The scope of the atlas
The published atlas reports 371 catalytic E3 ligases screened and 14 CRL adaptors included, with 243 computationally prioritized ligases and 677 recruiter-anchor hypotheses. These counts describe computational coverage and proposals; experimental binding, productive recruitment and degradation remain separate tests.
Computational screening scope
An additional component class
Computational prioritization
Proposed starting points for testing
- Select for your biology · Focus the map around a target, tissue, compartment and intended functional effect.
- Inspect the anchor hypothesis · Examine why a proposed site and engagement mechanism deserve investigation.
- Choose a discriminating experiment · Find the earliest unresolved step that could change the shortlist.
From ligase information to a recruiter hypothesis
E3 resources already help researchers examine expression, structures, known recruiters and target relationships. BioTwin’s atlas adds its own computational ligase priorities and proposed anchor hypotheses. For a partner, the test is whether those proposals reveal a credible opportunity beyond the recruiter choices already under consideration.
Start with the tissue, compartment and functional effect.
Review proposed engagement, geometry and the reasons to retain each option.
Identify whether binding, productive recruitment or degradation needs evidence first.
- Starting information · Where a ligase is expressed, what its structure suggests and which recruiter systems have been reported.
- A focused evaluation · A target- and tissue-relevant set of hypotheses, the reasons to pursue or reject each, and the evidence that would change the choice.
Binding, recruitment and degradation need different evidence
The E3 research comprises computational opportunities and selected evidence workflows. Candidate anchor sites require experimental engagement evidence. Productive recruitment, ubiquitination, degradation and the intended biological effect are distinct questions.
- Engagement · Can the proposed recruiter bind in the relevant setting?
- Productive complex · Can target and machinery form a useful arrangement?
- Degradation and function · Does the mechanism remove the intended protein and change the biology as required?
Methods for the steps between binding and removal
A recruiter program can call for different scientific operations at different stages.
- E3 recruiter and molecular-glue design · Make the mechanism and its evidence requirements explicit. E3 Recruiter and Molecular-Glue Mechanism Design
- Tether conformer reach · Explore whether an architecture can attain a productive geometry. Tether Conformer Reach and Productive Geometry
- Protein interface analysis · Challenge candidate arrangements against structural and experimental constraints. Constraint-Guided Protein Interface Analysis
Assess the shortlist for your target
Choose a target and tissue, then compare relevant ligase hypotheses with your existing shortlist. A useful evaluation should explain why a proposed recruiter deserves a binding or degradation experiment, and which assumption could remove it from consideration.
