macromolecular structure
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Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) play a crucial role in structure-guided drug discovery and design, and also provide atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. The quality with which small-molecule ligands have been modelled in Protein Data Bank (PDB) entries has been, and continues to be, a matter of concern for many investigators. Correctly interpreting whether electron density found in a binding site is compatible with the soaked or co-crystallized ligand or represents water or buffer molecules is often far from trivial. The Worldwide PDB validation report (VR) provides a mechanism to highlight any major issues concerning the quality of the data and the model at the time of deposition and annotation, so the depositors can fix issues, resulting in improved data quality. The ligand-validation methods used in the generation of the current VRs are described in detail, including an examination of the metrics to assess both geometry and electron-density fit. It is found that the LLDF score currently used to identify ligand electron-density fit outliers can give misleading results and that better ligand-validation metrics are required.
- MeSH
- databáze proteinů * MeSH
- konformace proteinů * MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- ligandy MeSH
- makromolekulární látky chemie MeSH
- molekulární modely MeSH
- molekulární struktura MeSH
- proteiny analýza chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
Segmentation helps interpret imaging data in a biological context. With the development of powerful tools for automated segmentation, public repositories for imaging data have added support for sharing and visualizing segmentations, creating the need for interactive web-based visualization of 3D volume segmentations. To address the ongoing challenge of integrating and visualizing multimodal data, we developed Mol* Volumes and Segmentations (Mol*VS), which enables the interactive, web-based visualization of cellular imaging data supported by macromolecular data and biological annotations. Mol*VS is fully integrated into Mol* Viewer, which is already used for visualization by several public repositories. All EMDB and EMPIAR entries with segmentation datasets are accessible via Mol*VS, which supports the visualization of data from a wide range of electron and light microscopy experiments. Additionally, users can run a local instance of Mol*VS to visualize and share custom datasets in generic or application-specific formats including volumes in .ccp4, .mrc, and .map, and segmentations in EMDB-SFF .hff, Amira .am, iMod .mod, and Segger .seg. Mol*VS is open source and freely available at https://molstarvolseg.ncbr.muni.cz/.
The Protein Data Bank in Europe (PDBe), a founding member of the Worldwide Protein Data Bank (wwPDB), actively participates in the deposition, curation, validation, archiving and dissemination of macromolecular structure data. PDBe supports diverse research communities in their use of macromolecular structures by enriching the PDB data and by providing advanced tools and services for effective data access, visualization and analysis. This paper details the enrichment of data at PDBe, including mapping of RNA structures to Rfam, and identification of molecules that act as cofactors. PDBe has developed an advanced search facility with ∼100 data categories and sequence searches. New features have been included in the LiteMol viewer at PDBe, with updated visualization of carbohydrates and nucleic acids. Small molecules are now mapped more extensively to external databases and their visual representation has been enhanced. These advances help users to more easily find and interpret macromolecular structure data in order to solve scientific problems.
- MeSH
- databáze proteinů * MeSH
- konformace proteinů MeSH
- shluková analýza MeSH
- software * MeSH
- správnost dat MeSH
- uživatelské rozhraní počítače MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
3D macromolecular structural data is growing ever more complex and plentiful in the wake of substantive advances in experimental and computational structure determination methods including macromolecular crystallography, cryo-electron microscopy, and integrative methods. Efficient means of working with 3D macromolecular structural data for archiving, analyses, and visualization are central to facilitating interoperability and reusability in compliance with the FAIR Principles. We address two challenges posed by growth in data size and complexity. First, data size is reduced by bespoke compression techniques. Second, complexity is managed through improved software tooling and fully leveraging available data dictionary schemas. To this end, we introduce BinaryCIF, a serialization of Crystallographic Information File (CIF) format files that maintains full compatibility to related data schemas, such as PDBx/mmCIF, while reducing file sizes by more than a factor of two versus gzip compressed CIF files. Moreover, for the largest structures, BinaryCIF provides even better compression-factor ten and four versus CIF files and gzipped CIF files, respectively. Herein, we describe CIFTools, a set of libraries in Java and TypeScript for generic and typed handling of CIF and BinaryCIF files. Together, BinaryCIF and CIFTools enable lightweight, efficient, and extensible handling of 3D macromolecular structural data.
