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ChEMBL brings drug bioactivity data to the Protein Data Bank in Europe

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In the quest to develop new drugs, understanding the 3D structure of molecules is crucial. Resources like the Protein Data Bank in Europe (PDBe) and the Cambridge Structural Database (CSD) provide these 3D blueprints for many biological molecules. However, researchers also need to know how these molecules interact with their biological target – their bioactivity.

ChEMBL is a treasure trove of bioactivity data for countless drug-like molecules. It tells us how strongly a molecule binds to a target, how it affects a biological process, and even how it might be metabolized. But here's the catch: while ChEMBL provides extensive information on a molecule's activity and cross references to other data sources, it doesn't always tell us if a 3D structure is available for a specific drug-target complex. This can be a roadblock for researchers who need that structural information to design effective drugs. Therefore, connecting ChEMBL data with resources like PDBe and CSD is essential to accelerate drug discovery.

The BioChemGraph (BCG) project tackles the challenge of linking diverse data in biology by creating a resource that integrates data from the PDBe, ChEMBL, and the CSD. This project builds upon the PDBeKnowledge Base (PDBe-KB) resource and combines structural, functional, and biochemical information for small molecules and their targets. By using common data standards and providing easy access through APIs and files, BioChemGraph promotes interoperability and opens up new research opportunities by improving the findability and accessibility of small molecule data.

Unifying bioactivity and structural data to accelerate drug discovery

Using unique identifiers like UniProt Accession numbers for proteins and InChIKeys for compounds, we've successfully connected over 17,000 experimentally determined protein-ligand complexes from the PDB to approximately 39,000 ChEMBL bioactivity records. These ChEMBL records provide a diverse range of experimental measurements, encompassing binding affinities, functional assays, and various inhibition and antagonism studies.

Crystal structure of ABL kinase (PDB: 2HYY) in complex with imatinib. The BCG simple report shows the mean pChEMBL value of 6.998 for this complex, wich is calculated from all available bioactivity data for the complex in ChEMBL


The integrated data is presented in two formats: a full report with all data in ChEMBL available for a given complex and a simple report with a mean pChEMBL value providing a standardised measure of compound potency derived from the relevant activity data in ChEMBL. The pChEMBL value helps put the compound activities on a consistent scale, making it easier to compare, assess and rank the potency of different compounds across various bioassays.
This powerful synergy enables researchers to delve deeper into drug mechanisms, identify promising drug candidates, and explore potential drug repurposing opportunities.
The dataset is now available on the FTP server,  with all bioactivities reported in a full report and a simplified version with aggregated values for each target-ligand complex. Besides, direct links to individual data items in the ChEMBL data resource are available to facilitate further exploration. Data will be updated weekly, in sync with the PDBe release every Wednesday at 00.00 UTC.

CSD data is now linked to ChEMBL via UniChem

To further enhance the applicability of CSD data, the BioChemGraph initiative has now linked over 235,000 CSD identifiers to their corresponding entries in UniChem.
To enable this integration, the Cambridge Crystallographic Data Centre (CCDC) team developed a protocol that generates reliable InChIs for CSD entries via the CSD Python API, utilising 2D diagrams for connectivity and 3D models for stereochemistry. An automated pipeline ensures that CSD InChIs are shared with the ChEMBL team to support regular updates of the UniChem service.
By integrating CSD identifiers in UniChem, it is now easier to identify the availability of crystal structures that contain a specific molecule of interest. As a result, links to crystal structures in the CSD will be integrated into the PDBe-KB for around 32,000 small molecules present in either ChEMBL or PDBe.

Towards a unified vision of molecular data

By bridging the gap between small molecule data resources and macromolecular information (PDB), BioChemGraph empowers researchers to explore the intricate relationships between these structural domains. This will ultimately accelerate research in diverse fields, including drug discovery materials science, and advance our understanding of fundamental biological processes.


BioChemGraph’s training material is now available! -> BCG Training
More information can be found in the official EBI communications article. -> Read article




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