Drug discovery
Accelerated Drug ScreeningMaturity: concept
Virtual screening has to be cheap enough to run across a whole library and accurate enough not to throw away good molecules. Docking scores track binding affinity loosely, so shortlists carry false positives you can measure and false negatives nobody ever finds out about. We are working on scoring for the middle of the funnel, tested by whether it ranks known binders highly without being told.
concept — An idea we find credible. Nothing has been built or measured.
What this is
The problem
Virtual screening filters enormous compound libraries down to a shortlist worth synthesising. The filter's job is to be cheap and to avoid discarding good candidates.
Where the current approach strains
Docking scores correlate with binding affinity loosely enough that shortlists carry many false positives, and — more expensively — unknown false negatives. Nobody finds out about a good molecule that was screened out.
What we are exploring
Better scoring for the middle of the funnel, where cheap methods lose reliability and accurate methods are unaffordable at scale.
What would have to be true
Retrospective screening against libraries with known actives: does the method rank the known binders highly without having been told? Enrichment on held-out actives is the standard test and the right one.
Where it applies
Related
Molecular Optimization
Conformation, energy, binding and molecular-property optimisation.
Targeted Drug Design
Binding affinity, selectivity and off-target risk concepts for targeted compounds.
Targeting and Prediction
Protein/biological target identification and interaction prediction.