scholarly journals In crystallo optical spectroscopy as a complementary tool to crystallography

2014 ◽  
Vol 70 (a1) ◽  
pp. C1530-C1530
Author(s):  
Antoine Royant
Keyword(s):  
Structural Biology ◽  
Structural Data ◽  
Portable Devices ◽  
X Ray Crystallography ◽  
The Status ◽  
On Line ◽  
Complementary Techniques ◽  
Year 2000 ◽  
Scientific Questions ◽  
Biology Group

The analysis of structural data obtained by X-ray crystallography benefits from information obtained from complementary techniques, especially if these are applied to the crystals themselves. As a consequence, optical spectroscopies as applied in Structural Biology have become instrumental in assessing the relevance of many crystallographic results. Since the year 2000, such data can be recorded close to, or directly on, the Structural Biology Group beamlines of the ESRF. A core laboratory featuring various spectrometers, named the Cryobench, is now in its third version and houses portable devices that can be directly mounted on beamlines. This presentation will report the status of the current version of the Cryobench, now located on the MAD beamline ID29 and thus called ID29S-Cryobench, S standing for 'Spectroscopy'. In particular, the new on-line Raman data collection mode of ID29 will be described. Finally, it will review the diverse experiments that can be performed at the Cryobench, highlighting various scientific questions that can be addressed.

scholarly journals In crystallooptical spectroscopy (icOS) as a complementary tool on the macromolecular crystallography beamlines of the ESRF

2015 ◽  
Vol 71 (1) ◽  
pp. 15-26 ◽  
Author(s):  
David von Stetten ◽  
Thierry Giraud ◽  
Philippe Carpentier ◽  
Franc Sever ◽  
Maxime Terrien ◽  
...  
Keyword(s):  
Structural Biology ◽  
Structural Data ◽  
Current Status ◽  
Portable Devices ◽  
X Ray ◽  
X Ray Crystallography ◽  
Complementary Techniques ◽  
Year 2000 ◽  
Scientific Questions ◽  
Biology Group

The analysis of structural data obtained by X-ray crystallography benefits from information obtained from complementary techniques, especially as applied to the crystals themselves. As a consequence, optical spectroscopies in structural biology have become instrumental in assessing the relevance and context of many crystallographic results. Since the year 2000, it has been possible to record such data adjacent to, or directly on, the Structural Biology Group beamlines of the ESRF. A core laboratory featuring various spectrometers, named the Cryobench, is now in its third version and houses portable devices that can be directly mounted on beamlines. This paper reports the current status of the Cryobench, which is now located on the MAD beamline ID29 and is thus called the ID29S-Cryobench (where S stands for `spectroscopy'). It also reviews the diverse experiments that can be performed at the Cryobench, highlighting the various scientific questions that can be addressed.

scholarly journals An Open Source Mesh Generation Platform for Biophysical Modeling Using Realistic Cellular Geometries

2019 ◽  
Author(s):  
Christopher T. Lee ◽  
Justin G. Laughlin ◽  
John B. Moody ◽  
Rommie E. Amaro ◽  
J. Andrew McCammon ◽  
...  
Keyword(s):  
Structural Biology ◽  
Mesh Generation ◽  
Structural Information ◽  
Electron Tomography ◽  
Structural Data ◽  
Biophysical Modeling ◽  
X Ray Crystallography ◽  
Biophysical Models ◽  
Geometric Mesh ◽  
And Mathematics

