E3 Ligase Atlas / Targeted protein degradation

Could a different E3 ligase open a route to your target?

Most degrader programs begin with a small set of familiar recruiters. BioTwin’s atlas gives teams a broader set of E3 hypotheses to investigate, with proposed engagement sites and explicit questions about whether recruitment could become degradation.

Illustration of two folded proteins meeting at a molecular interface, with a small connecting molecule.

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.

371Catalytic E3 ligases screened

Computational screening scope

14CRL adaptors included

An additional component class

243Ligases prioritized

Computational prioritization

677Recruiter-anchor hypotheses

Proposed starting points for testing

Different measures of the same computational atlas, not a conversion funnel or a count of validated binders.
Previously published atlas scope
  • 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.

Your targetChoose the biological context

Start with the tissue, compartment and functional effect.

A focused shortlistExamine the recruiter hypotheses

Review proposed engagement, geometry and the reasons to retain each option.

The next testResolve the limiting question

Identify whether binding, productive recruitment or degradation needs evidence first.

Illustrative partner-evaluation path through the atlas. It describes how to investigate a shortlist, not a completed target-specific validation campaign.
  • 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.

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.

Discuss a focused scientific evaluation

Tell us the target, the constraint and the decision your team needs to make.