RCSB Protein Data Bank resources for structure-facilitated design of mRNA vaccines for existing and emerging viral pathogens

Goodsell, David S.; Burley, S.K.

doi:10.1016/j.str.2021.10.008

Cited by 12 publications

(9 citation statements)

References 92 publications

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“…A recently published RCSB PDB article described PDB‐related resources related to structure‐facilitated messenger RNA vaccine design. 140 Similarly, new PDB‐101 resources are being used to explain what we know about the structural biology and vaccinology of poxviruses in response to concerning reports of outbreaks of monkeypox in non‐endemic areas (accessible by searching PDB101.RCSB.org with the keyword “poxviruses”). PDB‐101 features on Ebola Virus published in 2014, including a MotM article, 141 an award‐winning Ebola Virus Illustration, and an Ebola Virus Protein Video, are likely to attract renewed interest in the wake of recent outbreaks in Uganda.…”

Section: Resultsmentioning

confidence: 99%

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

Burley

Bhikadiya

et al. 2022

Protein Science

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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 (http://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 (http://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 http://RCSB.org; and (v) supports training, outreach, and education via http://PDB101.RCSB.org. New tools and features at http://RCSB.org are presented using examples drawn from high‐resolution structural studies of proteins relevant to treatment of human cancers by targeting immune checkpoints.

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Section: Resultsmentioning

confidence: 99%

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

Burley

Bhikadiya

et al. 2022

Protein Science

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“…On the public health front, 3DEM structures of icosahedral viruses are informing our understanding of important viral pathogens. For example, atomic coordinates of Dengue, West Nile, and Zika flaviviruses have enabled mapping sites of glycosylation, amino-acid sequence variation, and neutralizing antibody binding and vaccine design (Goodsell and Burley 2022;Hasan et al 2018).…”

Section: Area Of Focus No 1: 60-fold Symmetric Icosahedral Virusesmentioning

confidence: 99%

“…4). Some of these data and earlier PDB structures of SARS-CoV spike proteins have informed design of vaccines (Goodsell and Burley 2022) and development of monoclonal antibodies to combat the COVID-19 pandemic (Gilliland et al 2012;Chiu and Gilliland 2016). Equally impressive is the fact that previously encountered technical limitations of cryo-EM methods with respect to size (e.g., smaller < 200 kDa macromolecules) and complexity (e.g., distinct molecular entities ≥ 10) have been largely overcome.…”

Section: Introductionmentioning

confidence: 98%

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

et al. 2022

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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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“…Aiming at the above problems, we propose to construct a simulation dataset to construct a simulated cryo-EM single-particle dataset by adding the real noise of cryo-EM to the projection image [16]. When obtaining the projection map, we first selected three protein macromolecules with PDB structures from the electron microscopy database (EMDB) [17], corresponding to IDs of 3j7a, 5u6o and 5irx, and their specific parameters are shown in Table 1. Then, Use the XMIPP [18] software processing package to simulate the effects of a real microscope.…”

Section: Construct Simulation Datasetmentioning

confidence: 99%

SimCryoCluster: A Semantic Similarity Clustering Method of Cryo-EM Images by Adopting Contrastive Learning

Tang

Wang

Ouyang

et al. 2022

Preprint

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Background: Cryo-electron microscopy (Cryo-EM) plays an increasingly important role in the determination of the three-dimensional (3D) structure of macromolecules. In order to achieve 3D reconstruction results close to atomic resolution, 2D single-particle image classification is not only conducive to single-particle selection, but also a key step that affects 3D reconstruction. The main task is to cluster and align 2D single-grain images into non-heterogeneous groups to obtain sharper single-grain images by averaging calculations. The main difficulties are that the cryo-EM single-particle image has a low signal-to-noise ratio (SNR), cannot manually label the data, and the projection direction is random and the distribution is unknown. Therefore, in the low SNR scenario, how to obtain the characteristic information of the effective particles, improve the clustering accuracy, and thus improve the reconstruction accuracy, is a key problem in the 2D image analysis of single particles of cryo-EM.Results: Aiming at the above problems, we propose a learnable deep clustering method and a fast alignment weighted averaging method based on frequency domain space to effectively improve the class averaging results and improve the reconstruction accuracy. In particular, it is very prominent in the feature extraction and dimensionality reduction module. Compared with the classification method based on Bayesian and great likelihood, a large amount of single particle data is required to estimate the relative angle orientation of macromolecular single particles in the 3D structure, and we propose that the clustering method shows good results.Conclusions: SimcryoCluster can use the contrastive learning method to perform well in the unlabeled high-noise cryo-EM single particle image classification task, making it an important tool for cryo-EM protein structure determination.

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RCSB Protein Data Bank resources for structure-facilitated design of mRNA vaccines for existing and emerging viral pathogens

Cited by 12 publications

References 92 publications

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

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

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

SimCryoCluster: A Semantic Similarity Clustering Method of Cryo-EM Images by Adopting Contrastive Learning

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