ABSTRACTAdvances in imaging methods such as electron microscopy, tomography, and other modalities are enabling high-resolution reconstructions of cellular and organelle geometries. Such advances pave the way for using these geometries for biophysical and mathematical modeling once these data can be represented as a geometric mesh, which, when carefully conditioned, enables the discretization and solution of partial differential equations. In this study, we outline the steps for a naïve user to approach GAMer 2, a mesh generation code written in C++ designed to convert structural datasets to realistic geometric meshes, while preserving the underlying shapes. We present two example cases, 1) mesh generation at the subcellular scale as informed by electron tomography, and 2) meshing a protein with structure from x-ray crystallography. We further demonstrate that the meshes generated by GAMer are suitable for use with numerical methods. Together, this collection of libraries and tools simplifies the process of constructing realistic geometric meshes from structural biology data.SIGNIFICANCEAs biophysical structure determination methods improve, the rate of new structural data is increasing. New methods that allow the interpretation, analysis, and reuse of such structural information will thus take on commensurate importance. In particular, geometric meshes, such as those commonly used in graphics and mathematics, can enable a myriad of mathematical analysis. In this work, we describe GAMer 2, a mesh generation library designed for biological datasets. Using GAMer 2 and associated tools PyGAMer and BlendGAMer, biologists can robustly generate computer and algorithm friendly geometric mesh representations informed by structural biology data. We expect that GAMer 2 will be a valuable tool to bring realistic geometries to biophysical models.

scholarly journals Structural biology in the time of COVID-19: perspectives on methods and milestones

IUCrJ ◽  
2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Miranda L. Lynch ◽  
Edward H. Snell ◽  
Sarah E. J. Bowman
Keyword(s):  
Structural Biology ◽  
Protein Structures ◽  
50Th Anniversary ◽  
Data Bank ◽  
World Health ◽  
X Ray Crystallography ◽  
The Status ◽  
One Year ◽  
Health Organization ◽  
Structural Methods

The global COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has wreaked unprecedented havoc on global society, in terms of a huge loss of life and burden of morbidity, economic upheaval and social disruption. Yet the sheer magnitude and uniqueness of this event has also spawned a massive mobilization of effort in the scientific community to investigate the virus, to develop therapeutics and vaccines, and to understand the public health impacts. Structural biology has been at the center of these efforts, and so it is advantageous to take an opportunity to reflect on the status of structural science vis-à-vis its role in the fight against COVID-19, to register the unprecedented response and to contemplate the role of structural biology in addressing future outbreak threats. As the one-year anniversary of the World Health Organization declaration that COVID-19 is a pandemic has just passed, over 1000 structures of SARS-CoV-2 biomolecules have been deposited in the Worldwide Protein Data Bank (PDB). It is rare to obtain a snapshot of such intense effort in the structural biology arena and is of special interest as the 50th anniversary of the PDB is celebrated in 2021. It is additionally timely as it overlaps with a period that has been termed the `resolution revolution' in cryoelectron microscopy (CryoEM). CryoEM has recently become capable of producing biomolecular structures at similar resolutions to those traditionally associated with macromolecular X-ray crystallography. Examining SARS-CoV-2 protein structures that have been deposited in the PDB since the virus was first identified allows a unique window into the power of structural biology and a snapshot of the advantages of the different techniques available, as well as insight into the complementarity of the structural methods.

scholarly journals Analysis of the Quality of Macromolecular Structures

2017 ◽  
Author(s):  
Dinakar M. Salunke
Keyword(s):  
Structural Biology ◽  
Model Building ◽  
Structural Data ◽  
Data Bank ◽  
X Ray Crystallography ◽  
Structure Factors ◽  
Scientific Systems ◽  
Published Research

AbstractStructure determination utilizing X-ray crystallography involves collection of diffraction data, determination of initial phases followed by iterative rounds of model building and crystallographic refinement to improve the phases and minimize the differences between calculated and observed structure factors. At each of these stages, a variety of statistical filters exist to ensure appropriate validation. Biologically important observations often come from interpretations of signals that need to be carefully deciphered from noise and therefore human intervention is as important as the automated filters. Currently, all structural data are deposited in the Protein Data Bank and this repository is continuously evolving to incorporate possible new improvements in macromolecular crystallography. The journals that publish data arising from structural studies modulate their policies to take cognizance of new improved methodologies. The PDB and journals have evolved an accepted protocol to ensure the integrity of crystallographic results. As a result, the quality of available data and interpretations are becoming better over the years. However, there have been periodic efforts by some individuals who misuse validation mechanisms to selectively target published research through spurious challenges. These actions do more harm to the field of structural biology and runs counter to their claim to cleanse the system. The scientific systems in structural biology are robust and capable of self-correction and unwarranted vigilantism is counterproductive.

