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, NMR 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 Protein Data Bank partnership (wwPDB; wwPDB.org). US PDB operations are the responsibility of the RCSB Protein Data Bank (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 (FDA) 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). This article is protected by copyright. All rights reserved.