RCSB Protein Data Bank (RCSB.org): delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), founding member of the Worldwide Protein Data Bank (wwPDB), is the US data center for the open-access PDB archive. As wwPDB-designated Archive Keeper, RCSB PDB is also responsible for PDB data security. Annually, RCSB PDB serves >10 000 depositors of three-dimensional (3D) biostructures working on all permanently inhabited continents. RCSB PDB delivers data from its research-focused RCSB.org web portal to many millions of PDB data consumers based in virtually every United Nations-recognized country, territory, etc. This Database Issue contribution describes upgrades to the research-focused RCSB.org web portal that created a one-stop-shop for open access to ∼200 000 experimentally-determined PDB structures of biological macromolecules alongside >1 000 000 incorporated Computed Structure Models (CSMs) predicted using artificial intelligence/machine learning methods. RCSB.org is a 'living data resource.' Every PDB structure and CSM is integrated weekly with related functional annotations from external biodata resources, providing up-to-date information for the entire corpus of 3D biostructure data freely available from RCSB.org with no usage limitations. Within RCSB.org, PDB structures and the CSMs are clearly identified as to their provenance and reliability. Both are fully searchable, and can be analyzed and visualized using the full complement of RCSB.org web portal capabilities.

Integrative illustration for coronavirus outreach.

Two illustrations integrate current knowledge about severe acute respiratory syndrome (SARS) coronaviruses and their life cycle. They have been widely used in education and outreach through free distribution as part of a coronavirus-related resource at Protein Data Bank (PDB)-101, the education portal of the RCSB PDB. Scientific sources for creation of the illustrations and examples of dissemination and response are presented.

RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), the US data center for the global PDB archive and a founding member of the Worldwide Protein Data Bank partnership, serves tens of thousands of data depositors in the Americas and Oceania and makes 3D macromolecular structure data available at no charge and without restrictions to millions of RCSB.org users around the world, including >660 000 educators, students and members of the curious public using PDB101.RCSB.org. PDB data depositors include structural biologists using macromolecular crystallography, nuclear magnetic resonance spectroscopy, 3D electron microscopy and micro-electron diffraction. PDB data consumers accessing our web portals include researchers, educators and students studying fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences. During the past 2 years, the research-focused RCSB PDB web portal (RCSB.org) has undergone a complete redesign, enabling improved searching with full Boolean operator logic and more facile access to PDB data integrated with >40 external biodata resources. New features and resources are described in detail using examples that showcase recently released structures of SARS-CoV-2 proteins and host cell proteins relevant to understanding and addressing the COVID-19 global pandemic.

Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first 6 months of the COVID-19 pandemic.

Understanding the molecular evolution of the SARS-CoV-2 virus as it continues to spread in communities around the globe is important for mitigation and future pandemic preparedness. Three-dimensional structures of SARS-CoV-2 proteins and those of other coronavirusess archived in the Protein Data Bank were used to analyze viral proteome evolution during the first 6 months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48 000 viral isolates revealed how each one of 29 viral proteins have undergone amino acid changes. Catalytic residues in active sites and binding residues in protein-protein interfaces showed modest, but significant, numbers of substitutions, highlighting the mutational robustness of the viral proteome. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi-Gaussian distribution. Detailed results are presented for potential drug discovery targets and the four structural proteins that comprise the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and protein-protein and protein-nucleic acid interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure-based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.

Safeguarding Imperiled Biodiversity and Evolutionary Processes in the Wallacea Center of Endemism.

Wallacea-the meeting point between the Asian and Australian fauna-is one of the world's largest centers of endemism. Twenty-three million years of complex geological history have given rise to a living laboratory for the study of evolution and biodiversity, highly vulnerable to anthropogenic pressures. In the present article, we review the historic and contemporary processes shaping Wallacea's biodiversity and explore ways to conserve its unique ecosystems. Although remoteness has spared many Wallacean islands from the severe overexploitation that characterizes many tropical regions, industrial-scale expansion of agriculture, mining, aquaculture and fisheries is damaging terrestrial and aquatic ecosystems, denuding endemics from communities, and threatening a long-term legacy of impoverished human populations. An impending biodiversity catastrophe demands collaborative actions to improve community-based management, minimize environmental impacts, monitor threatened species, and reduce wildlife trade. Securing a positive future for Wallacea's imperiled ecosystems requires a fundamental shift away from managing marine and terrestrial realms independently.

