Nature, Published online: 14 October 2026; doi:10.1038/s41586-026-11167-2

RFdiffusion methods are used to de novo design proteins with water-activating zinc-based active sites adjacent to a peptide substrate binding pocket, yielding highly active, programmable proteases with potential applications in therapeutics, biotechnology and bioremediation.

Nature, Published online: 14 October 2026; doi:10.1038/s41586-026-11167-2

RFdiffusion methods are used to de novo design proteins with water-activating zinc-based active sites adjacent to a peptide substrate binding pocket, yielding highly active, programmable proteases with potential applications in therapeutics, biotechnology and bioremediation.