What it is for

You have a hard target — a recessed pocket, a site spanning two chains, or a small molecule rather than a protein — and you want to throw as much search at it as your balance allows. Every candidate is re-folded and scored against your target as it is generated, and the run fans out across as many GPUs as you fund.

Designs binders for the targets the standard tools find hard: a recessed pocket, a site spanning two chains, a small molecule instead of a protein, an enzyme active site. Rather than generating candidates and hoping, it searches — it generates, re-folds every candidate and scores how well it grips your target, keeps what scores well and generates again from there. Which model does that scoring follows the target: a protein target is scored by an AlphaFold2 refold, a small-molecule or motif target by RoseTTAFold3, with a physics force field added where it applies. The run splits into independent shards across as many GPUs as your balance funds, then ranks globally across all of them and clusters the winners, so you get a spread of different designs rather than many copies of one. Proteina-Complexa, Geffner et al., NVIDIA 2025.

When it fits:

You want to aim a binder at one specific patch, including a recessed or partly shielded one, by naming residues on it.
The site you care about spans more than one chain of your target.
Your target is a small molecule rather than a protein.
You would rather pay for a search that filters as it goes than for raw generation you have to filter afterwards.
You want to scale the search across many GPUs, with your prepaid balance as the only ceiling.
You want a spread of different good designs rather than many variations on one.

Inputs

You will need:

A target: your own structure (.pdb/.cif) for the protein-binder variant, or a curated benchmark task for any variant.
For your own target, the chain ID — or a chain/residue range such as A1-150, or A12-157,B12-157,C12-157 for a multi-chain target.
Optionally, hotspot residues to aim the binder at a specific epitope.
A funded wallet that covers at least the first wave of shards.

Each run uses a preset that sets the scale and scope:

Protein binder (de novo, vs a protein target): Design de novo binders against a protein target. Search is scored by AlphaFold2 confidence plus a force-field reward. Pick a curated target task or upload your own target PDB.
Ligand binder (de novo, vs a small molecule): Design de novo binders against a small-molecule target supplied as an SDF. Scored by the RoseTTAFold3 reward (the force field does not support protein-ligand complexes). Pick a curated ligand task or upload your own SDF.
Motif scaffolding / enzyme (AME): Scaffold a functional motif or enzyme active site. Scored by the RoseTTAFold3 reward. Pick a curated AME task or upload your own motif.
Validate (free dry-run): Free CPU-only pre-flight that checks your target + config load before you commit GPU to a paid search. No wallet charge.

Parameters you set on the form:

Design variant: protein_binder for a protein target (AF2 reward), ligand_binder for a small-molecule SDF target (RF3 reward), motif_ame for motif scaffolding / enzyme active sites, or validate for a free config check before spending GPU.
Target: Your own structure, or a curated benchmark task whose target is baked in — the two are mutually exclusive. Uploading your own is available on the protein-binder variant; the ligand and motif variants run curated tasks (their tasks resolve from separate upstream registries).
Target region: Which chains and residues to design against, e.g. A1-150, or A12-157,B12-157,C12-157 for a multi-chain target. Blank uses the whole target chain.
Hotspot residues: Optional. Residues the binder should contact, in original PDB numbering — plain numbers use the target chain, or prefix the chain (A113 C73) for a multi-chain region. Every hotspot is checked against your structure before any GPU runs, so a residue that is not there is refused rather than quietly ignored.
Binder length: The range each design's length is drawn from. Defaults to 60-120 residues.
Number of designs: How many designs to search for. This scales the number of independent search shards; each shard runs on its own GPU and returns its survivors, and the hub picks the global top set.

Typical runtime:

protein_binder: ~9 to 15 min / shard (measured at 130-415 residues)
ligand_binder: not yet measured (under 120 min / shard)
motif_ame: not yet measured (under 120 min / shard)
validate: 1 to 3 min (free)

How to read the results

Ranked designs with reward scores (AF2 pLDDT / ipTM for protein, RF3 score for ligand / motif, force-field energy where applicable), a structural diversity cluster id, and downloadable structures. The ligand and motif variants score on RF3 only.

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

Geffner et al., NVIDIA (2025)

Read the paper Source code on GitHub

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