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

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.'

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.

The RCSB PDB "Molecule of the Month": Inspiring a Molecular View of Biology.

The Research Collaboratory for Structural Bioinformatics (RCSB) Molecule of the Month series provides a curated introduction to the 3-D biomolecular structures available in the Protein Data Bank archive and the tools that are available at the RCSB website for accessing and exploring them. A variety of educational materials, such as articles, videos, posters, hands-on activities, lesson plans, and curricula, build on this series for use in a variety of educational settings as a general introduction to key topics, such as enzyme action, protein synthesis, and viruses. The series and associated educational materials are freely available at www.rcsb.org.

RCSB PDB Mobile: iOS and Android mobile apps to provide data access and visualization to the RCSB Protein Data Bank.

SUMMARY: The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) resource provides tools for query, analysis and visualization of the 3D structures in the PDB archive. As the mobile Web is starting to surpass desktop and laptop usage, scientists and educators are beginning to integrate mobile devices into their research and teaching. In response, we have developed the RCSB PDB Mobile app for the iOS and Android mobile platforms to enable fast and convenient access to RCSB PDB data and services. Using the app, users from the general public to expert researchers can quickly search and visualize biomolecules, and add personal annotations via the RCSB PDB's integrated MyPDB service. AVAILABILITY AND IMPLEMENTATION: RCSB PDB Mobile is freely available from the Apple App Store and Google Play (http://www.rcsb.org).

Folding paper models of biostructures for outreach and education.

Molecular origami offers an offline way to explore the 3D structures of biology. Visit PDB101.rcsb.org to download free paper models of DNA, green fluorescent protein, viruses, and more.

Free-flap reconstruction of the lower limb in octogenarians - A comparative analysis of indications, management, and outcomes.

INTRODUCTION: Impaired microcirculation, along with an increase in chronic medical conditions in the geriatric cohort, may favor the development of soft-tissue defects in the lower extremity and equally impair the options for plastic-reconstructive surgery. In particular, outcome analyses in the increasing patient cohort ≥ 80 years (octogenarians) are limited. METHODS: Setting 80 years as the cutoff, we conducted an age-related outcome analysis of all patients undergoing free-flap reconstruction of the lower extremity from 2014 to 2020, comprising the American Society of Anesthesiologists (ASA) score and Charlson Comorbidity Index (CCI) as the possible outcome predicting factors. RESULTS: During the study period, a total of 424 free flaps were performed in 385 patients (∅: 54.7 years ± 16.1; range: 9-89), including 19 octogenarians. Compared with the younger patient cohort, there was a significantly higher rate of early flap revision (p = 0.023) and flap loss (p = 0.028). Furthermore, the mean length of hospital (60.6 ± 37.6 vs. 51.1 ± 37.0) and intensive care unit/intermediate care stay (6.5 ± 15.0 vs. 3.5 ± 8.5) was extended (n.s.). The ASA score presented an independent predictor for major surgical [odds ratio (OR): 1.66; p = 0.041) and medical complications (OR: 3.97; p<0.001). Neither the CCI nor the ASA served as an independent predictor for total flap loss. CONCLUSION: Free-flap reconstruction of the lower extremity in octogenarians is associated with a higher risk of flap revision and flap loss. Considering the prolonged immobilization associated with increased morbidity following limb amputation, it presents still a reasonable option to achieve limb salvage in carefully chosen patients. An adequate tool to predict the success of free-flap survival is still unavailable.

An idea to explore: How an interdisciplinary undergraduate course exploring a global health challenge in molecular detail enabled science communication and collaboration in diverse audiences.

