; Ajay R. Kumar; Dinshaw J. Patel

1995-01-01

370

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

NASA Astrophysics Data System (ADS)

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

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

1998-06-01

371

Solvent stabilized solution structures of galanin and galanin analogs, studied by circular dichroism spectroscopy.  

PubMed

Circular dichroism spectroscopy has been used to study how different solvents stabilize secondary structure in the neuropeptide galanin (rat), two N-terminal fragments of galanin, galanin(1-12) and galanin(1-16), and six other differently charged analogs. Among these analogs, the peptide M40, galanin(1-13)-Pro-Pro-Ala-Leu-Ala-Leu-Ala amide, is a high affinity, receptor subtype specific galanin receptor antagonist. The different solvents include sodium dodecyl sulfate (SDS) micelle solutions, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phosphoglycerol (DOPG) vesicle solutions. 100% 1,1,1,3,3,3-hexafluoro-2-propanol (HFP) and 100% 2,2,2-trifluoroethanol (TFE). DOPC vesicles did not change the structure of the peptides as compared to aqueous solvent. The negatively charged DOPG vesicles and SDS micelles induced similar changes towards alpha-helical structures in all peptides. The HFP and TFE solvents have an even stronger tendency to stabilize alpha-helical conformations in these peptides. Since DOPG vesicles can be considered as a model system for negatively charged biological membranes, the solution structures observed in the presence of DOPG or SDS may be the most relevant for the in vivo situation. Correlations between the binding affinity of the peptides to hippocampal galanin receptors and their observed structures in the DOPG solvent were investigated. PMID:7540871

Ohman, A; Lycksell, P O; Andell, S; Langel, U; Bartfai, T; Gräslund, A

1995-06-14

372

X-ray absorption spectroscopic investigation of the electronic structure differences in solution and crystalline oxyhemoglobin.  

PubMed

Hemoglobin (Hb) is the heme-containing O2 transport protein essential for life in all vertebrates. The resting high-spin (S = 2) ferrous form, deoxy-Hb, combines with triplet O2, forming diamagnetic (S = 0) oxy-Hb. Understanding this electronic structure is the key first step in understanding transition metal-O2 interaction. However, despite intense spectroscopic and theoretical studies, the electronic structure description of oxy-Hb remains elusive, with at least three different descriptions proposed by Pauling, Weiss, and McClure-Goddard, based on theory, spectroscopy, and crystallography. Here, a combination of X-ray absorption spectroscopy and extended X-ray absorption fine structure, supported by density functional theory calculations, help resolve this debate. X-ray absorption spectroscopy data on solution and crystalline oxy-Hb indicate both geometric and electronic structure differences suggesting that two of the previous descriptions are correct for the Fe-O2 center in oxy-Hb. These results support the multiconfigurational nature of the ground state developed by theoretical results. Additionally, it is shown here that small differences in hydrogen bonding and solvation effects can tune the ground state, tipping it into one of the two probable configurations. These data underscore the importance of solution spectroscopy and show that the electronic structure in the crystalline form may not always reflect the true ground-state description in solution. PMID:24062465

Wilson, Samuel A; Green, Evan; Mathews, Irimpan I; Benfatto, Maurizio; Hodgson, Keith O; Hedman, Britt; Sarangi, Ritimukta

2013-09-23

373

Extended D'Alembert solution of finite length second order flexible structures with damped boundaries  

NASA Astrophysics Data System (ADS)

The paper considers the problem of deriving the exact response to initial conditions of flexible structures governed by the wave equation with boundary conditions of pure damping. The aim is to develop a wave oriented solution for this non-conservative case that is hardly considered in classical vibration theory. The celebrated D'Alembert approach, which applies to systems of infinite length, is extended to systems with finite medium and non-conservative boundary conditions. Displacement and velocity responses of the structure are developed in terms of propagating waves with decreasing amplitude. It is shown that additional waves exist as a result of non-zero initial displacement at the ends. An equivalent infinite structure and its corresponding initial conditions are then defined so that the solution is given in a D'Alembert like fashion, using single progressive and regressive waves.

Sirota, Lea; Halevi, Yoram

2013-08-01

374

A new NMR solution structure of the SL1 HIV-1Lai loop-loop dimer  

PubMed Central

Dimerization of genomic RNA is directly related with the event of encapsidation and maturation of the virion. The initiating sequence of the dimerization is a short autocomplementary region in the hairpin loop SL1. We describe here a new solution structure of the RNA dimerization initiation site (DIS) of HIV-1Lai. NMR pulsed field-gradient spin-echo techniques and multidimensional heteronuclear NMR spectroscopy indicate that this structure is formed by two hairpins linked by six Watson–Crick GC base pairs. Hinges between the stems and the loops are stabilized by intra and intermolecular interactions involving the A8, A9 and A16 adenines. The coaxial alignment of the three A-type helices present in the structure is supported by previous crystallography analysis but the A8 and A9 adenines are found in a bulged in position. These data suggest the existence of an equilibrium between bulged in and bulged out conformations in solution.

Kieken, Fabien; Paquet, Francoise; Brule, Fabienne; Paoletti, Jacques; Lancelot, Gerard

2006-01-01

375

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

SciTech Connect

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

Taylor, Seth T.

2002-05-17

376

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

NASA Astrophysics Data System (ADS)

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

Boddohi, Soheil; Killingsworth, Christopher; Kipper, Matt

2008-03-01

377

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

PubMed

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

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

2012-11-22

378

[Optimization of the methods for small peptide solution structure determination by NMR spectroscopy].  