- MeSH
- chemické databáze MeSH
- komprese dat metody MeSH
- krystalografie metody MeSH
- makromolekulární látky chemie ultrastruktura MeSH
- molekulární modely * MeSH
- software * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
The Complex Portal (www.ebi.ac.uk/complexportal) is a manually curated, encyclopaedic database that collates and summarizes information on stable, macromolecular complexes of known function. It captures complex composition, topology and function and links out to a large range of domain-specific resources that hold more detailed data, such as PDB or Reactome. We have made several significant improvements since our last update, including improving compliance to the FAIR data principles by providing complex-specific, stable identifiers that include versioning. Protein complexes are now available from 20 species for download in standards-compliant formats such as PSI-XML, MI-JSON and ComplexTAB or can be accessed via an improved REST API. A component-based JS front-end framework has been implemented to drive a new website and this has allowed the use of APIs from linked services to import and visualize information such as the 3D structure of protein complexes, its role in reactions and pathways and the co-expression of complex components in the tissues of multi-cellular organisms. A first draft of the complete complexome of Saccharomyces cerevisiae is now available to browse and download.
- MeSH
- databáze proteinů * MeSH
- konformace proteinů MeSH
- lidé MeSH
- makromolekulární látky chemie MeSH
- multiproteinové komplexy chemie metabolismus MeSH
- myši MeSH
- nukleové kyseliny chemie MeSH
- počítačová grafika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Crystallography has long been the unrivaled method that can provide the atomistic structural models of macromolecules, using either X-rays or electrons as probes. The methodology has gone through several revolutionary periods, driven by the development of new sources, detectors, and other instrumentation. Novel sources of both X-ray and electrons are constantly emerging. The increase in brightness of these sources, complemented by the advanced detection techniques, has relaxed the traditionally strict need for large, high quality, crystals. Recent reports suggest high-quality diffraction datasets from crystals as small as a few hundreds of nanometers can be routinely obtained. This has resulted in the genesis of a new field of macromolecular nanocrystal crystallography. Here we will make a brief comparative review of this growing field focusing on the use of X-rays and electrons sources.
We report a rigorous investigation into the detailed structure of nanoparticles already shown to be successful drug delivery nanocarriers. The basic structure of the drug conjugates consists of an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer bearing the anticancer drug doxorubicin (Dox) bound via a pH-sensitive hydrazone bond and a defined amount of cholesterol moieties that vary in hydrophobicity. The results show that size, anisotropy, and aggregation number N(aggr) of the nanoparticles grows with increasing cholesterol content. From ab initio calculations, we conclude that the most probable structure of HPMA copolymer-cholesterol nanoparticles is a pearl necklace structure, where ellipsoidal pearls mainly composed of cholesterol are covered by a HPMA shell; pearls are connected by bridges composed of hydrophilic HPMA copolymer chains. Using a combination of techniques, we unambiguously show that the Dox moieties are not impregnated inside a cholesterol core but are instead uniformly distributed across the whole nanoparticle, including the hydrophilic HPMA shell surface.
- MeSH
- akrylamidy chemie MeSH
- algoritmy MeSH
- anizotropie MeSH
- cholesterol MeSH
- difrakce rentgenového záření MeSH
- doxorubicin analogy a deriváty chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- makromolekulární látky chemie MeSH
- maloúhlový rozptyl MeSH
- micely MeSH
- molekulární konformace MeSH
- molekulární modely MeSH
- nanokapsle chemie MeSH
- neutronová difrakce MeSH
- protinádorová antibiotika chemie MeSH
- světlo MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
elektronický časopis
sv.
- MeSH
- makromolekulární látky MeSH
- Publikační typ
- periodika MeSH
- Konspekt
- Biologické vědy
- NLK Obory
- biologie
- biologie
This study reports the first Co2 (CO)8 -catalyzed [2+2+2] polycyclotrimerization by the transformation of internal ethynyl groups of aromatic diyne monomers. The reaction yields polycyclotrimers of polyphenylene-type with either hyperbranched or partly crosslinked architecture. The homopolycyclotrimerization of the monomers with two ethynyl groups per one molecule, namely 1,4-bis(phenylethynyl)benzene, 4,4'-bis(phenylethynyl)biphenyl, and 4-(phenylethynyl)phenylacetylene, gives partly crosslinked, insoluble polyphenylenes. The soluble, hyperbranched polyphenylenes are generated via copolycyclotrimerization of 1,4-bis(phenylethynyl)benzene with 1,2-diphenylacetylene (average number of ethynyl groups per monomer molecule < 2). This one-step polycyclotrimerization path to hyperbranched or partly crosslinked polyphenylenes is an alternative to the synthesis of these polymers by Diels-Alder transformation of substituted cyclopentadienones. All polyphenylenes prepared exhibit photoluminescence with emission maxima ranging from 381 to 495 nm. Polyphenylenes with a less compact packing of segments are microporous (specific surface area up to 159 m2 g-1 ), which is particularly important in the case of soluble polyphenylenes because they can be potentially used to prepare microporous layers.