Communication and collaboration are key science competencies that support sharing of scientific knowledge with experts and non-experts alike. On the one hand, they facilitate interdisciplinary conversations between students, educators, and researchers, while on the other they improve public awareness, enable informed choices, and impact policy decisions. Herein, we describe an interdisciplinary undergraduate course focused on using data from various bioinformatics data resources to explore the molecular underpinnings of diabetes mellitus (Types 1 and 2) and introducing students to science communication. Building on course materials and original student-generated artifacts, a series of collaborative activities engaged students, educators, researchers, healthcare professionals and community members in exploring, learning about, and discussing the molecular bases of diabetes. These collaborations generated novel educational materials and approaches to learning and presenting complex ideas about major global health challenges in formats accessible to diverse audiences.

RCSB Protein Data Bank: Efficient Searching and Simultaneous Access to One Million Computed Structure Models Alongside the PDB Structures Enabled by Architectural Advances.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) provides open access to experimentally-determined three-dimensional (3D) structures of biomolecules. The RCSB PDB RCSB.org research-focused web portal is used annually by many millions of users around the world. They access biostructure information, run complex queries utilizing various search services (e.g., full-text, structural and chemical attribute, chemical, sequence, and structure similarity searches), and visualize macromolecules in 3D, all at no charge and with no limitations on data usage. Notwithstanding more than 24,000-fold growth of the PDB over the past five decades, experimentally-determined structures are only available for a small subset of the millions of proteins of known sequence. Recently developed machine learning software tools can predict 3D structures of proteins at accuracies comparable to lower-resolution experimental methods. The RCSB PDB now provides access to ∼1,000,000 Computed Structure Models (CSMs) of proteins coming from AlphaFold DB and the ModelArchive alongside ∼200,000 experimentally-determined PDB structures. Both CSMs and PDB structures are available on RCSB.org and via well-established RCSB PDB Data, Search, and 1D-Coordinates application programming interfaces (APIs). Simultaneous delivery of PDB data and CSMs provides users with access to complementary structural information across the human proteome and those of model organisms and selected pathogens. API enhancements are backwards-compatible and programmatic users can "opt in" to access CSMs with minimal effort. Herein, we describe modifications to RCSB PDB cyberinfrastructure required to support sixfold scaling of 3D biostructure data delivery and lay the groundwork for scaling to accommodate hundreds of millions of CSMs.

PDB-101: Educational resources supporting molecular explorations through biology and medicine.

The Protein Data Bank (PDB) archive is a rich source of information in the form of atomic-level three-dimensional (3D) structures of biomolecules experimentally determined using macromolecular crystallography, nuclear magnetic resonance (NMR) spectroscopy, and electron microscopy (3DEM). Originally established in 1971 as a resource for protein crystallographers to freely exchange data, today PDB data drive research and education across scientific disciplines. In 2011, the online portal PDB-101 was launched to support teachers, students, and the general public in PDB archive exploration (pdb101.rcsb.org). Maintained by the Research Collaboratory for Structural Bioinformatics PDB, PDB-101 aims to help train the next generation of PDB users and to promote the overall importance of structural biology and protein science to nonexperts. Regularly published features include the highly popular Molecule of the Month series, 3D model activities, molecular animation videos, and educational curricula. Materials are organized into various categories (Health and Disease, Molecules of Life, Biotech and Nanotech, and Structures and Structure Determination) and searchable by keyword. A biennial health focus frames new resource creation and provides topics for annual video challenges for high school students. Web analytics document that PDB-101 materials relating to fundamental topics (e.g., hemoglobin, catalase) are highly accessed year-on-year. In addition, PDB-101 materials created in response to topical health matters (e.g., Zika, measles, coronavirus) are well received. PDB-101 shows how learning about the diverse shapes and functions of PDB structures promotes understanding of all aspects of biology, from the central dogma of biology to health and disease to biological energy.

