Nature reports de novo designed cysteine proteases, built on folds unlike any natural enzyme
15 October 2026
A paper in Nature reports the de novo design of cysteine proteases, enzymes that cut other proteins.
The designs were not copied from nature: the reported folds are very different from natural proteases, with a TM score below 0.50.
Of the designs tested, 13 out of 69, or 19 per cent, worked.
Six crystal structures matched the design models closely, with a C-alpha root mean squared deviation of less than 1.2 angstrom.
The work comes from the Institute for Protein Design at the University of Washington, with David Baker, Samuel J. Pellock and Donald Hilvert of ETH Zurich as corresponding authors.
In plain words
De novo design De novo design — Designing a protein from first principles rather than modifying an existing one.
Protease Protease — An enzyme that breaks the bonds between amino acids in a protein.
TM score Template modelling score — A measure of how similar two protein folds are, where a low value means very different shapes.