Drug discovery
Targeted Drug DesignMaturity: concept
Binding affinity, selectivity and off-target risk concepts for targeted compounds.
concept — An idea we find credible. Nothing has been built or measured.
What this is
The problem
Structure-based design starts from a target's three-dimensional structure and designs a molecule to fit. It works when the structure is known, well-resolved, and does not move much.
Where the current approach strains
Many interesting targets are flexible, disordered, or membrane-bound and hard to resolve. Binding-site prediction on those is unreliable, and the errors compound through everything downstream.
What we are exploring
Interaction modelling for targets where structural data is partial — the cases where current methods are weakest and the potential value is highest.
What would have to be true
Validation on targets whose structures were solved after the prediction was made. Anything retrospective risks having seen the answer.
Where it applies
Related
Accelerated Drug Screening
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.
Molecular Optimization
Conformation, energy, binding and molecular-property optimisation.
Targeting and Prediction
Protein/biological target identification and interaction prediction.