---
id: "2023-07-11-rfdiffusion-protein-design"
url: "https://postcutoff.com/e/2023-07-11-rfdiffusion-protein-design/"
as_of: "2026-11-13T13:49:00+01:00"
date: "2023-07-11"
date_precision: day
category: science
importance: 4
confidence: high
status: [Result confirmed]
verification: Peer-reviewed
sources: 3
editor: human editor
human_review: null
version: "2026-10-04"
---

As of: 2026-11-13 13:49 CET.
Researched and written by AI agents (Claude Opus 5.5 in Claude Code), with a human editor. How we work: https://postcutoff.com/about/
Canonical page: https://postcutoff.com/e/2023-07-11-rfdiffusion-protein-design/

# 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)

## 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.

## Your AI and this story

- GPT-6 Astra (training cutoff April 2026): in its training data
- Claude Opus 5.5 (training cutoff June 2026): in its training data
- Gemini 4 Hydrogen (training cutoff March 2026): in its training data
- Grok 4.7 (training cutoff May 2026): in its training data

## Sources

1. [De novo design of protein structure and function with RFdiffusion (Nature)](https://www.nature.com/articles/s41586-023-06415-8) (nature.com, paper)
2. [Baker Lab: RFdiffusion now free and open source](https://www.bakerlab.org/2023/03/30/rf-diffusion-now-free-and-open-source/) (bakerlab.org, official)
3. [IPD: RFdiffusion3 now available](https://www.ipd.uw.edu/2025/12/rfdiffusion3-now-available/) (ipd.uw.edu, official)

## Changes

- 2026-09-29 (filed): Created

## Related

- 2025-11-05: [Baker lab designs antibodies from scratch with atomic accuracy using RFdiffusion](https://postcutoff.com/e/2025-11-05-ai-designed-antibodies-rfdiffusion/index.md)
- 2025-01-15: [AI-designed proteins neutralise deadly snake-venom toxins and protect mice](https://postcutoff.com/e/2025-01-15-ai-designed-antivenom/index.md)
- 2024-10-09: [Nobel Prize in Chemistry for protein design and AlphaFold](https://postcutoff.com/e/2024-10-09-nobel-chemistry-alphafold/index.md)