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1. Updated resources for exploring experimentally-determined PDB structures and Computed Structure Models at the RCSB Protein Data Bank

   https://doi.org/10.1093/nar/gkae1091  

   Burley, Stephen K.; Bhatt, Rusham; Bhikadiya, Charmi; Bi, Chunxiao; Biester, Alison; Biswas, Pratyoy; Bittrich, Sebastian; Blaumann, Santiago; Brown, Ronald; Chao, Henry; et al (November 2024, Nucleic Acids Research)

   Abstract The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, RCSB.org), the US Worldwide Protein Data Bank (wwPDB, wwPDB.org) data center for the global PDB archive, provides access to the PDB data via its RCSB.org research-focused web portal. We report substantial additions to the tools and visualization features available at RCSB.org, which now delivers more than 227000 experimentally determined atomic-level three-dimensional (3D) biostructures stored in the global PDB archive alongside more than 1 million Computed Structure Models (CSMs) of proteins (including models for human, model organisms, select human pathogens, crop plants and organisms important for addressing climate change). In addition to providing support for 3D structure motif searches with user-provided coordinates, new features highlighted herein include query results organized by redundancy-reduced Groups and summary pages that facilitate exploration of groups of similar proteins. Newly released programmatic tools are also described, as are enhanced training opportunities. 

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2. 3D-equivariant graph neural networks for protein model quality assessment

   https://doi.org/10.1093/bioinformatics/btad030  

   Chen, Chen; Chen, Xiao; Morehead, Alex; Wu, Tianqi; Cheng, Jianlin; Cowen, ed., Lenore (January 2023, Bioinformatics)

   Abstract MotivationQuality assessment (QA) of predicted protein tertiary structure models plays an important role in ranking and using them. With the recent development of deep learning end-to-end protein structure prediction techniques for generating highly confident tertiary structures for most proteins, it is important to explore corresponding QA strategies to evaluate and select the structural models predicted by them since these models have better quality and different properties than the models predicted by traditional tertiary structure prediction methods. ResultsWe develop EnQA, a novel graph-based 3D-equivariant neural network method that is equivariant to rotation and translation of 3D objects to estimate the accuracy of protein structural models by leveraging the structural features acquired from the state-of-the-art tertiary structure prediction method—AlphaFold2. We train and test the method on both traditional model datasets (e.g. the datasets of the Critical Assessment of Techniques for Protein Structure Prediction) and a new dataset of high-quality structural models predicted only by AlphaFold2 for the proteins whose experimental structures were released recently. Our approach achieves state-of-the-art performance on protein structural models predicted by both traditional protein structure prediction methods and the latest end-to-end deep learning method—AlphaFold2. It performs even better than the model QA scores provided by AlphaFold2 itself. The results illustrate that the 3D-equivariant graph neural network is a promising approach to the evaluation of protein structural models. Integrating AlphaFold2 features with other complementary sequence and structural features is important for improving protein model QA. Availability and implementationThe source code is available at https://github.com/BioinfoMachineLearning/EnQA. Supplementary informationSupplementary data are available at Bioinformatics online. 

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3. 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

   https://doi.org/10.1093/nar/gkaa1038  

   Burley, Stephen K; Bhikadiya, Charmi; Bi, Chunxiao; Bittrich, Sebastian; Chen, Li; Crichlow, Gregg V; Christie, Cole H; Dalenberg, Kenneth; Di Costanzo, Luigi; Duarte, Jose M; et al (November 2020, Nucleic Acids Research)

   Abstract 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. 

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4. Functional annotation of haloacid dehalogenase superfamily structural genomics proteins

   https://doi.org/10.1042/BCJ20230057  

   Pathira Kankanamge, Lakindu S.; Ruffner, Lydia A.; Touch, Mong Mary; Pina, Manuel; Beuning, Penny J.; Ondrechen, Mary Jo (October 2023, Biochemical Journal)

   Haloacid dehalogenases (HAD) are members of a large superfamily that includes many Structural Genomics proteins with poorly characterized functionality. This superfamily consists of multiple types of enzymes that can act as sugar phosphatases, haloacid dehalogenases, phosphonoacetaldehyde hydrolases, ATPases, or phosphate monoesterases. Here, we report on predicted functional annotations and experimental testing by direct biochemical assay for Structural Genomics proteins from the HAD superfamily. To characterize the functions of HAD superfamily members, nine representative HAD proteins and 21 structural genomics proteins are analyzed. Using techniques based on computed chemical and electrostatic properties of individual amino acids, the functions of five structural genomics proteins from the HAD superfamily are predicted and validated by biochemical assays. A dehalogenase-like hydrolase, RSc1362 (Uniprot Q8XZN3, PDB 3UMB) is predicted to be a dehalogenase and dehalogenase activity is confirmed experimentally. Four proteins predicted to be sugar phosphatases are characterized as follows: a sugar phosphatase from Thermophilus volcanium (Uniprot Q978Y6) with trehalose-6-phosphate phosphatase and fructose-6-phosphate phosphatase activity; haloacid dehalogenase-like hydrolase from Bacteroides thetaiotaomicron (Uniprot Q8A2F3; PDB 3NIW) with fructose-6-phosphate phosphatase and sucrose-6-phosphate phosphatase activity; putative phosphatase from Eubacterium rectale (Uniprot D0VWU2; PDB 3DAO) as a sucrose-6-phosphate phosphatase; and hypothetical protein from Geobacillus kaustophilus (Uniprot Q5L139; PDB 2PQ0) as a fructose-6-phosphate phosphatase. Most of these sugar phosphatases showed some substrate promiscuity. 

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5. Electron microscopy holdings of the Protein Data Bank: the impact of the resolution revolution, new validation tools, and implications for the future

   https://doi.org/10.1007/s12551-022-01013-w  

   Burley, Stephen K.; Berman, Helen M.; Chiu, Wah; Dai, Wei; Flatt, Justin W.; Hudson, Brian P.; Kaelber, Jason T.; Khare, Sagar D.; Kulczyk, Arkadiusz W.; Lawson, Catherine L.; et al (December 2022, Biophysical Reviews)

   Abstract As a discipline, structural biology has been transformed by the three-dimensional electron microscopy (3DEM) “Resolution Revolution” made possible by convergence of robust cryo-preservation of vitrified biological materials, sample handling systems, and measurement stages operating a liquid nitrogen temperature, improvements in electron optics that preserve phase information at the atomic level, direct electron detectors (DEDs), high-speed computing with graphics processing units, and rapid advances in data acquisition and processing software. 3DEM structure information (atomic coordinates and related metadata) are archived in the open-access Protein Data Bank (PDB), which currently holds more than 11,000 3DEM structures of proteins and nucleic acids, and their complexes with one another and small-molecule ligands (~ 6% of the archive). Underlying experimental data (3DEM density maps and related metadata) are stored in the Electron Microscopy Data Bank (EMDB), which currently holds more than 21,000 3DEM density maps. After describing the history of the PDB and the Worldwide Protein Data Bank (wwPDB) partnership, which jointly manages both the PDB and EMDB archives, this review examines the origins of the resolution revolution and analyzes its impact on structural biology viewed through the lens of PDB holdings. Six areas of focus exemplifying the impact of 3DEM across the biosciences are discussed in detail (icosahedral viruses, ribosomes, integral membrane proteins, SARS-CoV-2 spike proteins, cryogenic electron tomography, and integrative structure determination combining 3DEM with complementary biophysical measurement techniques), followed by a review of 3DEM structure validation by the wwPDB that underscores the importance of community engagement. 

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