PubMed

NMR spectroscopy was recognized as a method of protein structure determination in solution. However, determination of the conformation of small peptides, which undergo fast molecular motions, remains a challenge. This is mainly caused by impossibility to collect required quantity of the distance and dihedral angle restraints from NMR spectra. At the same time, short charged peptides play an important role in a number of biological processes, in particular in pathogenesis of neurodegenerative diseases including Alzheimer's disease. Therefore development of a method for structure calculation of small peptides in a water environment using the most realistic force fields seems to be of current importance. Such algorithm has been developed using the Amber-03 force field and software package Gromacs after updating its program code. The algorithm of calculation has been verified on a model peptide for which the solution structure is known, and on the metal binding fragment of rat beta-amyloid for which structure has been determined by alternative methods. The developed algorithm substantially increases quality of structures, in particular Ramachandran plot statistics, and decreases RMSD of coordinates of atoms inside calculated family. The described protocol of calculation can be used for determination of conformation of short peptides, and also for structure optimization of larger proteins containing poorly structured fragments. PMID:21290829

Istrate, A N; Mantsyzov, A B; Kozin, S A; Pol'shakov, V I

379

A hybrid computational-experimental approach for automated crystal structure solution.  

PubMed

Crystal structure solution from diffraction experiments is one of the most fundamental tasks in materials science, chemistry, physics and geology. Unfortunately, numerous factors render this process labour intensive and error prone. Experimental conditions, such as high pressure or structural metastability, often complicate characterization. Furthermore, many materials of great modern interest, such as batteries and hydrogen storage media, contain light elements such as Li and H that only weakly scatter X-rays. Finally, structural refinements generally require significant human input and intuition, as they rely on good initial guesses for the target structure. To address these many challenges, we demonstrate a new hybrid approach, first-principles-assisted structure solution (FPASS), which combines experimental diffraction data, statistical symmetry information and first-principles-based algorithmic optimization to automatically solve crystal structures. We demonstrate the broad utility of FPASS to clarify four important crystal structure debates: the hydrogen storage candidates MgNH and NH(3)BH(3); Li(2)O(2), relevant to Li-air batteries; and high-pressure silane, SiH(4). PMID:23178265

Meredig, Bryce; Wolverton, C

2012-11-25

380

Structure and intermolecular interactions in selected binary solutions studied by X-ray methods  

NASA Astrophysics Data System (ADS)

The results of X-ray structural studies of liquid chloroanisole C6H4OCH3Cl and 10% solutions of chloroanisole in 1,4-dimethylbenzene C8H10 are presented. It is the first paper on an X-ray diffraction study of the liquid solutions of chloroanisole. The X-ray measurements were made at 293 K for the scattering angle range 2? varying from 6° to 120°. Averaged scattered X-ray angular distributions I¯(S) were determined. The angular distributions of the intensity of X-ray scattered by 10% solutions of chloroanisole in 1,4-dimethylbenzene were compared to the angular distributions obtained for liquid ortho-, meta- and para-chloroanisole. The differential radial distribution functions of electron density 4?r?j,knK[?k(r)??0] were numerically found using the Fourier analysis from a modified Warren, Krutter and Morningstar equation. To the maxima of DRDFs, interatomic and intermolecular distances were assigned. The use of short-wave radiation from an X-ray tube with a molybdenum anode permitted determination of the spheres of intermolecular ordering in the studied liquids and their solutions. The experimental results were used to plot models of the most highly probable mutual disposition of the molecules in liquid chloroanisole and their solutions. The benzene rings of two molecules are situated in parallel plane what results in antiparallel setting of the dipole moments of the chloroanisole molecules. X-ray structural analysis was applied to determine the packing coefficients of chloroanisole molecules. The results obtained in this paper confirm the specific structural properties of the solutions studied.

Drozdowski, Henryk; Romaniuk, Anna; B?aszczak, Zdzis?aw

2013-12-01

381

NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region  

Microsoft Academic Search

BCL2 protein functions as an inhibitor of cell apoptosis and has been found to be aberrantly expressed in a wide range of human diseases. A highly GC-rich region upstream of the P1 promoter plays an important role in the transcriptional regu- lation of BCL2. Here we report the NMR solution structure of the major intramolecular G-quadruplex formed on the G-rich

Jixun Dai; Ding Chen; Roger A. Jones; Laurence H. Hurley; Danzhou Yang

2006-01-01

382

Analytical solutions of the Poisson-Boltzmann equation: biological applications  

NASA Astrophysics Data System (ADS)

Electrostatic interactions are a key factor for determining many properties of bio-molecules. The ability to compute the electrostatic potential generated by a molecule is often essential in understanding the mechanism behind its biological function such as catalytic activity, ligand binding, and macromolecular association. We propose an approximate analytical solution to the (linearized) Poisson-Boltzmann (PB) equation that is suitable for computing electrostatic potential around realistic biomolecules. The approximation is tested against the numerical solutions of the PB equation on a test set of 600 representative structures including proteins, DNA, and macromolecular complexes. The approach allows one to generate, with the power of a desktop PC, electrostatic potential maps of virtually any molecule of interest, from single proteins to large protein complexes such as viral capsids. The new approach is orders of magnitude less computationally intense than its numerical counterpart, yet is almost equal in accuracy. When studying very large molecular systems, our method is a practical and inexpensive way of computing bio- molecular potential at atomic resolution. We demonstrate the usefullnes of the new approach by exploring the details of electrostatic potentials generated by two of such systems: the nucleosome core particle (25,000 atoms) and tobacco ring spot virus (500,000 atoms). Biologically relevant insights are generated.

