De novo cysteine proteases published in Nature with 19% design success rate
JosephJacks_ · x · 2026-10-20
- Researchers report de novo design of cysteine proteases — enzymes that cut other proteins — published in Nature, with code released.
- Starting from a Cys-His-Asp catalytic motif, they used RFdiffusion-based generation (RFD2-MI) to create entirely new folds across parallel, anti-parallel, and sandwich strand-pair topologies.
- Activity was validated in mammalian cells via an enzyme-substrate-mScarlet reporter; 13 of 69 designs succeeded (19% success rate), with designs named Gawi, Kal, and Dokki.
- The reposter frames it as evidence that biotech is smoothly becoming nanotech: programmable matter and living things interoperable with the machine world.
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