BindCraft
Upload your target structure, mark the residues you want gripped, and get back new mini-proteins of 50 to 150 residues built to grip them, already refolded and filtered. Results are emailed when they finish.
What it is for
You have a target structure and know roughly which patch of its surface you want gripped, and you want brand-new mini-proteins of 50 to 150 residues built to grip it. Every candidate is refolded and filtered before you see it, so what comes back is already a shortlist.
Designs brand-new mini-proteins that grip a patch of your target. It runs AlphaFold2 multimer backwards — pushing a random starting sequence toward one the model believes will bind the residues you named — then assigns a real sequence with ProteinMPNN and refolds every candidate to check the answer survives. What reaches you has already been filtered on interface confidence and fold quality. BindCraft, Pacesa et al., Nature 2025.
When it fits:
- You have a target structure and at least one residue on its surface you want the binder to touch.
- You want a small de novo protein of 50 to 150 residues, not an antibody.
- You would rather see a filtered shortlist than every candidate the run generated.
Inputs
You will need:
- Target structure as
.pdb,.cif, or.mmcif. - Chain ID of the target within that structure.
- At least one hotspot residue index on the target chain.
Each run uses a preset that sets the scale and scope:
- Your target, a small batch on a small target
- BindCraft against your uploaded PDB on A100-80GB. Pick 1 to 500 trajectories. Start with a small batch (4 trajectories) to confirm your target and hotspots, then scale up. A batch too long for the limit one run is stopped at is refused when you submit it, and the refusal names a count that fits — about 5 trajectories on a 320-residue target, 2 on a 500-residue one. A small target is not refused at any count: batches run in groups of 6, and 6 trajectories fit the limit up to about 300 residues. Results emailed on completion.
Parameters you set on the form:
- Hotspot residues
- Comma-separated target-chain residue indices the binder should contact (e.g.
54,56,115). These bias AF2 backpropagation toward the intended epitope. Click residues in the 3D viewer to toggle them. - Binder length (min/max)
- Residue-count window for the generated binder chain (50 to 150). Shorter binders are easier to validate in yeast display; longer ones can target larger interfaces.
- Number of designs
- How many final filtered designs to return (1 to 500). Each passes AF2 re-prediction with ipTM and pLDDT above the BindCraft default thresholds. Runtime scales with the count: start with a 4-trajectory batch to confirm your target and hotspots, then scale up.
How to read the results
Filtered candidate binders with ipTM, pLDDT, shape complementarity, and PDBs downloadable from a run of your own. An ipTM of 0.75 or more is a credible binder and 0.85 or more is a strong candidate. Hand off promising designs to the Ranomics yeast display CRO for in vitro validation.
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 — this guide's own results summary above states this tool's. 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
Pacesa et al., Nature 2025