Choose the uncertain step
Engagement, complex formation, ubiquitination, proteasome engagement, degradation and functional effect require different evidence. Keeping those steps distinct helps a team interpret a promising result without skipping the mechanism.
E3Atlas already provides substantial target-specific ligase information. BioTwin’s question is how a particular recruiter proposal would progress through the mechanism.
| Question | Familiar approach | BioTwin focus | Practical consequence |
|---|---|---|---|
| Starting point | E3Atlas offers target-specific search, localization, expression, structure, interactions and ligandability context. | Computational ligase opportunities and proposed anchor sites are considered for a defined program. | Use the strongest available ligase context when deciding which proposal deserves an assay. |
| What to test | A ligase profile supports selection and interpretation. | The proposal is separated into engagement, productive complex, ubiquitination, degradation and functional effect. | A failed step changes the next experiment and the interpretation of downstream results. |
| Proof required | Resource coverage does not establish a new recruiter’s activity. | Candidate anchors and selected evidence workflows exist; biological mechanism still needs testing. | Evaluate whether the candidate dossier identifies a better-defined experiment. |
The relevant evaluation is whether the candidate-specific mechanism analysis changes the experimental plan.
From atlas hypotheses to mechanism evidence
BioTwin has a computational E3 opportunity atlas and selected operations that connect observations to mechanism requirements. Anchor sites remain hypotheses. Binding or a plausible complex does not establish productive degradation, selectivity or phenotype.
Geometry has a job to do
Linker reach and interface constraints can refine a recruitment hypothesis. Their outputs must refer to compatible target and recruiter structures; a list of methods alone does not establish a working composition.
- Tether geometry · Check the arrangements a linker can attain. Tether geometry
- Protein interfaces · Challenge candidate arrangements with structural and experimental constraints. Protein interfaces
- E3 atlas · Review the published computational scope. E3 atlas