Fenley, Andrew; Gordon, John; Onufriev, Alexey

2006-03-01

383

The global structure of periodic solutions to a suspension bridge mechanical model  

NASA Astrophysics Data System (ADS)

We study two systems of nonlinearly coupled ordinary differential equations that govern the vertical and torsional motions of a cross-section of a suspension bridge. We observe numerically that the structure of the set of periodic solutions changes considerably when we smooth the nonlinear terms. The smoothed nonlinearities describe the force that we wish to model more realistically and the resulting periodic solutions more accurately replicate the phenomena observed at the Tacoma Narrows Bridge on the day of its collapse. The main conclusion is that purely vertical periodic forcing can result in subharmonic primarily torsional motion.

McKenna, P. J.; Moore, K. S.

2002-10-01

384

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

SciTech Connect

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

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

2006-09-01

385

Solution structure of a beta-peptide ligand for hDM2.  

PubMed

We recently reported a beta-peptide foldamer, beta53-1, that folds into a 14-helix in aqueous solution, binds the oncoprotein hDM2 with submicromolar affinity, and potently inhibits the interaction of hDM2 with a peptide derived from the activation domain of p53 (p53AD). Here, we present the solution structure of beta53-1 in methanol. Details of the structure illustrate fundamental and novel elements of beta-peptide folding and recognition. These elements include the detailed arrangement of a complex, 14-helix-stabilizing salt bridge on one helical face, and a unique "wedge into cleft" packing interaction along a second. The structure also reveals how a subtle distortion in the beta53-1 14-helix geometry alters the presentation of its recognition epitope, rendering it particularly well suited for alpha-helix mimicry. The solution structure of beta53-1 demonstrates that well folded beta-peptide oligomers can effectively present an extended, highly variable surface that could be used as a general platform for targeting critical protein-protein interfaces. PMID:15783163

Kritzer, Joshua A; Hodsdon, Michael E; Schepartz, Alanna

2005-03-30

386

Solution structure and dynamics of human ubiquitin conjugating enzyme Ube2g2  

PubMed Central

Ube2g2 is an E2 enzyme which functions as part of the endoplasmic reticulum-associated degradation (ERAD) pathway responsible for identification and degradation of misfolded proteins in the endoplasmic reticulum. In tandem with a cognate E3 ligase, Ube2g2 assembles K48-linked polyubiquitin chains and then transfers them to substrate, leading ultimately to proteasomal degradation of the polyubiquitin-tagged substrate. We report here the solution structure and backbone dynamics of Ube2g2 solved by nuclear magnetic resonance spectroscopy. Although the solution structure agrees well with crystallographic structures for the E2 core, catalytically important loops (encompassing residues 95-107 and 130-135) flanking the active site cysteine are poorly defined. 15N spin relaxation and residual dipolar coupling analysis directly demonstrates that these two loops are highly dynamic in solution. These results suggest that Ube2g2 requires one or more of its protein partners, such as cognate E3, acceptor ubiquitin substrate or thiolester-linked donor ubiquitin, in order to assume its catalytically relevant conformation. Within the NMR structural ensemble, interactions were observed between His94 and the highly mobile loop residues Asp98 and Asp99, supporting a possible role for His94 as a general base activated by the carboxylate side-chains of Asp98 or Asp99.

Ju, Tingting; Bocik, William; Majumdar, Ananya; Tolman, Joel R.

2009-01-01

387

Polydimethylsiloxane as a macromolecular additive for enhanced performance of molecular bulk heterojunction organic solar cells.  

PubMed

The effect of the macromolecular additive, polydimethylsiloxane (PDMS), on the performance of solution processed molecular bulk heterojunction solar cells is investigated, and the addition of PDMS is shown to improve device power conversion efficiency by ?70% and significantly reduce cell-to-cell variation, from a power conversion efficiency of 1.25 ± 0.37% with no PDMS to 2.16 ± 0.09% upon the addition of 0.1 mg/mL PDMS to the casting solution. The cells are based on a thiophene and isoindigo containing oligomer as the electron donor and [6,6]-phenyl-C61 butyric acid methyl ester (PC(61)BM) as the electron acceptor. PDMS is shown to have a strong influence on film morphology, with a significant decrease in film roughness and feature size observed. The morphology change leads to improved performance parameters, most notably an increase in the short circuit current density from 4.3 to 6.8 mA/cm(2) upon addition of 0.1 mg/mL PDMS. The use of PDMS is of particular interest, as this additive appears frequently as a lubricant in plastic syringes commonly used in device fabrication; therefore, PDMS may unintentionally be incorporated into device active layers. PMID:21405105

Graham, Kenneth R; Mei, Jianguo; Stalder, Romain; Shim, Jae Won; Cheun, Hyeunseok; Steffy, Fred; So, Franky; Kippelen, Bernard; Reynolds, John R

2011-03-28

388

Nuclear Magnetic Resonance Solution Structure of the Escherichia coli DNA Polymerase III ? Subunit†  

PubMed Central

The catalytic core of Escherichia coli DNA polymerase III holoenzyme contains three subunits: ?, ?, and ?. The ? subunit contains the polymerase, and the ? subunit contains the exonucleolytic proofreading function. The small (8-kDa) ? subunit binds only to ?. Its function is not well understood, although it was shown to exert a small stabilizing effect on the ? proofreading function. In order to help elucidate its function, we undertook a determination of its solution structure. In aqueous solution, ? yielded poor-quality nuclear magnetic resonance spectra, presumably due to conformational exchange and/or protein aggregation. Based on our recently determined structure of the ? homolog from bacteriophage P1, named HOT, we constructed a homology model of ?. This model suggested that the unfavorable behavior of ? might arise from exposed hydrophobic residues, particularly toward the end of ?-helix 3. In gel filtration studies, ? elutes later than expected, indicating that aggregation is potentially responsible for these problems. To address this issue, we recorded 1H-15N heteronuclear single quantum correlation (HSQC) spectra in water-alcohol mixed solvents and observed substantially improved dispersion and uniformity of peak intensities, facilitating a structural determination under these conditions. The structure of ? in 60/40 (vol/vol) water-methanol is similar to that of HOT but differs significantly from a previously reported ? structure. The new ? structure is expected to provide additional insight into its physiological role and its effect on the ? proofreading subunit.

