Understanding compound selectivity with data-driven drug design

Selectivity is a crucial property in the development of new active pharmaceutical ingredients (APIs). Binding site comparisons within a protein family are key to modulating the selectivity profile of a potential new API, which includes understanding both on- and off-target effects. This white paper outlines the importance of data-driven-drug design to maximise compound selectivity.

Researchers at Oxford, Exscientia, and CCDC recently leveraged the hand-curated, experimentally derived data in the Cambridge Structural Database (CSD), the CCDC software suites CSD-Core and CSD-Discovery, and the CSD Python API to automate “ensemble hotspot maps,” which highlight conserved interactions and, potentially, selectivity pockets across multiple protein confirmations.

Ensemble hotspot maps summarize important fragment-binding interactions. Such information can guide computational workflows that allow researchers to rapidly explore the chemical space for lead compounds.