PDBe team Introduces Novel Ligand Pages: A revamped PDBeChem service

New Ligand Pages: Revamped PDBeChem Service (Release)

The Protein Data Bank in Europe team is excited to announce the release of its enhanced PDBe-KB Ligand Pages, an upgraded version of the PDBeChem service featuring new and improved features.

These updated PDBeChem pages provide a comprehensive view of small molecule data, including ligand descriptions, physicochemical properties, ligand-protein complexes, and their functional roles in these complexes. The pages also offer binding interaction statistics, related ligands, and cross-links to other databases. This integrated information is presented to enable researchers to identify patterns in ligand interactions and explore their biological significance.

Explore the new ligand pages for Imatinib (CCD ID: STI) at .

A tutorial for these web pages demonstrates how to use the platform to address various scientific questions and is accessible at .

These ligand-centric pages provide a comprehensive and unified view of small molecule data in the PDB, offering an easy-to-use interface for exploring detailed information for any given ligand in the Protein Data Bank (PDB).

Ligands in the PDB are standardised using a unique identifier and organised into three small-molecule reference dictionaries: 

  1. Chemical Component Dictionary (CCD), maintained by the wwPDB partners, this reference dictionary includes a complete description of the individual chemical components in PDB entries, such as amino acids, nucleotides, and small molecules.
  2. Biologically Interesting Molecule Reference Dictionary (BIRD) includes curated ligands of two or more chemical components (CCDs) that form peptide-like inhibitors, antibiotics, and oligosaccharides. The BIRD descriptions are created during the biocuration of the PDB entries and are maintained by the wwPDB partners.
  3. Covalently Linked Components (CLC), maintained by the PDBe team, provide a complete description of ligands composed of multiple covalently linked chemical components (CCDs). 
Schematic showing the different small molecule reference dictionaries
Schematic showing the generation of the small-molecules reference dictionaries in PDB. CCD and BIRD are generated during the biocuration of the PDB entries at various wwPDB sites while CLC is generated by PDBe CCDUtils.

 

The ligand-centric pages can be queried using CCD, BIRD (PRD), and CLC identifiers, providing a streamlined means to access and explore this data for addressing various biological questions. They present a holistic view of each ligand, covering chemical, structural, interaction, and functional details.

Structure with small molecule bound and mapping to features available on the new PDBe-KB ligand pages
Overview of the key features available on the new PDBe-KB Ligand Pages

 

Key Features:

  1. Detailed Description: The "Description" tab displays essential ligand details, including molecular name, synonyms, formula, and chemical descriptors like IUPAC InChI, InChIKey, and SMILES. It features 2D and 3D structural views, highlighting its overall structure and substructures, including Murcko scaffold and ligand fragments. Additionally, it provides physicochemical properties and highlights cases where a CCD is part of a larger BIRD or CLC entry.
  2. Bound Structures: The "Bound Structures" tab, by default, aggregates data by proteins that are found interacting with the ligand, detailing protein name, UniProt accession, total number of PDB structures, source organism, EC number, and the functional role of the ligand (e.g., drug-like, cofactor-like or reactant-like). Users can select the “Structures� view to explore individual PDB entries. PDB entries where the ligand is part of a polymer are also highlighted.
  3. PDB-wide interaction statistics: The "Interaction Statistics" tab aggregates atom-level interaction data between ligands and proteins in the PDB, showing relative interaction frequency for each ligand atom via a heatmap, with darker green indicating more frequent interactions. The data is also visualised on a 2D ligand image, highlighting interaction hotspots. Both views are interconnected, allowing users to highlight the ligand atom in one view, with the corresponding atom highlighted simultaneously in the other. The heatmap also shows the likelihood of ligand atoms interacting with specific amino acids, with darker purple indicating more frequent interactions. Users can sort the data by amino acid or interaction frequency and filter by interaction type.
  4. Related ligands: The "Related Ligands" tab showcases structurally similar ligands, organised into three categories: same scaffold, �60% similarity, and stereoisomers. Each category includes an image gallery with a link to its 3D view and details such as ligand name, CCD ID, similarity percentage, and the number of PDB structures where these ligands are found. It also includes a link to the PDBe search page, allowing users to filter results by criteria like experimental method, source organism, sequence, and structural classification.
  5. Cross-links to other databases: The "Ligand-specific Databases" tab provides cross-references to other data resources such as ChEMBL, PubChem, KEGG, DrugBank and more, with mapping done through UniChem.

Details about the various PDBe tools used to compute the data shown on these web pages can be found in our recent publication: . These novel Ligand Pages are developed as part of the BioChemGraph project, a collaboration between ChEMBL, , and , to improve the integration between macromolecular and small molecule databases. These pages will also serve as access points for integrated data from the CCDC, ChEMBL, and the PDB. Read more about the BioChemGraph project and its previous release at /about/news/updates-from-data-resources/biochemgraph-data/.