Mueller, Geoffrey A.; Kirby, Thomas W.; DeRose, Eugene F.; Li, Dawei; Schaaper, Roel M.; London, Robert E.

2005-01-01

389

Solution Structures of Spinach Acyl Carrier Protein with Decanoate and Stearate†  

PubMed Central

Acyl carrier protein (ACP) is a cofactor in a variety of biosynthetic pathways, including fatty acid metabolism. Thus it is of interest to determine structures of physiologically relevant ACP-fatty acid complexes. We report here the NMR solution structures of spinach ACP with decanoate (10:0-ACP) and stearate (18:0-ACP) attached to the 4? phosphopantetheine prosthetic group. The protein in the fatty acid complexes adopts a single conformer, unlike apo- and holo-ACP, which interconvert in solution between two major conformers. The protein component of both 10:0- and 18:0-ACP adopts the four-helix bundle topology characteristic of ACP, and a fatty acid binding cavity was identified in both structures. Portions of the protein close in space to the fatty acid and the 4? phosphopantetheine were identified using filtered/edited NOESY experiments. A docking protocol was used to generate protein structures containing bound fatty acid for 10:0- and 18:0-ACP. In both cases, the predominant structure contained fatty acid bound down the center of the helical bundle, in agreement with the location of the fatty acid binding pockets. These structures demonstrate the conformational flexibility of spinach-ACP and suggest how the protein changes to accommodate its myriad binding partners.

Zornetzer, Gregory A.; Fox, Brian G.; Markley, John L.

2008-01-01

390

The NMR solution structure of the pheromone Er-2 from the ciliated protozoan Euplotes raikovi.  

PubMed Central

The NMR structure of the pheromone Er-2 from the ciliated protozoan Euplotes raikovi has been determined in aqueous solution. The structure of this 40-residue protein was calculated with the distance geometry program DIANA from 621 distance constraints and 89 dihedral angle constraints; the program OPAL was employed for the energy minimization. For a group of 20 conformers used to characterize the solution structure, the average pairwise RMS deviation from the mean structure calculated for the backbone heavy atoms N, C alpha, and C' of residues 3-37 was 0.31 A. The molecular architecture is dominated by an up-down-up bundle of 3 short helices of residues 5-11, 14-20, and 23-33, which is similar to the structures of the homologous pheromones Er-1 and Er-10. Novel structural features include a well-defined N-cap on the first helix, a 1-residue deletion in the second helix resulting in the formation of a 3(10)-helix rather than an alpha-helix as found in Er-1 and Er-10, and the simultaneous presence of 2 different conformations for the C-terminal tetrapeptide segment, i.e., a major conformation with the Leu 39-Pro 40 peptide bond in the trans form and a minor conformation with this peptide bond in the cis form.

Ottiger, M.; Szyperski, T.; Luginbuhl, P.; Ortenzi, C.; Luporini, P.; Bradshaw, R. A.; Wuthrich, K.

1994-01-01

391

A dielectric spectroscopic study of the disperse structure of asphaltene solutions at high pressures  

SciTech Connect

The disperse structure of oil asphaltenes in benzene and toluene solutions at different temperatures and concentrations were studied at pressures up to 1.0 GPa. The polarity of the asphaltene molecules allows the dielectric spectroscopic method to be used. A sharp increase in the relaxation time and the sizes of the asphaltene aggregates, calculated according to the Debye model near the phase transition point, were found in the benzene solution. The pressure value corresponding to crystallization is much higher in the toluene solution, and only the border region can be investigated. An explanation of the pressure dependences of the relaxation times are presented. The activation energies and the coefficients of isothermal compressibility are calculated.

Syunyaev, R.Z.; Sh. Abid, R. [Gubkin Oil and Gas Institute, Moscow (Russian Federation)

1994-03-01

392

A structural study of the intermolecular interactions of tyramine in the solid state and in solution  

NASA Astrophysics Data System (ADS)

The nature of the interactions between tyramine units was investigated in the solid state and in solution. Crystals of tyramine in its free base form were analyzed by Fourier transform infrared (FT-IR) spectroscopy and single-crystal X-ray diffraction (XRD). The crystal structure shows a linear molecular organization held together by "head-to-tail" intermolecular hydrogen bonds between the amino groups and the phenolic hydroxyl groups. These chains are arranged in double layers that can geometrically favor the formation of templates in solution, which may facilitate macrocyclization reactions to form azacyclophane-type compounds. Computational calculations using the PM6-DH+ method and electrospray ionization mass spectrometry (ESI-HRMS) reveal that the formation of a hydrogen-bonded tyramine dimer is favored in solution.

Quevedo, Rodolfo; Nuñez-Dallos, Nelson; Wurst, Klaus; Duarte-Ruiz, Álvaro

2012-12-01

393

Liquid crystalline ordering of nucleosome core particles under macromolecular crowding conditions: evidence for a discotic columnar hexagonal phase.  

