RFdiffusion: diffusion models design new proteins that work in the lab
David Baker's lab (Nature, July 2023) fine-tuned RoseTTAFold as a diffusion model to generate new protein backbones for binders, symmetric assemblies and metal-binding sites. Hundreds of designs were experimentally characterised. A cryo-EM structure of a designed binder bound to influenza haemagglutinin was nearly identical to the design model.
Key facts
- Nature, 11 Jul 2023; code released free and open-source in 2023
- Designs: protein binders, symmetric oligomers, enzyme active-site scaffolds, metal-binding proteins
- Successors: RFdiffusion2 (Nature Methods, Jan 2026: scaffolds for all 41 benchmark active sites vs 16 before) and RFdiffusion3 (open-sourced Dec 2025)
- Part of the work recognised by the 2024 Nobel Prize in Chemistry (Baker)
Science result
- Field
- biology / de novo protein design
- Problem
- Designing proteins with specified shapes and functions from scratch
- Result
- A general generative model whose protein designs fold and bind as intended at high experimental success rates.
- AI system
- RFdiffusion
- Human role
- Human-designed system; humans select and test designs
- Verification
- Peer-reviewed in Nature; lab-validated incl. cryo-EM
- Status
- confirmed
What happened
By adapting image-generation-style diffusion to protein structures, the Baker lab made protein design largely a matter of generating and filtering candidates on computers.
Why it matters
It became the workhorse of AI protein design, underlying AI antivenoms, antibodies and enzymes.
Changelog
- 2026-09-29: created
Related events
- Nobel Prize in Chemistry for protein design and AlphaFold ★★★★★
- AI-designed proteins neutralise deadly snake-venom toxins and protect mice ★★★
- Baker lab designs antibodies from scratch with atomic accuracy using RFdiffusion ★★★
- ESM3 generates esmGFP, a new fluorescent protein estimated at '500 million years of evolution' from nature ★★★
- AlphaProteo designs high-affinity protein binders, including the first AI-designed VEGF-A binder ★★★
Sources (3)
- paperDe novo design of protein structure and function with RFdiffusion (Nature)
- officialBaker Lab: RFdiffusion now free and open source
- officialIPD: RFdiffusion3 now available
id: 2023-07-11-rfdiffusion-protein-design · updated 2026-09-29 · open in the interactive timeline