ActivityFinder: Toward the Fully Automatic Integration of Structural and Binding Affinity Data

The reliable integration of structural and bioactivity
data remains
a significant bottleneck in computational chemistry and cheminformatics.
While curated databases such as PDBbind and ChEMBL provide valuable
resources, integrating structural data in the form of, for example,
PDB files and bioactivity assays in the form of structured data, like
ChEMBL, is inherently complex, and no fully integrated solution has
been published so far. This work introduces ActivityFinder, a fully
automated method for linking protein–ligand crystal structures
to bioactivity assay data without relying on external services or
continuous data connections. The method solely requires structural
information in the form of PDB files and a structured SQL database
such as ChEMBL, making it highly suitable for proprietary or unpublished
data sets typically used within the pharmaceutical industry or early
research in general. ActivityFinder utilizes sequence alignments and
detailed chemical structure matching. Its accuracy is showcased for
the task of associating PDB entries with corresponding data in ChEMBL.
Applying this method, we linked 20197 PDB structures and 13734 ligands
with 17829 unique ChEMBL ligands across 2585 targets, covering over
one million bioactivity data points. Compared to existing approaches
based on identifier mapping, ActivityFinder reproduces reported links
but also broadens the set of linked data by explicitly addressing
ligand heterogeneity, sequence variants, and binding-site mutations
at an atomistic level. ActivityFinder is available via the Rest API
of the ProteinsPlus platform, and the data is published as a PostgreSQL
database dump, enabling scientists to integrate and explore structural
and bioactivity data reliably.