PubMed Central

Macromolecular crowding conditions occurring inside the cell nucleus were reproduced experimentally with solutions of mononucleosome core particles to study their supramolecular organization. We report here that under these conditions, and over a large range of monovalent salt concentrations, mononucleosome core particles self-assemble to form a discotic liquid crystalline phase characterized in polarizing and freeze-fracture electron microscopy. Mononucleosomes are stacked on each other to form columns, which are themselves closely packed into an hexagonal array. The nucleosome concentration, estimated from the network parameters, falls in the range of values measured in cell nuclei. We suggest that these concentrated solutions, although their organization cannot be immediately compared to the organization of chromatin in vivo, may be used to investigate the nucleosome-nucleosome interactions. Furthermore, this approach may be complexified to take into account the complexity of the eucaryotic chromatin. Images FIGURE 1 FIGURE 2 FIGURE 4

Leforestier, A; Livolant, F

1997-01-01

394

On macromolecular refinement at subatomic resolution with interatomic scatterers  

PubMed Central

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

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

2007-01-01

395

Blood flow and macromolecular transport in complex blood vessels.  

PubMed

Numerical simulations of pulsatile flows and macromolecular (such as LDL) transport in complex blood vessels, including the cerebral artery, are carried out using the FLUENT software. The hemodynamic factors such as axial velocity, secondary flow as well as LDL concentration distribution in the complex vessel are obtained. It is found that in the case of pulsatile flow, the LDL concentration is higher in the central region of the flow than on the wall. Under the precondition of impermeability, the numerical results indicate that the blood flow is quite complicated in complex blood vessel. The complex flow can reduce the LDL concentration on the vessel wall, which is helpful to prevent the concentration polarization. PMID:17767985

Hong, Jinxing; Wei, Lan; Fu, Ceji; Tan, Wenchang

2007-09-04

396

GMCT : a Monte Carlo simulation package for macromolecular receptors.  

PubMed

Generalized Monte Carlo titration (GMCT) is a versatile suite of computer programs for the efficient simulation of complex macromolecular receptor systems as for example proteins. The computational model of the system is based on a microstate description of the receptor and an average description of its surroundings in terms of chemical potentials. The receptor can be modeled in great detail including conformational flexibility and many binding sites with multiple different forms that can bind different ligand types. Membrane embedded systems can be modeled including electrochemical potential gradients. Overall properties of the receptor as well as properties of individual sites can be studied with a variety of different Monte Carlo (MC) simulation methods. Metropolis MC, Wang-Landau MC and efficient free energy calculation methods are included. GMCT is distributed as free open source software at www.bisb.uni-bayreuth.de under the terms of the GNU Affero General Public License. PMID:22278916

Ullmann, R Thomas; Ullmann, G Matthias

2012-01-25

397

On macromolecular refinement at subatomic resolution withinteratomic scatterers  

SciTech Connect

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

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

2007-11-09

398

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

PubMed Central

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

Day, J.; McPherson, A.

1992-01-01

399

Metabolism of macromolecular heparin in mouse neoplastic mast cells.  

PubMed Central

1. Polysaccharide in a heparin-producing mouse mastocytoma was pulse-labelled in vivo with [35S] sulphate, and after various periods of time was isolated from subcellular fractions. Such fractions were recovered from tissue homogenates by consecutive centrifugations at 1000g for 10min, 20000g for 20min and 100000g for 1h. Initially the 35S-labelled polysaccharide formed occurred principally in the second centrifugal fraction (20000g precipitate), with small amounts in the first (granular) and third (microsomal) fractions. Analysis for glycosyltransferase activity confirmed that glycosaminoglycans were formed chiefly in particles sedimenting at 20000g. Molecules of this newly synthesized polysaccharide were considerably larger than those of commercially available heparin, as judged from gel chromatography. 2. Within the first hour after injection of [35S]sulphate, most of the labelled polysaccharide was redistributed from the second to the first centrifugal fraction. During, and possibly also after, this shift, the macromolecular polysaccharide was degraded, ultimately to the size of commercial heparin. The degradation process appeared complete 6h after injection of [35S]sulphate. 3. Particulate subcellular fractions were incubated with macromolecular [35S]heparin and the products were analysed by gel chromatography. Significant degradation of the substrate occurred only with the second centrifugal fraction. Further characterization of this fraction, by density-gradient centrifugation in iso-osmotic colloidal silica, revealed a single visible band of particles, at approximately the same density at lysosomes. This band contained all the beta-glucuronidase, 35S-labelled endogenous polysacchride and heparin-degrading enzyme present in the second fraction.

Ogren, S; Lindahl, U

1976-01-01

400

Ions in water: The microscopic structure of a concentrated HCl solution  

NASA Astrophysics Data System (ADS)

A neutron diffraction experiment with isotopic H/D substitution on a concentrated HCl/H2O solution is presented. The full set of partial structure factors is extracted, by combining the diffraction data with a Monte Carlo simulation. This allows us to investigate both the changes of the water structure in the presence of ions and their solvation shell, overcoming the limitations of standard diffraction experiments. It is found that the interaction with the solutes affects the tetrahedral network of hydrogen bonded water molecules, in a manner similar to the application of an external pressure to pure water, although HCl seems less effective than other solutes, such as NaOH, at the same concentration. Consistent with experimental and theoretical data, the number of water molecules in the solution is not sufficient to completely dissociate the acid molecule. As a consequence, both dissociated H+ and Cl- ions and undissociated HCl molecules coexist in the sample, and this mixture is correctly reproduced in the simulation box. In particular, the hydrated H+ ions, forming a H3O+ complex, participate in three strong and short hydrogen bonds, while a well-defined hydration shell is found around the chlorine ion. These results are not consistent with the findings of early diffraction experiments on the same system and could only be obtained by combining high quality experimental data with a proper computer simulation.

Botti, A.; Bruni, F.; Imberti, S.; Ricci, M. A.; Soper, A. K.

