University of Washington researchers have introduced RFdiffusion3, a generative model that uses free-atom diffusion to build custom protein and RNA structures around precise geometric constraints. Tested across functional enzyme challenges, the system designed synthetic phosphotriesterases that coordinate two metal ions and zinc-dependent proteases tailored to cut transthyretin, a protein implicated in amyloid diseases. Both enzyme campaigns yielded functional catalysts without iterative rounds of laboratory optimization, producing active hits within 96 tested candidates.
Jasper Butcher, Rohith Krishna, Raktim Mitra, and 30 othersJasper Butcher, Rohith Krishna, Raktim Mitra, Seth M. Woodbury, Donghyo Kim, Rafael I. Brent, Yanjing Li, Nathaniel Corley, Andrew Favor, Anqi Chen, Paul T. Kim, Jonathan Funk, Gabriela Bastidas Reinoso, Kejia Wu, Aiko Muraishi, Helen E. Eisenach, Saman Salike, Simon Mathis, Tuscan Rock Thompson, Antonia Ruder, Enisha Sehgal, Andrew Kubaney, Jie Chen, Yuliya Politanska, Brian Coventry, Odin Zhang, Florence J. Hardy, Bo Qiang, Kieran Didi, Maxwell Kazman, Lars L. Schaaf, Frank DiMaio, David Baker fewer authors
University of Washington; The Novo Nordisk Foundation Center for Biosustainability; Technical University of Denmark; and 5 othersUniversity of Washington; The Novo Nordisk Foundation Center for Biosustainability; Technical University of Denmark; Cambridge; ETH Zurich; Oxford; Howard Hughes Medical Institute; NVIDIA fewer institutions