Protein Data Bank: A Comprehensive Review of 3D Structure Holdings and Worldwide Utilization by Researchers, Educators, and Students.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), funded by the United States National Science Foundation, National Institutes of Health, and Department of Energy, supports structural biologists and Protein Data Bank (PDB) data users around the world. The RCSB PDB, a founding member of the Worldwide Protein Data Bank (wwPDB) partnership, serves as the US data center for the global PDB archive housing experimentally-determined three-dimensional (3D) structure data for biological macromolecules. As the wwPDB-designated Archive Keeper, RCSB PDB is also responsible for the security of PDB data and weekly update of the archive. RCSB PDB serves tens of thousands of data depositors (using macromolecular crystallography, nuclear magnetic resonance spectroscopy, electron microscopy, and micro-electron diffraction) annually working on all permanently inhabited continents. RCSB PDB makes PDB data available from its research-focused web portal at no charge and without usage restrictions to many millions of PDB data consumers around the globe. It also provides educators, students, and the general public with an introduction to the PDB and related training materials through its outreach and education-focused web portal. This review article describes growth of the PDB, examines evolution of experimental methods for structure determination viewed through the lens of the PDB archive, and provides a detailed accounting of PDB archival holdings and their utilization by researchers, educators, and students worldwide.

RCSB Protein Data Bank: Celebrating 50 years of the PDB with new tools for understanding and visualizing biological macromolecules in 3D.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), funded by the US National Science Foundation, National Institutes of Health, and Department of Energy, has served structural biologists and Protein Data Bank (PDB) data consumers worldwide since 1999. RCSB PDB, a founding member of the Worldwide Protein Data Bank (wwPDB) partnership, is the US data center for the global PDB archive housing biomolecular structure data. RCSB PDB is also responsible for the security of PDB data, as the wwPDB-designated Archive Keeper. Annually, RCSB PDB serves tens of thousands of three-dimensional (3D) macromolecular structure data depositors (using macromolecular crystallography, nuclear magnetic resonance spectroscopy, electron microscopy, and micro-electron diffraction) from all inhabited continents. RCSB PDB makes PDB data available from its research-focused RCSB.org web portal at no charge and without usage restrictions to millions of PDB data consumers working in every nation and territory worldwide. In addition, RCSB PDB operates an outreach and education PDB101.RCSB.org web portal that was used by more than 800,000 educators, students, and members of the public during calendar year 2020. This invited Tools Issue contribution describes (i) how the archive is growing and evolving as new experimental methods generate ever larger and more complex biomolecular structures; (ii) the importance of data standards and data remediation in effective management of the archive and facile integration with more than 50 external data resources; and (iii) new tools and features for 3D structure analysis and visualization made available during the past year via the RCSB.org web portal.

Effectiveness of 20 years of conservation investments in protecting orangutans.

Conservation strategies are rarely systematically evaluated, which reduces transparency, hinders the cost-effective deployment of resources, and hides what works best in different contexts. Using data on the iconic and critically endangered orangutan (Pongo spp.), we developed a novel spatiotemporal framework for evaluating conservation investments. We show that around USD 1 billion was invested between 2000 and 2019 into orangutan conservation by governments, nongovernmental organizations, companies, and communities. Broken down by allocation to different conservation strategies, we find that habitat protection, patrolling, and public outreach had the greatest return on investment for maintaining orangutan populations. Given the variability in threats, land-use opportunity costs, and baseline remunerations in different regions, there were differential benefits per dollar invested across conservation activities and regions. We show that although challenging from a data and analysis perspective, it is possible to fully understand the relationships between conservation investments and outcomes and the external factors that influence these outcomes. Such analyses can provide improved guidance toward a more effective biodiversity conservation. Insights into the spatiotemporal interplays between the costs and benefits driving effectiveness can inform decisions about the most suitable orangutan conservation strategies for halting population declines. Although our study focuses on the three extant orangutan species of Sumatra and Borneo, our findings have broad application for evidence-based conservation science and practice worldwide.

RCSB Protein Data bank: Tools for visualizing and understanding biological macromolecules in 3D.

