PXDesign
Upload your target structure, mark the residues you want gripped, and get back binders that each carry a real AlphaFold2 confidence score against that target. A pilot run takes roughly 30 to 60 min.
What it is for
You have a target and you want every single candidate to arrive with a real AlphaFold2 confidence score against that target, not a cheaper stand-in. This is the pipeline Ranomics runs for its own wet-lab campaigns. For design without that filtering step use BindCraft; for antibody formats use RFantibody or IgGM.
Designs binders against your target and then scores every one of them with AlphaFold2 run against that same target, so nothing reaches you on a cheaper stand-in number. The scoring uses AlphaFold2's initial-guess mode, which is far quicker than a full multimer prediction and is what makes per-candidate scoring affordable at all. This is the pipeline Ranomics runs for its own wet-lab campaigns. PXDesign is in-house; the initial-guess method is Bennett et al., Nature Communications 2023.
When it fits:
- You want an AlphaFold2 confidence number against your actual target on every candidate, not on a filtered subset.
- You want that scoring faster than a full AlphaFold2 multimer run on each design.
- You want the same pipeline Ranomics runs for its own wet-lab campaigns.
Inputs
You will need:
- Target structure (
.pdb/.cif). - Chain ID of the target.
- At least one hotspot residue.
Each run uses a preset that sets the scale and scope:
- Pilot run on your target, ~45 min
- Real PXDesign run against your uploaded target with AF2-IG validation. Up to 24 candidates with real ipTM, pLDDT, and pAE scores; results emailed when complete (~30 to 60 min on A100-80GB).
Parameters you set on the form:
- Hotspot residues
- Comma-separated target-chain residues defining the epitope. Click in the 3D viewer to toggle.
- Binder length
- Residue count for the generated binder. ~40 residues is the validated default; PD-L1 published binders are in this range.
- Number of designs
- How many candidates to score. Higher counts increase cost and runtime linearly.
Typical runtime:
- pilot
- 30 to 60 min
How to read the results
Ranked candidates with ipTM, pLDDT, pAE, and downloadable PDBs. Target ipTM ≥ 0.70 on 1 to 2 of 5 designs for a tractable epitope.
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: > 0.75 strong; > 0.65 acceptable. 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
Bennett, N. R., Coventry, B., Goreshnik, I., et al. "Improving de novo protein binder design with deep learning." Nature Communications 14, 2625 (2023). Ranomics in-house pipeline; scoring stage uses AF2 Initial Guess.