scholarly journals Identification of V6.51L as a selectivity hotspot in stereoselective A2B adenosine receptor antagonist recognition

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xuesong Wang ◽  
Willem Jespers ◽  
Rubén Prieto-Díaz ◽  
Maria Majellaro ◽  
Adriaan P. IJzerman ◽  
...  
Keyword(s):  
Radioligand Binding ◽  
Structural Data ◽  
Binding Mode ◽  
Selective Recognition ◽  
Chiral Hplc ◽  
Binding Assays ◽  
Structural Determinants ◽  
X Ray Crystallography ◽  
Adenosine Receptor Antagonist ◽  
Energy Perturbation

AbstractThe four adenosine receptors (ARs) A1AR, A2AAR, A2BAR, and A3AR are G protein-coupled receptors (GPCRs) for which an exceptional amount of experimental and structural data is available. Still, limited success has been achieved in getting new chemical modulators on the market. As such, there is a clear interest in the design of novel selective chemical entities for this family of receptors. In this work, we investigate the selective recognition of ISAM-140, a recently reported A2BAR reference antagonist. A combination of semipreparative chiral HPLC, circular dichroism and X-ray crystallography was used to separate and unequivocally assign the configuration of each enantiomer. Subsequently affinity evaluation for both A2A and A2B receptors demonstrate the stereospecific and selective recognition of (S)-ISAM140 to the A2BAR. The molecular modeling suggested that the structural determinants of this selectivity profile would be residue V2506.51 in A2BAR, which is a leucine in all other ARs including the closely related A2AAR. This was herein confirmed by radioligand binding assays and rigorous free energy perturbation (FEP) calculations performed on the L249V6.51 mutant A2AAR receptor. Taken together, this study provides further insights in the binding mode of these A2BAR antagonists, paving the way for future ligand optimization.

scholarly journals Endo-fucoidan hydrolases from glycoside hydrolase family 107 (GH107) display structural and mechanistic similarities to α-l-fucosidases from GH29

2018 ◽  
Vol 293 (47) ◽  
pp. 18296-18308 ◽  
Author(s):  
Chelsea Vickers ◽  
Feng Liu ◽  
Kento Abe ◽  
Orly Salama-Alber ◽  
Meredith Jenkins ◽  
...  
Keyword(s):  
Glycoside Hydrolase ◽  
Biological Activities ◽  
Bacterial Species ◽  
Structural Data ◽  
Side Chain ◽  
Glycoside Hydrolase Family ◽  
X Ray Crystallography ◽  
Catalytic Mechanisms ◽  
Thickening Agents ◽  
Hydrolase Family

Fucoidans are chemically complex and highly heterogeneous sulfated marine fucans from brown macro algae. Possessing a variety of physicochemical and biological activities, fucoidans are used as gelling and thickening agents in the food industry and have anticoagulant, antiviral, antitumor, antibacterial, and immune activities. Although fucoidan-depolymerizing enzymes have been identified, the molecular basis of their activity on these chemically complex polysaccharides remains largely uninvestigated. In this study, we focused on three glycoside hydrolase family 107 (GH107) enzymes: MfFcnA and two newly identified members, P5AFcnA and P19DFcnA, from a bacterial species of the genus Psychromonas. Using carbohydrate-PAGE, we show that P5AFcnA and P19DFcnA are active on fucoidans that differ from those depolymerized by MfFcnA, revealing differential substrate specificity within the GH107 family. Using a combination of X-ray crystallography and NMR analyses, we further show that GH107 family enzymes share features of their structures and catalytic mechanisms with GH29 α-l-fucosidases. However, we found that GH107 enzymes have the distinction of utilizing a histidine side chain as the proposed acid/base catalyst in its retaining mechanism. Further interpretation of the structural data indicated that the active-site architectures within this family are highly variable, likely reflecting the specificity of GH107 enzymes for different fucoidan substructures. Together, these findings begin to illuminate the molecular details underpinning the biological processing of fucoidans.