Now in its 52nd year of continuous operations, the Protein Data Bank (PDB) is the premiere open-access global archive housing three-dimensional (3D) biomolecular structure data. It is jointly managed by the Worldwide Protein Data Bank (wwPDB) partnership. The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) is funded by the National Science Foundation, National Institutes of Health, and US Department of Energy and serves as the US data center for the wwPDB. RCSB PDB is also responsible for the security of PDB data in its role as wwPDB-designated Archive Keeper. Every year, RCSB PDB serves tens of thousands of depositors of 3D macromolecular structure data (coming from macromolecular crystallography, nuclear magnetic resonance spectroscopy, electron microscopy, and micro-electron diffraction). The RCSB PDB research-focused web portal (RCSB.org) makes PDB data available at no charge and without usage restrictions to many millions of PDB data consumers around the world. The RCSB PDB training, outreach, and education web portal (PDB101.RCSB.org) serves nearly 700 K educators, students, and members of the public worldwide. This invited Tools Issue contribution describes how RCSB PDB (i) is organized; (ii) works with wwPDB partners to process new depositions; (iii) serves as the wwPDB-designated Archive Keeper; (iv) enables exploration and 3D visualization of PDB data via RCSB.org; and (v) supports training, outreach, and education via PDB101.RCSB.org. New tools and features at RCSB.org are presented using examples drawn from high-resolution structural studies of proteins relevant to treatment of human cancers by targeting immune checkpoints.

Molecular storytelling for online structural biology outreach and education.

Knowledge about the structure and function of biomolecules continues to grow exponentially, enabling us to "see" structural snapshots of biomolecular interactions and functional assemblies. At PDB-101, the educational portal of the RCSB Protein Data Bank, we have taken a storytelling approach to make this body of knowledge accessible and comprehensible to a wide community of students, educators, and the general public. For over 20 years, the Molecule of the Month series has utilized a traditional illustrated storytelling approach that is regularly adapted for classroom instruction. Similar visual and interactive storytelling approaches are used to present topical subjects at PDB-101 and full curricular materials and case studies for building a detailed narrative around topics of particular interest. This emphasis on storytelling led to the Video Challenge for High School students, now in its 8th year. In this Article, we will present some of the lessons we have learned for teaching and communicating structural biology using the PDB archive of biomolecular structures.

Validity of Plate Diagrams for Estimation of Energy and Protein Intake of Nursing Home Residents Receiving Texture-Modified Diet: An enable Study.

OBJECTIVES: Nursing home (NH) residents receiving texture-modified diet (TMD) are at risk of inadequate nutritional intake and subsequent malnutrition. It is essential to monitor dietary intake to take corrective actions, if necessary. Plate diagrams (PDs) are widely used to assess dietary intake in institutions but little is known about their validity for TMD. DESIGN: Dietary intake at main meals was assessed by nursing personnel via PDs and scientific personnel via weighing records (WRs). SETTING AND PARTICIPANTS: 17 NH residents receiving TMD on a regular basis. METHODS: Intake from main meals (breakfast, lunch, and dinner) at 48 days was estimated by nursing personnel in quarters of the offered amount [nothing, », ½, ¾, all, all plus second helping (54), or I do not know] and by scientific personnel via WRs. PD estimation was multiplied by the energy and protein content of the offered meal determined by WR and compared to WR intake results. Sums of daily PD quarters were drawn against WR intake results. RESULTS: Energy and protein intake from main meals separately and in total per day were highly correlated (r > 0.854, all P < .001). Paired statistics showed no significant differences between assessment methods (P > .05). Mean differences [±standard deviation (SD)] between PD and WR were 13.9 (±68.6) kcal, which is 1.7% of the mean weighed caloric intake, and 0.2 (±3.3) g protein, which is 0.5% of the mean weighed protein intake per day. Daily energy and protein intake from main meals determined by WR varies widely within each category of summed daily intake quarters; for example, a sum of PD quarters of 12 (ie, "all eaten at all meals") showed corresponding WR intake levels from 394.6 to 1368.9 kcal and 16.3 to 63.0 g protein. CONCLUSIONS AND IMPLICATIONS: Energy and protein intake from TMD estimated by PD corresponds very well to WR-determined intake, if the energy and protein content of the offered meals is known.