RFD4-Proteina
Upload your target structure, mark the residues you want gripped, and get back binders whose sequence and all-atom structure come out of one model, with no separate sequence-design step.
What it is for
You have a target structure and want a binder that arrives whole. RFD4-Proteina writes the sequence and the all-atom structure in a single model, so there is no separate sequence-design step to run afterwards. It returns no confidence number: judging the complex is a fold run of its own. For a route that sequences and refolds the backbone for you, so each candidate arrives with an AlphaFold2 confidence score, use RFdiffusion; for a backbone with its own designability screen use Proteina; for an antibody or nanobody format use RFantibody or IgGM.
Designs de-novo protein binders against a patch of your target structure, and writes each binder's sequence and its full atomic structure in one model, so a design comes back complete rather than as a backbone waiting for a sequence step. RFD4-Proteina, Corley et al., preprint 2026.
When it fits:
- You want a small de-novo binder against a protein target, not an antibody format.
- You would rather have sequence and structure out of one model than run a separate sequence-design step.
- You have your own way of judging a complex. This tool hands back structures and no score.
Inputs
You will need:
- Target structure (
.pdb/.cif). - Chain ID of the target. One chain only.
- At least one hotspot residue on that chain.
Each run uses a preset that sets the scale and scope:
- Protein binder (de novo, vs your target chain)
- Hotspot-conditioned binder design against one chain of your uploaded structure. Sequence and all-atom structure are generated together, so a design arrives complete rather than as a backbone still needing a sequence step. Runs on our GPUs.
Parameters you set on the form:
- Hotspot residues
- Residues on the target chain the binder should grip, in the uploaded file's own numbering. At least one is required.
- Binder length (residues)
- The binder length range you give. Anywhere between 20 and 300 residues; the default range is 60 to 120.
- Number of designs
- How many binders to generate. Each one is an independent sample, and each is delivered as a structure file holding your target chain plus the binder.
How to read the results
One structure per design, each holding your target chain and the de-novo binder beside it, downloadable from a run of your own. There are no score columns: nothing in this run measures how well a binder holds, so take the structures into a predictor before choosing between them.
Where a tool reports them, the scores mean:
- ipTM
- Predicted confidence in the contact between two chains, on a 0 to 1 scale. Higher is better: 0.65 to 0.75 depending on the tool. Individual tools set their own pass bar a little either side of that. On a multi-chain target the number may cover the target's own chain–chain interface as well as the binder's, so read the per-tool note on the results table before comparing designs on it.
- 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.
References
Corley et al., preprint 2026