Uses of content analysis in economic sciences: An overview of the current situation and prospects

2021 ◽  
pp. 79-95
Author(s):  
A. N. Oleinik
Keyword(s):  
Content Analysis ◽  
Mixed Methods ◽  
Qualitative Data ◽  
Web Of Science ◽  
Current Situation ◽  
Economic Information ◽  
The Status ◽  
On Line ◽  
The Creation

The article discusses the status of quantitative and qualitative data in economic sciences, as well as methods for transforming data into information and knowledge. Particular attention is devoted to content analysis as a set of methods for aggregating, processing and analyzing qualitative data; its forms (qualitative, quantitative and mixed methods) and uses by economists. Content analysis appears to be particularly suitable for non-orthodox economists because of their refusal to consider price as the only source of economic information. The content analysis of metadata of articles indexed in Web of Science and eLibrary suggests that Russian economists still have insufficient familiarity with the principles of content analysis and their applications to research compared with their Western counterparts. It is argued that the creation of on-line platforms for content analysis and on-line banks of qualitative data may become a trigger for changing this situation.

Examining the structure of the mature amyloid fibril

2002 ◽  
Vol 30 (4) ◽  
pp. 521-525 ◽  
Author(s):  
O. S. Makin ◽  
L. C. Serpell
Keyword(s):  
Self Assembly ◽  
Rational Design ◽  
Amyloid Fibrils ◽  
Structural Information ◽  
X Ray ◽  
X Ray Crystallography ◽  
Cryo Electron Microscopy ◽  
Fibre Diffraction ◽  
Complementary Techniques ◽  
Mature Fibril

The pathogenesis of the group of diseases known collectively as the amyloidoses is characterized by the deposition of insoluble amyloid fibrils. These are straight, unbranching structures about 70–120 å (1 å = 0.1 nm) in diameter and of indeterminate length formed by the self-assembly of a diverse group of normally soluble proteins. Knowledge of the structure of these fibrils is necessary for the understanding of their abnormal assembly and deposition, possibly leading to the rational design of therapeutic agents for their prevention or disaggregation. Structural elucidation is impeded by fibril insolubility and inability to crystallize, thus preventing the use of X-ray crystallography and solution NMR. CD, Fourier-transform infrared spectroscopy and light scattering have been used in the study of the mechanism of fibril formation. This review concentrates on the structural information about the final, mature fibril and in particular the complementary techniques of cryo-electron microscopy, solid-state NMR and X-ray fibre diffraction.

Idiom as the intersection of conceptual and syntactic schemas

2014 ◽  
Vol 6 (4) ◽  
pp. 492-509 ◽  
Author(s):  
DANIEL SANFORD
Keyword(s):  
Frequency Effects ◽  
Token Frequency ◽  
Metaphor Theory ◽  
Idiomatic Expressions ◽  
The Status ◽  
On Line ◽  
Key Issues ◽  
Idiomatic Meaning

abstractTwo key issues in the study of idiom are the metaphorical status of idioms (whether or not underlying metaphors are active in the on-line processing of figurative idiomatic expressions) and the compositional status of idioms (whether or not the overall meaning of such expressions is analyzable from internal elements). This study addresses these questions from the perspective of emergent metaphor theory (Sanford, 2012, 2013), arguing that key properties of such expressions − idiosyncrasy of both form and meaning, the potential for idiom to be manipulated in discourse, and diachronic patterns in changes of idiomatic meaning − follow from the status of metaphorical idioms as highly entrenched instances of both conceptual and syntactic mappings. In the case of both types of schema, the interaction of type and token frequency effects predict the metaphoricity and analyzability of idioms.

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