Breakthrough Tracker record
Designed proteins cleaved peptide bonds through two catalytic strategies
Two related Nature studies report wet-lab-validated de novo cysteine proteases and zinc metalloproteases, including sequence-selective cleavage, high rate enhancements and crystal structures close to the intended designs.
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- Stable ID
biology-de-novo-cysteine-metalloproteases-2026- Revision
biology-de-novo-cysteine-metalloproteases-2026.v1- Field
- Biology and chemistry · Protein design, enzymatic catalysis and structural biology
- Evidence
- Tier 1 · Peer reviewed: Yes
- Record state
- Current · Peer-reviewed laboratory result
- Last checked
AI role
RFdiffusion-family generation, sequence design and AlphaFold filtering were central to proposing the proteins; biochemical assays, cellular experiments and structures supplied the decisive evidence.
Record details
- Problem or result
- De novo design of sequence-selective cysteine proteases and zinc metalloproteases
- Authors
- Hojae Choi, Magnus S. Bauer, Samuel J. Pellock, Donald Hilvert, David Baker and collaborators; Anqi Chen, Kejia Wu, Hojae Choi and collaborators
- Institutions
- University of Washington Institute for Protein Design with ETH Zurich, HHMI, LBNL and international collaborators
- Result date
- Both Nature papers published October 14, 2026
Why it matters
Cleaving unactivated peptide bonds has been a difficult de novo enzyme-design target. The paired studies demonstrate two experimentally and structurally tested catalytic routes rather than only binding predictions or activated-substrate chemistry.
Limits
These are laboratory and cultured-cell results, not therapies. The designs remain less efficient than the best natural proteases, and delivery, off-target cleavage, immunogenicity, organism-level efficacy and safety are untested. The two papers substantially share a research ecosystem and are not independent replication.
Sources
- Primary: Nature de novo cysteine-protease study
- Companion primary: Nature computational metalloprotease study
- Data archive: Metalloprotease design and assay archive
Correction and revision history
- 2026-10-19 — Added after primary-source, scope, status, AI-role and limitation review.
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