2004-10-01

401

Similarity solutions for the structure of supernova blast waves driven by clumped ejecta. I. Undecelerated clumps  

SciTech Connect

New similarity solutions are presented for the structure of supernova blast waves driven by clumped supernova ejecta. The solutions are obtained using a spherically symmetric two-fluid hydrodynamic model in which clumps of ejecta stream through diffuse background gas. The clumps couple to the diffuse gas through mass ablation and the associated momentum and energy transfer. The most striking difference between these solutions and previous solutions is that clumps may move ahead of the shock front in the ambient medium, leading a precursor which heats the medium in advance of the main shock. The results appear to provide a natural explanation for the X-ray halo seen in Cas A and for various other aspects of the morphology of this supernova remnant. The difference between Cas A and remnants such as Tycho, in which clumps of ejecta are only observed within the confines of an interstellar shock front, may be explained by differences in evolutionary epoch, or differences in the structure of the ambient medium, or intrinsic differences in the clumps.

Hamilton, A.J.S.

1985-04-15

402

Averaged solute transport during solidification of a binary mixture: Active dispersion in dendritic structures  

NASA Astrophysics Data System (ADS)

The macroscopic conservation equations governing solute transport during solidification of binary alloys are derived using an averaging procedure in the context of macroscale nonequilibrium. Special attention is focused on the derivation of the associated closure problems, leading to the determination of the effective dispersion tensor and macroscopic interphase coefficients that characterize active dispersion phenomena. These closure problems are solved numerically using schematic structures and digitized images of real columnar dendritic structures observed experimentally during solidification of succinonitrile-4 wt pct acetone. The influence of the geometry and dispersion on the effective solute-properties transport is analyzed, and comparison with passive dispersion is provided. The theoretical and numerical results indicate, first, that tortuosity effects are small, and this is related to the impact of the boundary condition at the interface between the two phases, and, second, that dispersion becomes very important only at very large Péclet numbers.

Bousquet-Melou, P.; Neculae, A.; Goyeau, B.; Quintard, M.

2002-06-01

403

A deformation of Sasakian structure in the presence of torsion and supergravity solutions  

NASA Astrophysics Data System (ADS)

A deformation of Sasakian structure in the presence of totally skew-symmetric torsion is discussed on odd-dimensional manifolds whose metric cones are Kähler with torsion. It is shown that such a geometry inherits similar properties to those of Sasakian geometry. As their example, we present an explicit expression of local metrics. It is also demonstrated that our example of the metrics admits the existence of hidden symmetry described by non-trivial odd-rank generalized closed conformal Killing-Yano tensors. Furthermore, using these metrics as an ansatz, we construct exact solutions in five-dimensional minimal gauged/ungauged supergravity and 11-dimensional supergravity. Finally, the global structures of the solutions are discussed. We obtain regular metrics on compact manifolds in five dimensions, which give natural generalizations of Sasaki-Einstein manifolds Yp, q and La, b, c. We also briefly discuss regular metrics on non-compact manifolds in 11 dimensions.

Houri, Tsuyoshi; Takeuchi, Hiroshi; Yasui, Yukinori

2013-07-01

404

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

SciTech Connect

A purpose-built spectroelectrochemical cell for in situ fluorescence XAFS (X-ray Absorption Fine Structure) measurements of bulk solution species during constant-potential electrolysis is described. The cell performance was demonstrated by the collection of europium L{sub 3}-edge XANES (X-ray Absorption Near Edge Structure) throughout the course of electrolysis of an aqueous solution of EuCl{sub 3}{center_dot}6H{sub 2}O in 1 M H{sub 2}SO{sub 4}. The europium L{sub 3}-edge resonances reported here for the Eu{sup III} and Eu{sup II} ions demonstrate that their 2p{sub 3/2} {yields} 5d electronic transition probabilities are not the same.

Antonio, M.R.; Soderholm, L. [Argonne National Lab., IL (United States). Chemistry Div.; Song, I. [Case Western Reserve Univ., Cleveland, OH (United States)

1995-06-12

405

Structural evolution of water swollen perfluorosulfonated ionomers from dry membrane to solution  

Microsoft Academic Search

The structural evolution of perfluorosulfonated ionomer (PFSI) membranes from dry materials to highly swollen membranes and solutions was investigated using mainly small-angle scattering techniques. The small-angle scattering maximum (“ionomer peak”) is shown to be observable up to very large water content and shifts continuously toward small-angle as water content increases. A modification of the swelling process is observed for a

G. Gebel

2000-01-01

406

Solution Structure, Stability, and Nucleic Acid Binding of the Hyperthermophile Protein Sso10b2 † , ‡  

Microsoft Academic Search

The Sso10b (or Alba) family of proteins is a conserved group of archaeal and eukaryotic proteins which are thought to play a role in both chromatin organization and RNA metabolism. We describe here the solution structure and properties of Sso10b2 from Sulfolobus solfataricus. NMR data including residual dipolar couplings and 15N relaxation data demonstrated that the protein adopts a ‚1R1‚2R2‚3‚4

Kalpesh Biyani; Mebrahtu A. Kahsai; Andrew T. Clark; Tracy L. Armstrong; Stephen P. Edmondson; John W. Shriver

2005-01-01

407

Solution Structure of a Two-Base DNA Bulge Complexed with an Enediyne Cleaving Analog  

Microsoft Academic Search

Nucleic acid bulges have been implicated in a number of biological processes and are specific cleavage targets for the enediyne antitumor antibiotic neocarzinostatin chromophore in a base-catalyzed, radical-mediated reaction. The solution structure of the complex between an analog of the bulge-specific cleaving species and an oligodeoxynucleotide containing a two-base bulge was elucidated by nuclear magnetic resonance. An unusual binding mode

