Luigi Di Costanzo

The RCSB protein data bank: integrative view of protein, gene and 3D structural information

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, http://rcsb.org), the US data center for the global PDB archive, makes PDB data freely available to all users, from structural biologists to computational biologists and beyond. New tools and resources have been added to the RCSB PDB web portal in support of a ‘Structural View of Biology.’ Recent developments have improved the User experience, including the high-speed NGL Viewer that provides 3D molecular visualization in any web browser, improved support for data file download and enhanced organization of website pages for query, reporting and individual structure exploration. Structure validation information is now visible for all archival entries. PDB data have been integrated with external biological resources, including chromosomal position within the human genome; protein modifications; and metabolic pathways. PDB-101 educational materials have been reorganized into a searchable website and expanded to include new features such as the Geis Digital Archive.

Trendspotting in the Protein Data Bank.

The Protein Data Bank (PDB) was established in 1971 as a repository for the three dimensional structures of biological macromolecules. Since then, more than 85 000 biological macromolecule structures have been determined and made available in the PDB archive. Through analysis of the corpus of data, it is possible to identify trends that can be used to inform us abou the future of structural biology and to plan the best ways to improve the management of the ever‐growing amount of PDB data.

Structure of anticancer ruthenium half-sandwich complex bound to glycogen synthase kinase 3β

The 3.15-Å-resolution crystal structure of the R enantiomer of the highly bioactive and antiproliferative half-sandwich ruthenium complex DW12 bound to the ATP binding site of glycogen synthase kinase 3β (GSK-3β) is reported and the binding is compared with the GSK-3β binding of staurosporine and other organic inhibitors. The structure reveals a close packing of the organometallic inhibitor in the ATP binding site of GSK-3β via an induced-fit mechanism. The molecular structure of (R)-DW12 with the CO ligand oriented perpendicular to the pyridocarbazole heterocycle allows the complex to stretch the whole distance sandwiched between the faces of the N- and C-terminal lobes and to interact tightly with the flexible glycine-rich loop, which is uncommon for the interaction of GSK-3β with organic inhibitors.

OneDep: Unified wwPDB System for Deposition, Biocuration, and Validation of Macromolecular Structures in the PDB Archive

OneDep, a unified system for deposition, biocuration, and validation of experimentally determined structures of biological macromolecules to the PDB archive, has been developed as a global collaboration by the worldwide PDB (wwPDB) partners. This new system was designed to ensure that the wwPDB could meet the evolving archiving requirements of the scientific community over the coming decades. OneDep unifies deposition, biocuration, and validation pipelines across all wwPDB, EMDB, and BMRB deposition sites with improved focus on data quality and completeness in these archives, while supporting growth in the number of depositions and increases in their average size and complexity. In this paper, we describe the design, functional operation, and supporting infrastructure of the OneDep system, and provide initial performance assessments.

Small molecule annotation for the Protein Data Bank

The Protein Data Bank (PDB) is the single global repository for three-dimensional structures of biological macromolecules and their complexes, and its more than 100 000 structures contain more than 20 000 distinct ligands or small molecules bound to proteins and nucleic acids. Information about these small molecules and their interactions with proteins and nucleic acids is crucial for our understanding of biochemical processes and vital for structure-based drug design. Small molecules present in a deposited structure may be attached to a polymer or may occur as a separate, non-covalently linked ligand. During curation of a newly deposited structure by wwPDB annotation staff, each molecule is cross-referenced to the PDB Chemical Component Dictionary (CCD). If the molecule is new to the PDB, a dictionary description is created for it. The information about all small molecule components found in the PDB is distributed via the ftp archive as an external reference file. Small molecule annotation in the PDB also includes information about ligand-binding sites and about covalent and other linkages between ligands and macromolecules. During the remediation of the peptide-like antibiotics and inhibitors present in the PDB archive in 2011, it became clear that additional annotation was required for consistent representation of these molecules, which are quite often composed of several sequential subcomponents including modified amino acids and other chemical groups. The connectivity information of the modified amino acids is necessary for correct representation of these biologically interesting molecules. The combined information is made available via a new resource called the Biologically Interesting molecules Reference Dictionary, which is complementary to the CCD and is now routinely used for annotation of peptide-like antibiotics and inhibitors.

