# RFdiffusion / RFdiffusion2 and ProteinMPNN (Baker Lab)

Source: https://onco.cc/technologies/rfdiffusion/  
OnCo record `rfdiffusion` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The tools that design entirely new proteins to bind a chosen target, now used for cancer binders and antibodies.

## Summary

RFdiffusion and ProteinMPNN from the Baker Lab are the core tools of de novo protein design. RFdiffusion (Nature 2023) uses denoising diffusion to generate protein backbones conditioned on a target, ProteinMPNN then designs an amino acid sequence to fold into that backbone, RFdiffusion2 (2025) extends the approach to enzyme design, and RFantibody extends it to antibodies. Together they are the basis of Xaira Therapeutics and many binder programmes, including designed binders against cancer targets. The strength is validated de novo binders that have been made and shown to bind in the lab. Developability and immunogenicity of designed proteins remain empirical questions answered only by experiment, so each design still has to be made and tested. For a newcomer: these tools invent new proteins shaped to grab a chosen target, and several have already worked in the lab.

## Fields

- Kind: Technology
- Status: emerging
- Last checked: 2026-09-08
- Tags: foundation-model; protein-design
- Principle: Denoising diffusion over protein backbones conditioned on a target.
- Since: 2023
- Strengths: Validated de novo binders
- Limitations: Developability and immunogenicity still empirical

## Sources

- Nature 2023: https://doi.org/10.1038/s41586-023-06415-8

## Connected records

- fronts: [AI & Computation](https://onco.cc/fronts/ai-computation/), [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/)
- technologies: [AI-driven drug & target discovery](https://onco.cc/technologies/ai-drug-design/)
- companies: [Xaira Therapeutics](https://onco.cc/companies/xaira-therapeutics/)
- institutions: [Institute for Protein Design (University of Washington)](https://onco.cc/institutions/institute-for-protein-design/)
- key papers: [De novo design of protein structure and function with RFdiffusion](https://onco.cc/key-papers/paper-watson-nature/)
- roadmaps: [AI in oncology roadmap: pattern readers → foundation models → agents in the workflow](https://onco.cc/roadmaps/ai-oncology-roadmap/), [Drug discovery roadmap: screening in mice → maps of dependency → designing in silico](https://onco.cc/roadmaps/drug-discovery-roadmap/)

---
JSON: https://onco.cc/api/v1/entities/rfdiffusion.json