Adonis Stassinopoulos; Jie Ji; Xiaolian Gao; Irving H. Goldberg

1996-01-01

408

Synthesis of partially exfoliated EPDM\\/LDH nanocomposites by solution intercalation: Structural characterization and properties  

Microsoft Academic Search

Partially exfoliated ethylene propylene diene terpolymer (EPDM)\\/Mg–Al layered double hydroxide (LDH) nanocomposites have been synthesized by solution intercalation using organically modified LDH (DS-LDH) as nanofiller obtained by reconstruction method using sodium dodecyl sulfate and LDH. The nanocomposite structure has been elucidated by the X-ray diffraction (XRD), transmission electron microscopy (TEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR) spectroscopy and

H. Acharya; S. K. Srivastava; Anil K. Bhowmick

2007-01-01

409

Differences in the solution structures of the parallel ?-helical pectate lyases as determined by limited proteolysis  

Microsoft Academic Search

The pectate lyase family of proteins has been shown to fold into a novel domain motif, the right-handed parallel ?-helix. As a means of gaining insight to the solution structure of the pectate lyases, the enzymes were subjected to limited proteolytic digestion by the endoproteases AspN, GluC and trypsin. The effects of proteolytic cleavage on enzymatic activity were determined, and

Jason C. Hurlbert; James F Preston

2002-01-01

410

Solution Structure of a Low-Molecular-Weight Protein Tyrosine Phosphatase from Bacillus subtilis  

Microsoft Academic Search

Received 18 July 2005\\/Accepted 14 November 2005 The low-molecular-weight (LMW) protein tyrosine phosphatases (PTPs) exist ubiquitously in prokaryotes and eukaryotes and play important roles in cellular processes. We report here the solution structure of YwlE, an LMW PTP identified from the gram-positive bacteria Bacillus subtilis. YwlE consists of a twisted central four-stranded parallel -sheet with seven -helices packing on both

Huimin Xu; Bin Xia; Changwen Jin

2006-01-01

411

Absorption of nitrogen oxides in aqueous solutions in a structured packing pilot column  

Microsoft Academic Search

This study deals with the absorption of dilute nitrogen oxides (NOx) into aqueous solutions of hydrogen peroxide (0.05M) and of sodium hydroxide (2M), at the atmospheric pressure. A pilot column filled with structured the metallic packing Optiflow™ was employed. The feed gas was air containing NOx at concentrations between 121 and 1336Pa and the oxidation degrees were 0.5 and 1.

J. L. de Paiva; G. C. Kachan

2004-01-01

412

NMR solution structures of adducts derived from the binding of polycyclic aromatic diol epoxides to DNA  

SciTech Connect

Site-specifically modified oligonucleotides were derived from the reactions of stereoisomeric polycyclic aromatic diol epoxide metabolite model compounds with oligonucleotides of defined base composition and sequence. The NMR solution structures of ten different adducts studied so far are briefly described, and it is shown that stereochemical factors and the nature of the oligonucleotide context of the complementary strands, exert a powerful influence on the conformational features of these adducts.

Cosman, M.; Patel, D.J. [Memorial Sloan Kettering Cancer Center, New York, NY (United States). Cellular Biochemistry and Biophysics Program; Hingerty, B.E. [Oak Ridge National Lab., TN (United States). Health and Safety Research Div.; Amin, S. [American Health Foundation, Valhalla, NY (United States); Broyde, S.; Geacintov, N.E. [New York Univ., NY (United States)

1995-12-31

413

Structural modification of potato starch by solutions of nitrogen(IV) oxide in CCl 4  

Microsoft Academic Search

Structural transformations of potato starch by solutions of nitrogen(IV) oxide in CCl4 were studied as a function of oxidant concentration, starch moisture content, reaction time, and molar ratio of reactants.\\u000a Oxidized starches with various numbers of carboxylic acids were studied by x-ray phase analysis, 13C NMR, and IR spectroscopy. It was found that carboxylic acids were formed primarily on C6

S. M. Butrim; T. D. Bil’dyukevich; N. S. Butrim; T. L. Yurkshtovich

2007-01-01

414

Structural stability of yttria doped zirconia membranes in acid and basic aqueous solutions  

Microsoft Academic Search

Hydrothermal corrosion behaviour of yttria doped zirconia (3Y–ZrO2) microfiltration membranes was investigated in aqueous solutions of acids and bases at room temperature and 80°C in a static corrosion test. Unsupported membranes of 3Y–ZrO2 prepared by slip casting had 100% tetragonal structure after sintering at 1200°C. Weight loss, phase composition, porosity, pore size and surface area as well as residual stress

F Shojai; T. A Mäntylä

2001-01-01

415

Computer modeling of the local structure, mixing properties, and stability of binary oxide solid solutions with corundum structure  

NASA Astrophysics Data System (ADS)

An original technique of computer modeling of substitutional solid solutions has been applied to Al2O3-Cr2O3, Al2O3-Fe2O3, and Fe2O3-Cr2O3 binary systems. The parameters of semiempirical interatomic potentials were optimized using the experimentally studied structural, elastic, and thermodynamic properties of pure components. Among point defects, the most energetically favorable ones for all three oxides are Schottky vacancy quintets. To model ( M {x/1} M {1/- x 2})2O3 solid solutions, 4 × 4 × 1 disordered supercells with M 1: M 2 cation ratios of 1: 5, 1: 2, 1: 1, 2: 1, and 5: 1 have been constructed in the cation sublattice containing 192 atoms. The mixing enthalpy and volume, interaction parameters, bulk moduli, and vibrational entropy were found by minimizing the interatomic interaction energy in supercells with the symmetry P1. Calculations of the Gibbs energy made it possible to estimate the fields of stability of the Al2O3-Cr2O3 and Al2O3-Fe2O3 solid solutions; these estimates were compared with the experimental data. Histograms of M-M, M-O, and O-O interatomic distances were constructed and the local structure was analyzed for the Al1.0Cr1.0O3, Al1.0Fe1.0O3, and Fe1.0Cr1.0O3 compositions.

