From sequence difference to reaction hypothesis
A sequence alignment identifies conserved and substituted residues. The BioTwin assessment adds modeled structural and electrostatic context around a proposed handle. A residue can be present in two proteins while its environment differs; absence alone also leaves other off-target routes to consider.
Make the comparison experimental
Current output is a computational selectivity hypothesis. Choose relevant paralogs and variants for a matched counterscreen, separating recognition, reaction rate and exposure when they affect interpretation. Neither a non-conserved handle nor a modeled thiolate change proves selective engagement.
Selectivity has more than one source
Local electrostatic design could change target chemistry, while plasma competition could defeat it before engagement. Combining those questions may reveal why a favorable target/paralog comparison fails in a broader setting. Each component and its inputs need to be checked.
- Local electrostatics · See the scope of ligand-induced pKa design. Local electrostatics
- Competing reactions · Follow the extracellular loss processes that may dominate capture. Competing reactions