protein design — papers · Status Papers

BiologyNature · Jul 2023 Open access

De novo design of protein structure and function with RFdiffusion

Joseph L. Watson, David Juergens and David Baker

This paper introduced RFdiffusion, a generative diffusion model built on the RoseTTAFold network for de novo protein design. It enables a range of design tasks, including unconditional generation, symmetric oligomer design, functional motif scaffolding, and binder design. Many designs were experimentally validated, with solved structures closely matching the intended models.

protein design de novo design diffusion model rfdiffusion

BiologyScience · Oct 2020 Open access

De novo design of picomolar SARS-CoV-2 miniprotein inhibitors

Longxing Cao, Inna Goreshnik, Brian Coventry and David Baker

The authors used computational de novo protein design to create small, stable miniproteins that bind the SARS-CoV-2 spike receptor-binding domain and block its interaction with ACE2. Two design strategies were used: incorporating the ACE2 helix into a designed scaffold, and building entirely new binders against the RBD. The best designs bound with picomolar affinity and neutralized the virus, with cryo-EM confirming the binding modes matched the computational models.

protein design sars-cov-2 miniprotein inhibitors ace2