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. 2020 Jan;29(1):52-65.
doi: 10.1002/pro.3730. Epub 2019 Nov 29.

RCSB Protein Data Bank: Enabling biomedical research and drug discovery

David S Goodsell  1   2   3 , Christine Zardecki  1   2 , Luigi Di Costanzo  1   2 , Jose M Duarte  4 , Brian P Hudson  1   2 , Irina Persikova  1   2 , Joan Segura  4 , Chenghua Shao  1   2 , Maria Voigt  1   2 , John D Westbrook  1   2 , Jasmine Y Young  1   2 , Stephen K Burley  1   2   4   5
Affiliations

RCSB Protein Data Bank: Enabling biomedical research and drug discovery

David S Goodsell et al. Protein Sci. 2020 Jan.

Abstract

Analyses of publicly available structural data reveal interesting insights into the impact of the three-dimensional (3D) structures of protein targets important for discovery of new drugs (e.g., G-protein-coupled receptors, voltage-gated ion channels, ligand-gated ion channels, transporters, and E3 ubiquitin ligases). The Protein Data Bank (PDB) archive currently holds > 155,000 atomic-level 3D structures of biomolecules experimentally determined using crystallography, nuclear magnetic resonance spectroscopy, and electron microscopy. The PDB was established in 1971 as the first open-access, digital-data resource in biology, and is now managed by the Worldwide PDB partnership (wwPDB; wwPDB.org). US PDB operations are the responsibility of the Research Collaboratory for Structural Bioinformatics PDB (RCSB PDB). The RCSB PDB serves millions of RCSB.org users worldwide by delivering PDB data integrated with ∼40 external biodata resources, providing rich structural views of fundamental biology, biomedicine, and energy sciences. Recently published work showed that the PDB archival holdings facilitated discovery of ∼90% of the 210 new drugs approved by the US Food and Drug Administration 2010-2016. We review user-driven development of RCSB PDB services, examine growth of the PDB archive in terms of size and complexity, and present examples and opportunities for structure-guided drug discovery for challenging targets (e.g., integral membrane proteins).

Keywords: GPCR; Protein Data Bank; integral membrane proteins; ion channel; protein structure and function; structural biology; structure-guided drug discovery; transporter; ubiquitin ligase.

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Figures

Figure 1
Figure 1
Growth of PDB archive, 2000–2018. (a) Total number of structures publicly available each year by experimental method and (b) new structures released annually by experimental method, shown using logarithmic scale
Figure 2
Figure 2
Growth in the complexity of PDB archival holdings 2000–2018. (a) Cumulative number of unique ligands maintained in the Chemical Component Dictionary each year. In 2018, 2,498 new entries were added. (b) Average molecular weight (solid purple line) and average number of polymer chains (solid orange line) of structures released each year. (c) Growth in available EM structure data, shown by annual accumulation of number of chains and molecular weight
Figure 3
Figure 3
Ribbon drawings of exemplar structures from each of the four classes of membrane‐bound proteins of pharmacologic interest, viewed parallel to the lipid bilayer (shaded grey rectangle). (a) GPCR (PDB 5vai)36: GLP1‐R (glucagon‐like peptide‐1 receptor, active conformation in green) bound to GLP1 (red) and heterotrimeric G‐protein (blue, yellow, and magenta). (b) VGIC (PDB 6j8i)106: Nav1.7 (green), beta1 and beta2 (blue), bound to inhibitor tetrodotoxin (yellow). Voltage‐sensing helices are shown in red. (c) LGIC (PDB 5uow)72: NMDA receptor (blue, green, and red) bound to channel blocker MK‐801 (magenta). An antibody Fab (grey) was used in the structure determination. (d) Transporter (PDB 6o2p)85: CFTR (cystic fibrosis transmembrane conductance regulator (blue) bound to ivacaftor (yellow), which interacts with a long transmembrane helix involved in gating (red)
Figure 4
Figure 4
(a) Early structures of the components of the ubiquitin ligase system (E1,107 E2,108 and E3109, 110). Image from PDB‐101's Molecule of the Month.21 (b) Ribbon structure of the PROTAC (proteolysis targeting chimera) degrader MZ1 (yellow) linking cancer target Brd4 (red) to a ubiquitin ligase complex of pVHL:ElonginC:ElonginB (blue and green) from PDB 6bn7103
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References

    1. Protein Data Bank . Protein Data Bank. Nature New Biol. 1971;233:223. - PubMed
    1. Protein Data Bank . Cold spring harbor symposia on quantitative biology. Vol 36 New York, NY: Cold Spring Laboratory Press, 1972.
    1. Sullivan KP, Brennan‐Tonetta P, Marxen LJ (2017) Economic impacts of the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank. doi: 10.2210/rcsb_pdb/pdb-econ-imp-2017. - DOI
    1. wwPDB consortium . Protein Data Bank: The single global archive for 3D macromolecular structure data. Nucleic Acids Res. 2019;47:D520–D528. - PMC - PubMed
    1. Berman HM, Westbrook J, Feng Z, et al. The Protein Data Bank. Nucleic Acids Res. 2000;28:235–242. - PMC - PubMed

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