Run RFdiffusion online

RFdiffusion — de novo binder design — Composite binder design: RFdiffusion backbones + ProteinMPNN sequences + AF2 multimer validation. Candidates carry real ipTM / pLDDT / i_pAE scores. Pilot ~15-30 min on caller targets.

RFdiffusion is a RFdiffusion de novo binder design online you can run through tools.ranomics.com on a dedicated GPU. Run RFdiffusion plus AF2 multimer scoring through your browser without an A100.

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New accounts start with a $5 wallet balance. Pay by the second of compute. No subscriptions.

When to pick this tool

Pick RFdiffusion when you want general de novo binder design scored by AF2 multimer (ipTM / pLDDT / i_pAE). For antibody and nanobody scaffolds use RFantibody, for AF2-IG initial-guess scoring use PXDesign, and for hallucination-driven binders without AF2 filtering use BindCraft.

What it is

RFdiffusion (Watson et al., Nature 2023). Diffusion-based backbone generator. The Ranomics composite pipeline pairs it with ProteinMPNN sequence design and AF2 multimer scoring, so every candidate carries real ipTM / pLDDT / i_pAE statistics from the AF2 re-prediction stage.

When it fits:

  • You want general de novo binder design with AF2-grounded scoring.
  • Your target is a standard protein epitope (no glycans, no PTMs).
  • You want flexible binder length and topology rather than an antibody scaffold.

A typical result

Screenshot placeholder. After sign-in, jobs land at /jobs/<id> with ranked scores, downloadable PDB / FASTA artifacts, and a one-click handoff into the next tool in the pipeline.

What good looks like

Use the score legend below to read results. Each tool reports a subset of these depending on whether it does design, sequence recovery, or structure prediction.

ipTM
Predicted confidence in the binder to target interface. Higher is better. Aim above roughly 0.7 on a tractable target.
pLDDT
Per-residue confidence in the predicted fold. Higher means the model is more sure of that part of the structure.
i_pAE and pAE
Predicted alignment error, at the interface (i_pAE) or across the whole structure (pAE). Lower is better.
ProteinMPNN recovery
Fraction of native residues recovered when ProteinMPNN redesigns a known sequence on its native backbone. Higher is better; well calibrated above roughly 0.4 on diverse folds.

Typical runtime

15-30 min per run on a dedicated GPU. Billing is by the second of compute, so a faster preset costs less.

Learn how RFdiffusion works

We keep a plain-English overview of RFdiffusion on the main Ranomics site — what the model does under the hood, the kinds of targets it works on, and where it fits inside a full design-to-wet-lab campaign.

How RFdiffusion works at Ranomics

Related tools on Ranomics

If you are picking between RFdiffusion and a sibling algorithm, these run on the same hub against the same target.

Run BindCraft online
Pick BindCraft when you have a target PDB plus known hotspot residues and want de novo 60-150 aa protein binders.
Run PXDesign online
Pick PXDesign when AF2 confidence against a defined target matters and you want real ipTM / pLDDT / pAE on every candidate. For hallucination-driven binder design without AF2 filtering use BindCraft, for antibody and nanobody CDRs use RFantibody, and for target structure generation without binder design use BoltzGen.
Run BoltzGen online
Pick BoltzGen when you want one model that can design mini-proteins, nanobodies, antibodies, or peptides against the same target, or when your target involves glycans, post-translational modifications, or non-canonical residues.

Questions people ask about RFdiffusion

Can I run RFdiffusion online without installing it locally?
Yes. Ranomics Tools runs the full RFdiffusion + ProteinMPNN + AF2 multimer pipeline on a dedicated GPU through your browser. You upload a target PDB, set hotspots and binder length, and candidates come back with real ipTM, pLDDT, and i_pAE scores.
How much does one RFdiffusion run cost?
Billing is by the second of dedicated GPU time. A pilot run (~15 to 30 minutes on an A100) typically clears for under a few dollars from your wallet. New accounts start with a $5 balance, which covers a first small-target run.
Do I need to choose hotspots before running RFdiffusion?
Hotspots are strongly recommended — they tell RFdiffusion which residues on the target the binder should contact. If you do not have a hotspot guess, run Epitope Scout first to score the target surface, then hand off the picked residues into the RFdiffusion form.

References

Watson, J. L., Juergens, D., Bennett, N. R., et al. "De novo design of protein structure and function with RFdiffusion." Nature 620, 1089-1100 (2023). Composite pipeline: RFdiffusion backbones + ProteinMPNN sequences + AF2 multimer validation.

Ready to run it?

Sign in to open the RFdiffusion run form. Your $5 starting balance is enough for a first job on a small target.