RCSB Protein Data Bank: Enabling biomedical research and drug discovery

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; ). US PDB operations are the responsibility of the Research Collaboratory for Structural Bioinformatics PDB (RCSB PDB). The RCSB PDB serves millions of users worldwide by delivering PDB data integrated with similar to 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 similar to 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).