Analysis of impact metrics for the Protein Data Bank

Since 1971, the Protein Data Bank (PDB) archive has served as the single, global repository for open access to atomic-level data for biological macromolecules. The archive currently holds >140,000 structures (>1 billion atoms). These structures are the molecules of life found in all organisms. Knowing the 3D structure of a biological macromolecule is essential for understanding the molecule’s function, providing insights in health and disease, food and energy production, and other topics of concern to prosperity and sustainability. PDB data are freely and publicly available, without restrictions on usage. Through bibliometric and usage studies, we sought to determine the impact of the PDB across disciplines and demographics. Our analysis shows that even though research areas such as molecular biology and biochemistry account for the most usage, other fields are increasingly using PDB resources. PDB usage is seen across 150 disciplines in applied sciences, humanities, and social sciences. Data are also re-used and integrated with >400 resources. Our study identifies trends in PDB usage and documents its utility across research disciplines.

Worldwide Protein Data Bank biocuration supporting open access to high-quality 3D structural biology data

Abstract The Protein Data Bank (PDB) is the single global repository for experimentally determined 3D structures of biological macromolecules and their complexes with ligands. The worldwide PDB (wwPDB) is the international collaboration that manages the PDB archive according to the FAIR principles: Findability, Accessibility, Interoperability and Reusability. The wwPDB recently developed OneDep, a unified tool for deposition, validation and biocuration of structures of biological macromolecules. All data deposited to the PDB undergo critical review by wwPDB Biocurators. This article outlines the importance of biocuration for structural biology data deposited to the PDB and describes wwPDB biocuration processes and the role of expert Biocurators in sustaining a high-quality archive. Structural data submitted to the PDB are examined for self-consistency, standardized using controlled vocabularies, cross-referenced with other biological data resources and validated for scientific/technical accuracy. We illustrate how biocuration is integral to PDB data archiving, as it facilitates accurate, consistent and comprehensive representation of biological structure data, allowing efficient and effective usage by research scientists, educators, students and the curious public worldwide. Database URL: https://www.wwpdb.org/

RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy

Abstract The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, rcsb.org), the US data center for the global PDB archive, serves thousands of Data Depositors in the Americas and Oceania and makes 3D macromolecular structure data available at no charge and without usage restrictions to more than 1 million rcsb.org Users worldwide and 600 000 pdb101.rcsb.org education-focused Users around the globe. PDB Data Depositors include structural biologists using macromolecular crystallography, nuclear magnetic resonance spectroscopy and 3D electron microscopy. PDB Data Consumers include researchers, educators and students studying Fundamental Biology, Biomedicine, Biotechnology and Energy. Recent reorganization of RCSB PDB activities into four integrated, interdependent services is described in detail, together with tools and resources added over the past 2 years to RCSB PDB web portals in support of a ‘Structural View of Biology.’

Protein Data Bank: the single global archive for 3D macromolecular structure data

Abstract The Protein Data Bank (PDB) is the single global archive of experimentally determined three-dimensional (3D) structure data of biological macromolecules. Since 2003, the PDB has been managed by the Worldwide Protein Data Bank (wwPDB; wwpdb.org), an international consortium that collaboratively oversees deposition, validation, biocuration, and open access dissemination of 3D macromolecular structure data. The PDB Core Archive houses 3D atomic coordinates of more than 144 000 structural models of proteins, DNA/RNA, and their complexes with metals and small molecules and related experimental data and metadata. Structure and experimental data/metadata are also stored in the PDB Core Archive using the readily extensible wwPDB PDBx/mmCIF master data format, which will continue to evolve as data/metadata from new experimental techniques and structure determination methods are incorporated by the wwPDB. Impacts of the recently developed universal wwPDB OneDep deposition/validation/biocuration system and various methods-specific wwPDB Validation Task Forces on improving the quality of structures and data housed in the PDB Core Archive are described together with current challenges and future plans.

Amino acid modifications for conformationally constraining naturally occurring and engineered peptide backbones: Insights from the Protein Data Bank

Extensive efforts invested in understanding the rules of protein folding are now being applied, with good effect, in de novo design of proteins/peptides. For proteins containing standard α‐amino acids alone, knowledge derived from experimentally determined three‐dimensional (3D) structures of proteins and biologically active peptides are available from the Protein Data Bank (PDB), and the Cambridge Structural Database (CSD). These help predict and design protein structures, with reasonable confidence. However, our knowledge of 3D structures of biomolecules containing backbone modified amino acids is still evolving. A major challenge in de novo protein/peptide design concerns the engineering of conformationally constrained molecules with specific structural elements and chemical groups appropriately positioned for biological activity. This review explores four classes of amino acid modifications that constrain protein/peptide backbone structure. Systematic analysis of peptidic molecule structures (eg, bioactive peptides, inhibitors, antibiotics, and designed molecules), containing these backbone‐modified amino acids, found in the PDB and CSD are discussed. The review aims to provide structure–function insights that will guide future design of proteins/peptides.