Recognition still comes first
The research toolkit considers serine, threonine, tyrosine, lysine and histidine-directed hypotheses alongside geometry, hydrolysis and competing thiol reactivity. The aim is a residue-and-warhead pairing that earns a chemistry experiment. Simply replacing one electrophile with another is insufficient.
A demonstrated planning step
An executed BioTwin planning example surfaced non-cysteine chemistry when accessible cysteine was excluded, together with interface, allosteric and recruitment alternatives. That demonstrates candidate guidance with requirements to review. It does not establish a successful non-cysteine compound or complete automatic filtering of unsuitable routes.
Compare more than target reactivity
A matched series should test recognition, target reaction, hydrolysis and competing reactions. Paralog analysis and plasma-competition models could help choose the counterscreens; the joined calculation needs target-specific inputs.
- Covalent selectivity · Identify related proteins that challenge the hypothesis. Covalent selectivity
- Plasma competition · Assess a proposed extracellular reaction against competing losses. Plasma competition