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Purna can design a novel protein from scratch for a target small molecule. Give it a SMILES string, and it generates an amino acid sequence together with a co-folded 3D structure, then independently refolds the design as a sanity check. The resulting files remain available in your session. Enzyme design is powered by DISCO (DIffusion for Sequence-structure CO-design), a diffusion model that jointly generates sequence and structure conditioned on a ligand. Designs are refolded with NVIDIA Boltz-2 and rendered with Mol*, the same viewer used by RCSB PDB.

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Starting a design

Ask Purna to design a protein for a substrate or ligand:
  • “Design an enzyme that binds caffeine”
  • “Design a protein that catalyses cyclopropanation of styrene — use ethyl diazoacetate as the carbene source”
  • “Design 3 scaffolds for this SMILES: CN1C=NC2=C1C(=O)N(C)C(=O)N2C”
Purna resolves the SMILES (pulling it from PubChem or ChEMBL if you give a common name), confirms parameters with you, estimates the GPU cost, and submits the job. The chat shows a compact submission entry. Use Compute or Jobs to follow progress, and open completed outputs from Files.

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Input options

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Motif scaffolding

If you already know the catalytic residues you want to preserve, pass them inside proteinSequence. Fixed positions hold their amino acid, - positions are designed by DISCO.
  • "----------S----------H----------D----------" pins a Ser/His/Asp triad and lets DISCO scaffold the rest.
  • "MKGH----------------------------GGHM" fixes terminal residues and designs everything between.

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Review the generated design

When the job completes, Purna adds the generated artifacts to Files. Open a file to inspect it in a notebook tab, or download it for use in another tool. A completed design can include the following outputs and measurements.

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Design target

The ligand’s canonical SMILES and, when available, a rendered 2D structure.

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3D structure

Open a generated CIF or PDB file to inspect the designed protein backbone and co-folded ligand in Mol*. Residues whose Cα lies within 5 Å of the ligand may be identified in the accompanying analysis. Runs with multiple designs create separate outputs for the generated seeds.
DISCO outputs backbone-only structures (N, Cα, C, O) — no sidechains. Highlighted residues are positional candidates near the ligand, not confirmed catalytic residues. Experimental characterisation is always required.

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Structure composition

A compact bar chart of helix, sheet, and coil fractions computed from the backbone with Biotite.

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Physical and chemical properties

Four sequence-derived numbers: molecular weight, isoelectric point, hydropathicity (GRAVY), and Guruprasad instability index. A collapsible Sequence-derived heuristics section underneath shows charge at pH 7, extinction coefficient, aromatic fraction, and rough suggestions for ion-exchange buffer conditions. These are heuristics from the amino acid sequence, not predictions of expression behaviour.

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Model confidence

DISCO’s native confidence scores — ranking score, inter-chain ipTM, and steric-clash flag when present.

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Boltz-2 validation

Every design is automatically refolded with Boltz-2 to independently predict the structure from sequence and ligand. Purna then computes the backbone RMSD between DISCO’s structure and Boltz-2’s prediction. Use the reported RMSD together with the generated DISCO and Boltz-2 structure files when comparing the intended design with its refolded prediction. You can open each structure in Purna or download the files for a dedicated structural-comparison workflow.

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Designed sequence

The amino acid sequence in monospace, color-coded by property group (hydrophobic, positive, negative, polar, Cys, Gly, Tyr). Residues with their Cα within 5 Å of the ligand are highlighted in emerald. Hover any residue to see its position and near-ligand status.

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Downloading results

The generated files can include:
  • FASTA — the designed protein sequence as FASTA, ready for gene synthesis
  • CIF / PDB — the full co-folded structure, openable in Mol*, PyMOL, or ChimeraX
Each design is saved in Files for the current session or project. You can open or download the artifacts from there.

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How it works

  1. Validation — Purna parses your SMILES with openchemlib, rejects invalid input before any GPU spins up, and uses the canonical form so equivalent SMILES hit the dedup cache.
  2. Submission — The DISCO input JSON is sent to a dedicated Cerebrium GPU (NVIDIA L40). Identical jobs submitted within 10 minutes return the existing result.
  3. Design — DISCO runs effort diffusion steps with the configured number of recycles. Typical runtime is 15–60 minutes for effort=max on a 150–250 residue protein, scaling linearly with numDesigns.
  4. Storage — Each design (CIF and FASTA) is uploaded to cloud storage.
  5. Validation — A Boltz-2 refolding job is dispatched automatically. Its results are saved with the other design outputs when available.
  6. Billing — Charged at 10 credits per second of actual GPU time (including cold start), rounded up to the nearest minute.

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Limits and guardrails

Purna refuses, before any GPU is used, to design for chemical-weapon agents or scheduled precursors, controlled substances without a clear research context, known toxin scaffolds, or gain-of-function targets on select agents. If your request is legitimate research and Purna refuses, reach out to your institution’s biosafety officer and contact us.

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When to use enzyme design vs structure prediction

Enzyme design is iterative. Generate 3–5 designs, inspect the Boltz-2 RMSD per design, and prioritise the co-designable ones for experimental expression. Designs with RMSD above 3 Å are not reliable starting points — regenerate with a different seed or adjust the scaffold.
Designed enzymes are computational predictions, not proven catalysts. Plan for experimental characterisation — expression, purification, and activity assays — before treating a design as a working enzyme. The DISCO paper reports that one round of directed evolution on a designed enzyme can deliver several-fold activity improvements.