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Ligand-aware protein sequence design using LigandMPNN. Use this skill when: (1) Designing sequences around small molecules, (2) Enzyme active site design, (3) Ligand binding pocket optimization, (4) Metal coordination site design, (5) Cofactor binding proteins. For standard protein design, use proteinmpnn. For solubility optimization, use solublempnn.
npx skill4agent add adaptyvbio/protein-design-skills ligandmpnn| Requirement | Minimum | Recommended |
|---|---|---|
| Python | 3.8+ | 3.10 |
| CUDA | 11.0+ | 11.7+ |
| GPU VRAM | 8GB | 16GB (T4) |
| RAM | 8GB | 16GB |
First time? See Installation Guide to set up Modal and biomodals.
cd biomodals
modal run modal_ligandmpnn.py \
--pdb-path protein_ligand.pdb \
--num-seq-per-target 16 \
--sampling-temp 0.1git clone https://github.com/dauparas/LigandMPNN.git
cd LigandMPNN
python run.py \
--pdb_path protein_ligand.pdb \
--out_folder output/ \
--num_seq_per_target 16| Parameter | Default | Range | Description |
|---|---|---|---|
| required | path | PDB with ligand |
| 1 | 1-1000 | Sequences per structure |
| "0.1" | "0.0001-1.0" | Temperature (string!) |
| true | bool | Use ligand context |
ATOM ...protein atoms...
HETATM 1 C1 LIG A 999 x.xxx y.yyy z.zzz 1.00 0.00 Coutput/
├── seqs/
│ └── protein.fa # FASTA sequences
└── protein_pdb/
└── protein_0001.pdb # PDBs with designed sequence$ python run.py --pdb_path enzyme_substrate.pdb --out_folder output/ --num_seq_per_target 8
Loading LigandMPNN model weights...
Processing enzyme_substrate.pdb
Found ligand: LIG (12 atoms)
Generated 8 sequences in 3.1 seconds
output/seqs/enzyme_substrate.fa:
>enzyme_substrate_0001, score=1.45, global_score=1.38
MKTAYIAKQRQISFVKSHFSRQLE...
>enzyme_substrate_0002, score=1.52, global_score=1.41
MKTAYIAKQRQISFVKSQFSRQLD...Should I use LigandMPNN?
│
├─ What's in your binding site?
│ ├─ Small molecule / ligand → LigandMPNN ✓
│ ├─ Metal ion (Zn, Fe, etc.) → LigandMPNN ✓
│ ├─ Cofactor (NAD, FAD, ATP) → LigandMPNN ✓
│ ├─ DNA/RNA → LigandMPNN ✓
│ └─ Nothing / protein only → Use ProteinMPNN
│
├─ What type of design?
│ ├─ Enzyme active site → LigandMPNN ✓
│ ├─ Metal binding site → LigandMPNN ✓
│ ├─ Protein-protein binder → Use ProteinMPNN
│ └─ De novo scaffold → Use ProteinMPNN
│
└─ Priority?
├─ Solubility/expression → Consider SolubleMPNN
└─ Ligand context accuracy → LigandMPNN ✓| Campaign Size | Time (T4) | Cost (Modal) | Notes |
|---|---|---|---|
| 100 backbones × 8 seq | 15-20 min | ~$2 | Standard |
| 500 backbones × 8 seq | 1-1.5h | ~$8 | Large campaign |
grep -c "^>" output/seqs/*.fa # Should match backbone_count × num_seq_per_target| Error | Cause | Fix |
|---|---|---|
| Long protein or large batch | Reduce batch_size |
| Ligand not found in PDB | Check HETATM records |
| Empty ligand | Verify ligand has atoms in PDB |
protein-qc