AI designs proteases that cut up specific proteins

Researchers in David Baker's lab at the University of Washington used AI protein-design tools RFdiffusion2 and ProteinMPNN to build proteases that cleave chosen proteins. They tested 135 designs for a zinc protease and 12 backbones for a cysteine protease, and demonstrated cuts on proteins linked to neurological diseases.

• AI design replaced everything around the catalytic core of two natural proteases
• 135 designs tested for the zinc protease; 12 backbones and 69 amino-acid sets for the cysteine one
• AlphaFold3 confirmed the structures don't match known proteins in databases
• The enzymes target proteins associated with neurological diseases