RCSB Protein Data Bank: Efficient Searching and Simultaneous Access to One Million Computed Structure Models Alongside the PDB Structures Enabled by Architectural Advances

Abstract

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) provides open access to experimentally-determined three-dimensional (3D) structures of biomolecules. The RCSB PDB RCSB.org research-focused web portal is used annually by many millions of users around the world. They access biostructure information, run complex queries utilizing various search services (e.g., full-text, structural and chemical attribute, chemical, sequence, and structure similarity searches), and visualize macromolecules in 3D, all at no charge and with no limitations on data usage. Notwithstanding more than 24,000-fold growth of the PDB over the past five decades, experimentally-determined structures are only available for a small subset of the millions of proteins of known sequence. Recently developed machine learning software tools can predict 3D structures of proteins at accuracies comparable to lower-resolution experimental methods. The RCSB PDB now provides access to ∼1,000,000 Computed Structure Models (CSMs) of proteins coming from AlphaFold DB and the ModelArchive alongside ∼200,000 experimentally-determined PDB structures. Both CSMs and PDB structures are available on RCSB.org and via well-established RCSB PDB Data, Search, and 1D-Coordinates application programming interfaces (APIs). Simultaneous delivery of PDB data and CSMs provides users with access to complementary structural information across the human proteome and those of model organisms and selected pathogens. API enhancements are backwards-compatible and programmatic users can "opt in" to access CSMs with minimal effort. Herein, we describe modifications to RCSB PDB cyberinfrastructure required to support sixfold scaling of 3D biostructure data delivery and lay the groundwork for scaling to accommodate hundreds of millions of CSMs.

Keywords: FAIR principles; computer architecture; databases; protein structure prediction; structural biology.

Figure 1.

Architectural overview of the RCSB.org web portal. Support for CSMs coming from AlphaFold DB and the ModelArchive was added in September 2022.

Figure 2.

Data API query for CSM metadata on the left, response on the right. (a) Indicates whether this entry is a CSM or a PDB structure. (b) Provides the global pLDDT value. (c) Contains per-residue confidence values.

Figure 3.

Search API query with predicate based on CSM metadata on the left, response on the right. (a) Text query. (b) Filters for very high pLDDT confidence values >90. (c) Requests CSMs.