Scientists just used AI to invent molecular scissors from scratch — enzymes that find a protein sequence you choose and cut it.
David Baker of the University of Washington and colleagues designed cysteine and zinc proteases de novo, Phys.org reported Oct. 16, citing two papers in Nature. The pipeline stacked an RFdiffusion2 variant called RFD2-MI for 3D shapes and backbones, ProteinMPNN / EnhancedMPNN for sequences, and AlphaFold 3 to check the folds.
They tested the designs in bacteria: each enzyme linked to a target sequence plus a glowing marker. Success meant the enzyme cut the target and freed the marker. For cysteine proteases, 13 of 69 candidates worked. For zinc proteases, 36% of 135 candidates cut matching peptide targets. AI refinement then boosted the top zinc protease’s cutting speed 30×, and a cysteine design cut at precisely the intended site.
Therapeutic promise — not clinical trials yet — showed up in the lab: one design cut full-length TDP-43 (the protein that builds up in ALS and some dementias); others cut amyloid-beta fragments linked to Alzheimer’s and serum amyloid A tied to systemic amyloidosis.
The team’s verdict, as reported: “Our results show that de novo enzyme design has advanced well beyond model reactions on activated substrates.” And: “The ability to design selective proteases for prescribed epitopes on proteins could be transformative for many potential applications.”
The papers: Anqi Chen et al., Computational design of metalloproteases (DOI 10.1038/s41586-026-11167-2); Hojae Choi et al., De novo design of cysteine proteases (DOI 10.1038/s41586-026-11143-w).
Custom scissors for the proteins that make people sick. It’s early, but Nature just put two stamps on it.
Sources: Phys.org — AI molecular scissors that cut proteins · Nature — Chen et al., Computational design of metalloproteases · Nature — Choi et al., De novo design of cysteine proteases
Featured image: AI-generated editorial illustration by Bugle Blast.
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