Exploring Validation of PDB Experimental Structures and Computed Structure Models at RCSB.org

In addition to providing open access to >220,000 experimentally-determined three-dimensional (3D) structures of biological macromolecules stored in the Protein Data Bank archive (PDB), the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) research-focused web portal (RCSB.org) serves >1 million Computed Structure Models (CSMs, predicted protein structures) generated using AlphaFold2 (from AlphaFold DB) or RoseTTAFold2/AlphaFold2 (from ModelArchive). All PDB structures and CSMs made freely available from RCSB.org are integrated weekly with related functional annotations from trusted external resources, providing up-to-date information for each 3D biostructure. Both PDB structures and CSMs can be searched, analyzed, and visualized with an extensive array of user-friendly RCSB PDB online resources. Provenance and reliability of PDB data and CSMs are clearly identified at RCSB.org. For PDB structures, users can access primary PDB structure quality metrics, including those summarized in the validation slider graphic and explore how structure quality varies within a PDB structure (using Mol* 3D visualization) and across the entire archive. These RCSB.org tools can help identify experimentally-determined structure(s) that are most appropriate for developing testable hypotheses and supporting basic and applied research across the biological and biomedical sciences. CSMs offer great alternatives and/or starting models for data analysis and hypothesis generation when a relevant experimentally-determined structure is not available at the PDB. Simultaneous delivery of PDB data and CSMs provides access to 3D structure information across the proteomes of H. sapiens, various model organisms (i.e., mouse, worm, fly, etc.), select human pathogens, and organisms important in the fight against climate change (e.g., A. thaliana, S. divinum). CSMs do, however, have their limitations. Typically, they are comparable in accuracy to lower-resolution experimental structures and should not be relied on when a corresponding PDB structure(s) is available. Similar to the validation slider for experimentally- determined structures archived in the PDB, all CSMs delivered via RCSB.org report global and local prediction confidence as pLDDT scores. CSM prediction confidence scoring is also displayed in 3D using Mol*. RCSB PDB Core Operations are funded by the National Science Foundation (DBI-2321666), the US Department of Energy (DE- SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.