PXDesign
Binder design with JAX AF2 Initial Guess validation. Real ipTM, pLDDT, and pAE from the AF2 monomer model run in initial-guess mode against the target. Pilot runs in roughly 30 to 60 min.
What it is for
Pick PXDesign when AF2 confidence against a defined target matters and you want real ipTM, pLDDT, and 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.
PXDesign is a Ranomics in-house binder-design pipeline. An RFdiffusion-style backbone generator paired with JAX AF2 in Initial Guess mode for fast, accurate scoring (Bennett et al., Nature Communications 2023). Every candidate carries real ipTM, pLDDT, and pAE from the AF2-IG stage.
When it fits:
- AF2 confidence against a defined target matters and you want real ipTM, pLDDT, and pAE on every candidate.
- You want faster scoring than full AF2 multimer (Initial Guess shortcut).
- You want the same scoring pipeline that drives Ranomics' 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 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.
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.