Eremin, N. N.; Talis, R. A.; Urusov, V. S.

2008-09-01

416

Effective protein-protein interaction from structure factor data of a lysozyme solution  

NASA Astrophysics Data System (ADS)

We report the determination of an effective protein-protein central potential for a lysozyme solution, obtained from the direct inversion of the total structure factor of the system, as extracted from small angle neutron scattering. The inversion scheme rests on a hypernetted-chain relationship between the effective potential and the structural functions, and is preliminarily tested for the case of a Lennard-Jones interaction. The characteristics of our potential are discussed in comparison with current models of effective interactions in complex fluids. The phase behavior predictions are also investigated.

Abramo, M. C.; Caccamo, C.; Cavero, M.; Costa, D.; Pellicane, G.; Ruberto, R.; Wanderlingh, U.

2013-08-01

417

Mechanical and structural properties of solution-cast high-amylose maize starch films.  

PubMed

Environmental issues have forced the introduction of sustainable solutions such as annually renewable resources being used as a raw material for packaging and disposables. This paper examined the effects of time and temperature during manufacturing and plasticiser content on the molecular structure of high-amylose maize starch films. It also analysed how manufacturing conditions, plasticiser content and molecular structure of the films affected their material properties. It was found that increased time or temperature increased the degradation of amylose and of amylopectin, which in turn negatively affected film cohesiveness. However, neither time nor temperature had any effect on tensile properties. PMID:19828118

Koch, Kristine; Gillgren, Thomas; Stading, Mats; Andersson, Roger

2009-10-12

418

The structure of nanochannels formed by block copolymer solutions confined in nanotubes  

NASA Astrophysics Data System (ADS)

Monte Carlo simulations are employed to obtain information about the radius and the roughness of the inner surface of the channels, which are generated by a family of block copolymer solutions confined in nanotubes. The fluctuations of the above quantities also have been calculated. The simulations have been carried out by varying the interactions between various kinds of segments and those between segments and the wall of the nanotubes, as well as the chemical structure of the copolymer and the nanotube diameter. The present simulations provide insight regarding the structure of ionic and water channels formed by protein in the phospholipid bilayers of the cell membrane.

Chen, Houyang; Ruckenstein, Eli

2009-09-01

419

Solution NMR structure of BT_0084, a conjugative transposon lipoprotein from Bacteroides thetaiotamicron  

PubMed Central

Here we describe the solution NMR structure of the 120 amino acid fragment of BT_0084, without the N-terminal lipoprotein targeting sequence, encoded in a conjugative transposon (CTn) in the genome of Bacteroides thetaiotamicron. BT_0084 belongs to a conserved family of TraQ lipoproteins that are encoded at the end of the tra operon, which contains genes essential for transfer of CTns. The structure belongs to the immunoglobulin superfamily and shares structural similarity, albeit low sequence identity (< 15%), to other proteins involved in pili production for bacterial cell attachment. Although its role in repression of CTn transfer remains to be determined, the structure of BT_0084 reported here represents the first from the Bacteroides TraQ family and should facilitate further understanding of the tra operon-regulated transfer of CTns.

Ramelot, Theresa A.; Yang, Yunhuang; Xiao, Rong; Acton, Thomas B.; Everett, John K.; Montelione, Gaetano T.; Kennedy, Michael A.

2013-01-01

420

Structure and dimerization of translation initiation factor aIF5B in solution  

SciTech Connect

Translation initiation factor 5B (IF5B) is required for initiation of protein synthesis. The solution structure of archaeal IF5B (aIF5B) was analysed by small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS) and was indicated to be in both monomeric and dimeric form. Sedimentation equilibrium (SE) analytical ultracentrifugation (AUC) of aIF5B indicated that aIF5B forms irreversible dimers in solution but only to a maximum of 5.0-6.8% dimer. Sedimentation velocity (SV) AUC at higher speed also indicated the presence of two species, and the sedimentation coefficients s{sub 20,w}{sup 0} were determined to be 3.64 and 5.51 {+-} 0.29 S for monomer and dimer, respectively. The atomic resolution (crystallographic) structure of aIF5B (Roll-Mecak et al. [6]) was used to model monomer and dimer, and theoretical sedimentation coefficients for these models were computed (3.89 and 5.63 S, respectively) in good agreement with the sedimentation coefficients obtained from SV analysis. Thus, the structure of aIF5B in solution must be very similar to the atomic resolution structure of aIF5B. SAXS data were acquired in the same buffer with the addition of 2% glycerol to inhibit dimerization, and the resultant monomeric aIF5B in solution did indeed adopt a structure very similar to the one reported earlier for the protein in crystalline form. The p(r) function indicated an elongated conformation supported by a radius of gyration of 37.5 {+-} 0.2 {angstrom} and a maximum dimension of {approx}130 {angstrom}. The effects of glycerol on the formation of dimers are discussed. This new model of aIF5B in solution shows that there are universal structural differences between aIF5B and the homologous protein IF2 from Escherichia coli.

Carø VohlanderRasmussen, Louise; Oliveira, Cristiano Luis Pinto; Byron, Olwyn; Jensen, Janni Mosgaard; Pedersen, Jan Skov; Sperling-Petersen, Hans Uffe; Mortensen, Kim Kusk (Aarhus); (Glasgow)

2012-02-07